UCLA Scientists Find 3000 New Genes in “Junk DNA” of Immune Stem Cells

Genes and Junk

Do you remember learning about Junk DNA when you took Biology in high school? The term was used to described 98% of the human genome that doesn’t make up its approximately 22,000 genes. We used to think that Junk DNA didn’t serve a purpose, but that was before we discovered special elements called non-coding RNAs that call Junk DNA their home. But we’re getting ahead of ourselves, so let’s take a step back.

Genes are sequences of DNA that contain the blueprints for the proteins that make your cells and organs function. Before a gene can become a protein, its transformed into a molecule called an RNA. RNAs contain messages that tell a cell’s machinery what types of protein to make and how many.

Not Junk After All

Now back to “Junk DNA”… scientists thought that because this mass of DNA sequences was never turned into protein, it served no purpose. It turns out that they couldn’t be farther from the facts.

There are actually sequences of DNA in our genomes that are blueprints for RNAs that never become proteins. Scientists call them “non-coding” RNAs, and they play very important roles in the body such as replicating DNA and regulating gene expression – deciding which genes are turned on and which are turned off.

Another important function that non-coding RNAs control is cell differentiation, or the maturation of immature cells into adult cells. Differentiation is a complicated process, and because non-coding RNAs are relatively new to the scientific world, we haven’t figured out their exact roles in the differentiation of stem cells into adult cells.

Understanding Immune Cell Development

In a study published this week in Nature Immunology, UCLA scientists reported the discovery of 3000 new genes that make a type of non-coding RNA called a long non-coding RNA (lncRNA) that regulates the differentiation of stem cells into mature immune cells like B and T cells, which play a key role in fighting infection. This important study was funded in part by CIRM.

UCLA scientists David Casero and Gay Crooks with the sequencing machine that separated the genetic information within the bone marrow and thymus gland tissue stem cells. (Image credit: Mirabai Vogt-James, UCLA Broad Stem Cell Research Center)

UCLA scientists David Casero and Gay Crooks with the sequencing machine used to identify the 3000 new genes. (Image credit: Mirabai Vogt-James, UCLA Broad Stem Cell Research Center)

Using sequencing technology and bioinformatics, they mapped the RNA landscape (known as the transcriptome) of rare stem cells isolated from human bone marrow (hematopoietic stem cells) and the thymus (lymphoid progenitor cells). They identified over 9000 genes that produced lncRNAs that were important for moderating various stages of immune cell development. Of this number, over 3000 were genes whose lncRNAs hadn’t been found before.

First author, David Casero explained the importance of their discovery in a UCLA press release:

Our findings are exciting because they provide a huge and unique resource for the whole immunology community. We will now be able to drill down on the specific LncRNA genes that seem to be most important at each stage of immune cell development and understand how they function individually and together to control the process.


Co-senior author and UCLA professor Gay Crooks explained that the goal of their work was to gain a better understanding of how the immune system develops in order to battle serious diseases that affect it and open up avenues for generating better cell therapies.

If we can understand how the immune system is generated and maintained during life, we can find ways to improve production of immune cells for potential therapies after chemotherapy, radiation and bone marrow transplant, or for patients with HIV and inherited immune deficiencies. In addition, by understanding the genes that control this process we can better understand how they are changed in cancers like leukemia and lymphoma.


Final Words

While this study focused on the role of lncRNAs in the development of the immune system and the differentiation of immune stem cells, the technology in this study can be used to understand the development of other systems and organs.

Scientists are already publishing papers on the role of lncRNAs in the differentiation of stem cells in the brain and heart, and further work in this field will undoubtedly uncover many new and important lncRNA genes. If the pace keeps up, the term “Junk DNA” will need to be retired to the junk yard.


Image source www.biocomicals.com

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Stem cells and prostate cancer are more similar than we thought

Prostate cancer is a scary word for men, no matter how macho or healthy they are. These days however, prostate cancer is no longer a death sentence for them. In fact, many men survive this disease if diagnosed early. However, for those unlucky ones who have more advanced stages of prostate cancer (where the tumor has metastasized and spread to other organs), the typical treatments used to fight the tumors don’t work effectively because advanced tumors become resistant to these therapies.

To help those afflicted with late stage prostate cancer, scientists are trying to understand the nature of prostate cancer cells and what makes them so “deadly”. By understanding the biology behind these tumor cells, they hope to develop better therapies to treat the late-stage forms of this disease.

UCLA scientists Bryan Smith and Owen Witte. (Image credit: UCLA Broad Stem Cell Research Center)

UCLA scientists Bryan Smith and Owen Witte. (Image credit: UCLA Broad Stem Cell Research Center)

But don’t worry, help is already on its way. Two groups from the University of California, Los Angeles and the University of California, Santa Cruz published a breakthrough discovery yesterday on the similarity between prostate cancer cells and prostate stem cells. The study was published in the journal PNAS and was led by senior author and director of the UCLA Broad Stem Cell Research Center, Dr. Owen Witte.

Using bioinformatics, Witte and his team compared the gene expression profiles of late-stage, metastatic prostate cancer cells sourced from tumor biopsies of living patients to healthy cell types in the male prostate. Epithelial cells are one of the main cell types in the prostate (they form the prostate glands) and they come in two forms: basal and luminal. When they compared the gene expression profiles of the prostate cancer cells to healthy prostate epithelial cells, they found that the cancer cells had a similar profile to normal prostate epithelial basal stem cells.

Image of a prostate cancer tumor. Green and red represent different stem cell traits and the yellow areas show where two stem cell traits are expressed together. (Image credit: UCLA Broad Stem Cell Research Center)

Image of a prostate cancer tumor. Green and red represent different stem cell traits and the yellow areas show where two stem cell traits are expressed together. (Image credit: UCLA Broad Stem Cell Research Center)

In fact, they discovered a 91-gene signature specific to the basal stem cells in the prostate. This profile included genes important for stem cell signaling and invasiveness. That meant that the metastatic prostate cancer cells also expressed “stem-like” genes.

First author Bryan Smith explained how their results support similar findings for other types of cancers. “Evidence from cancer research suggests that aggressive cancers have stem–cell-like traits. We now know this to be true for the most aggressive form of prostate cancer.”

So what does this study mean for prostate cancer patients? I’ll let Dr. Witte answer this one…

Treatments for early stage prostate cancer are often successful, but therapies that target the more aggressive and late-stage forms of the disease are urgently needed. I believe this research gives us important insight into the cellular nature of aggressive prostate cancer. Pinpointing the cellular traits of cancer — what makes those cells grow and spread — is crucial because then we can possibly target those traits to reverse or stop cancer’s progression. Our findings will inform our work as we strive to find treatments for aggressive prostate cancer.

Related links:


CIRM scholar Ke Wei talks heart regeneration

Ke Wei

Ke Wei

“How do you mend a broken heart?” was the topic of one of our recent Stem Cellar blogs highlighting a stellar CIRM-funded publication on the regenerative abilities of the protein FSTL1 following heart injury. One of the master-minds behind this study is co-first author Ke Wei. Ke is a postdoc in Dr. Mark Mercola’s lab at the Sanford Burnham Prebys Medical Discovery Institute located in balmy southern California. He also happens to be one of our prized CIRM scholars.


Cross sections of a healthy (control) or injured mouse heart. Injured hearts treated with patches containing FSTL1 show the most recovery of healthy heart tissue (red). Image adapted from Wei et al. 2015)

Upon hearing of Ke’s important and exciting accomplishments in the field of regenerative medicine for heart disease, we called him up to learn more about his scientific accomplishments and aspirations.

Q: Tell us about your research background and how you got into this field?

KW: I went to UCLA for my graduate school PhD, and I studied under Dr. Fabian Chen focusing on heart development. At that time, I mainly worked on very early heart development and other tissues like smooth muscle cells. For my graduate thesis work, I found that particular genes were important for smooth muscle development.

So I was trained as a heart developmental biologist, but after my PhD, I came to the Burnham Institute and I joined two labs: Dr. Mark Mercola and Dr. Pilar Ruiz-Lozano. They co-mentored me for the first couple of years of my postdoc. Mark is interested in using stem cells and high throughput screens to identify pharmaceutical compounds for inducing heart regeneration and treating heart diseases. Pilar is interested in the epicardium, the outer layer of the heart, which is known to play important roles during heart development. When I joined their labs, they had combined forces to study how the epicardium affects heart development and heart diseases.

In their labs, I used my developmental biologist background to combine in vitro stem cells based screening studies (Mark) and in vivo mouse embryonic heart development studies (Pilar) to dissect the function of the epicardium on heart development and disease.

Q: Tell us about your experience as a CIRM scholar and what you were able to accomplish.

KW: My two years of CIRM fellowship were separated but my focus was the same for both CIRM-funded periods: to understand the effect of the epicardium on heart development and diseases.

In my first project in 2008, we tried to generate an in vitro model of mouse epicardial cells and used those cells to study their influence on cardiac differentiation using both in vitro and in vivo experiments. We ran into a lot of technical difficulties, so at that time, we decided to switch to using existing in vitro epicardial cell lines, and using those to study their influence on cardiomyocytes (heart muscle cells).

In my second year of CIRM funding in 2011, we identified the genes and proteins that can promote immature cardiomyocytes to proliferate, and put them in vivo and it worked. So the success of our publication all started from my second year of CIRM-fellowship.

Q: What benefits did you experience as a CIRM scholar?

KW: I’ve really enjoyed being a CIRM scholar and took advantage of the resources they provided me over the years. One of the benefits I enjoyed the most was attending the CIRM annual meetings and retreats. I was able to talk with a lot of scientists with different backgrounds, and that really expanded my horizons.

As you can see from our paper in Nature, it’s definitely not only a developmental biologist paper. It’s actually very clinical and collaborative, and it was done by many different groups working together. By going to CIRM conferences and meeting all the other CIRM fellows, I got a lot of new ideas, and those ideas encouraged me to collaborate with more scientists. These events really encouraged me to look beyond the thoughts of a developmental biologist.

Our paper is co-authored by me and Vahid Serpooshan from Stanford. We co-first authored this paper, and my work mainly involved the in vitro studies that identified the regenerative proteins and their function in heart injury. Vahid’s approach was more bioengineering focused. He produced the FSTL1 patch, put it in the rodent heart, and conducted all the other in vivo studies. It was a perfect collaboration to push this project for publication in a high level journal like Nature.

Q: What is the big picture of your research and your future goals?

KW: I plan to stay in academia. The key thing about heart diseases is that heart regeneration is very limited. Using our approach, we found one particular protein that’s important to the regenerative process, and in reality, its concentration is very low in the heart when it’s infarcted (injured). I think we have set up a pretty good system to test all possible therapeutic means in the lab, including proteins from the epicardium, small molecules, microRNAs and other compounds to activate cardiomyocyte proliferation. I plan to focus on understanding the mechanisms for why cardiomyocytes stop proliferating in the adult heart, and what new approaches we can pursue to promote their expansion and regenerative abilities. The FSTL1 story is the start of this, and I will try to find new factors that can promote heart regeneration.

Q: Will your work involve human stem cell models?

KW: To make this study clinically relevant, we included the swine models. We are definitely testing FSTL1 in human cells right now. Currently we can produce a huge amount of the human cardiomyocytes. They seem to be at a different stage than rodent cells so we are optimizing the system to perform screens for human cell proliferation. When that system is set up, then anything that comes out of the screen will be much more relevant to clinical studies in humans.

Q: What is your favorite thing about being a scientist?

Knowing that the information I acquire through experiments is new to mankind, and that my actions expand the horizon of combined human knowledge, even just for a tiny bit, is a huge satisfaction to me as a scientist.

Protein Revs Up Bone Stem Cells; Points Toward Future Osteoporosis Drug

Take a moment to feel your arm and wrist bones. They’re a lot more like solid rock than the soft stretchy skin that covers them. But bone is very much a living tissue continually being broken down and built back up in a process called bone remodeling. In people with osteoporosis, this balance tips toward bone breakdown leading to more porous, fragile bones with increased risk of fractures. An estimated ten million people in the U.S. have osteoporosis accounting for 1.5 million fractures annually at a cost of $17 billion in medical care, not to mention the emotional toll of these often debilitating and even life threatening injuries.

Fluorescent imaging mouse spines. Treatment with NELL-1 (right) shows greater bone formation compared to untreated mice (left). Credit: Broad Stem Cell Research Center

Fluorescent imaging of mouse spines. Treatment with NELL-1 (right) shows greater bone formation compared to untreated mice (left). Credit: Broad Stem Cell Research Center

This week a CIRM-funded research team at UCLA reported in Nature Communications that injection of a human protein called NELL-1 into the blood of mice with osteoporosis-like symptoms tipped the balance back toward bone formation. In a large animal study, delivering NELL-1 directly into the spine also led to increased bone volume. In a university press release, co-senior author Kang Ting spoke of his hopes that these results open up a new therapeutic avenue for treating osteoporosis and other ailments:

“Our end goal is really to harness the bone forming properties of NELL-1 to better treat patients with diverse causes of bone loss, from trauma in military personnel to osteoporosis from age, disease or very weak gravity, which causes bone loss in astronauts.”

In petri dish experiments leading up to these animal results, the research team showed that NELL-1 acts by increasing the specialization of mesenchymal stem cells – a type of adult stem cell found in the bone marrow and fat – into osteoblasts, the cells responsible for building new bone. At the same time, NELL-1 reduced the generation of osteoclasts, the cells responsible for the breakdown, or resorption, of bone. This dual action of NELL-1 explains how it improved the osteoporosis-like symptoms in the animals. Check out this fascinating animation for a visual description of osteoblasts and osteoclasts:

Many of the other molecules that promote bone growth aren’t as efficient as NELL-1: while they increase osteoblast numbers they also increase osteoclasts to some extent. For example, Fosamax is a drug prescribed to women with osteoporosis to help build stronger bones but long-term use has been associated with even more brittle bones and fractures. So this finding with NELL-1 sets it apart and hints at fewer side effects as a therapeutic. Still, it’s known to play a role in brain, cartilage, and blood vessel development so careful studies of non-bone effects are needed as the team pursues a road to the clinic.

For more information about CIRM-funded projects related to osteoporosis, visit our online fact sheet.

New Video: Defeating Sickle Cell Disease with Stem Cells + Gene Therapy

Suffering with an incurable illness is no laughing matter. But last year when we debuted the pilot episode of Stem Cells in Your Face, a lighthearted video series that describes specific diseases and explains the latest progress in stem cell-based therapies, we hoped that a mix of science and humor would help make the information stick in the minds of our viewers. We were thrilled, based on your comments, that you enjoyed watching Treating ALS with a Disease in a Dish as much as we enjoyed producing it and that you wanted to see more:

“Very informative yet easy to understand pilot episode! Hope to see more in this series soon!” “Might I suggest highlighting a different disease CIRM focuses on in each video?”

Ask and you shall receive. This week we’ve posted the second installment: Defeating Sickle Cell Disease with Stem Cells + Jean Gene Therapy which is being rolled out as a companion piece to our new blog feature series, Genes + Cells.

 The video highlights a CIRM-funded clinical trial at UCLA that is testing a stem cell and gene therapy treatment for sickle cell disease. This awful genetic disorder causes red blood cells to assume a sickle shape, clogging blood vessels and producing episodes of excruciating pain, called crises, and leading to progressive organ damage. By twenty years of age about 15 percent of people with sickle cell disease have had major strokes and by 40 almost half of the patients have significant mental dysfunction. The disease strikes one in 500 African Americans and 1 in 36,000 Hispanic people. A standard treatment for sickle cell disease is a blood transfusion but the benefits are short-lived and require repeated procedures. Bone marrow transplants can be curative but they require a well-matched blood donor which is hard to find and can still be very risky. The UCLA team, on the other hand, aims to correct the sickle cell genetic mutation within the blood stem cells of the patient, which in theory could provide a life-long supply of normal shaped red blood cells. Don Kohn, the lead scientist on the team, explains their strategy in the video:

“The approach that we’re looking at would be to take the patient’s own bone marrow, isolate the [blood] stem cells, in the laboratory put in the gene we’ve been working on that prevents the red blood cells from sickling. So transplanting their own bone marrow back to them in theory should be safe, we don’t have to worry about rejection.“

If all goes well, sickle cell disease may soon be a thing of the past. As patient advocate Adrienne Shapiro has so eloquently stated in a previous Stories of Hope blog post:

“It’s my true belief that I’m going to be the last woman in my family to have a child with sickle cell disease. My afflicted daughter is going to be the last child to suffer, and my other daughter [who does not have the disease but carries the sickle cell mutation] is going to be the last one to fear [passing on the disease to her children]. Stem cells are going to fix this for us and many other families.”

This clinical trial represents one of the first trials to be part of CIRM’s Alpha Stem Cell Network. To learn more, visit our Alpha Clinic webpage. And for more details about CIRM-funding of sickle cell disease research visit these pages:

CIRM-Funded Scientists Build a Better Neuron; Gain New Insight into Motor Neuron Disease

Each individual muscle in our body—no matter how large or how small—is controlled by several types of motor neurons. Damage to one or more types of these neurons can give rise to some of the most devastating motor neuron diseases, many of which have no cure. But now, stem cell scientists at UCLA have manufactured a way to efficiently generate motor neuron subtypes from stem cells, thus providing an improved system with which to study these crucial cells.

“Motor neuron diseases are complex and have no cure; currently we can only provide limited treatments that help patients with some symptoms,” said senior author Bennett Novitch, in a news release. “The results from our study present an effective approach for generating specific motor neuron populations from embryonic stem cells to enhance our understanding of motor neuron development and disease.”

Normally, motor neurons work by transmitting signals between the brain and the body’s muscles. When that connection is severed, the individual loses the ability to control individual muscle movement. This is what happens in the case of amyotrophic lateral sclerosis, or ALS, also known as Lou Gehrig’s disease.

These images reveal the significance of the 'Foxp1 effect.' The Foxp1 transcription factor is crucial to the normal growth and function of motor neurons involved in limb-movement.

These images reveal the significance of the ‘Foxp1 effect.’ The Foxp1 transcription factor is crucial to the normal growth and function of motor neurons involved in limb-movement.

Recent efforts had focused on ways to use stem cell biology to grow motor neurons in the lab. However, such efforts to generate a specific type of motor neuron, called limb-innervating motor neurons, have not been successful. This motor-neuron subtype is particularly affected in ALS, as it supplies nerves to the arms and legs—the regions usually most affected by this deadly disease.

In this study, published this week in Nature Communications, Novitch and his team, including first author Katrina Adams, worked to develop a better method to produce limb-innervating motor neurons. Previous efforts had only had a success rate of about 3 percent. But Novitch and Adams were able to boost that number five-fold, to 20 percent.

Specifically, the UCLA team—using both mouse and human embryonic stem cells—used a technique called ‘transcriptional programming,’ in order to coax these stem cells into become fully functional, limb-innervating motor neurons.

In this approach, which was funded in part by a grant from CIRM, the team added a single transcription factor (a type of protein that regulates gene function), which would then guide the stem cell towards becoming the right type of motor neuron. Here, Novitch, Adams and the team used the Foxp1 transcription factor to do the job.

Normally, Foxp1 is found in healthy, functioning limb-innervating motor neurons. But in stem cell-derived motor neurons, Foxp1 was missing. So the team reasoned that Foxp1 might actually be the key factor to successfully growing these neurons.

Their initial tests of this theory, in which they inserted Foxp1 into a developing chicken spinal cord (a widely used model for neurological research), were far more successful. This result, which is not usually seen with most unmodified stem-cell-derived motor neurons, illustrates the important role played by Foxp1.

The most immediate implications of this research is that now scientists can now use this method to conduct more robust studies that enhance the understanding of how these cells work and, importantly, what happens when things go awry.

One-Time, Lasting Treatment for Sickle Cell Disease May be on Horizon, According to New CIRM-Funded Study

For the nearly 1,000 babies born each year in the United States with sickle cell disease, a painful and arduous road awaits them. The only cure is to find a bone marrow donor—an exceedingly rare proposition. Instead, the standard treatment for this inherited blood disorder is regular blood transfusions, with repeated hospitalizations to deal with complications of the disease. And even then, life expectancy is less than 40 years old.

In Sickle Cell Disease, the misshapen red blood cells cause painful blood clots and a host of other complications.

In Sickle Cell Disease, the misshapen red blood cells cause painful blood clots and a host of other complications.

But now, scientists at UCLA are offering up a potentially superior alternative: a new method of gene therapy that can correct the genetic mutation that causes sickle cell disease—and thus help the body on its way to generate normal, healthy blood cells for the rest of the patient’s life. The study, funded in part by CIRM and reported in the journal Blood, offers a great alternative to developing a functional cure for sickle cell disease. The UCLA team is about to begin a clinical trial with another gene therapy method, so they—and their patients—will now have two shots on goal in their effort to cure the disease.

Though sickle cell disease causes dangerous changes to a patient’s entire blood supply, it is caused by one single genetic mutation in the beta-globin gene—altering the shape of the red blood cells from round and soft to pointed and hard, thus resembling a ‘sickle’ shape for which the disease is named. But the UCLA team, led by Donald Kohn, has now developed two methods that can correct the harmful mutation. As he explained in a UCLA news release about the newest technique:

“[These results] suggest the future direction for treating genetic diseases will be by correcting the specific mutation in a patient’s genetic code. Since sickle cell disease was the first human genetic disease where we understood the fundamental gene defect, and since everyone with sickle cell has the exact same mutation in the beta-globin gene, it is a great target for this gene correction method.”

The latest gene correction technique used by the team uses special enzymes, called zinc-finger nucleases, to literally cut out and remove the harmful mutation, replacing it with a corrected version. Here, Kohn and his team collected bone marrow stem cells from individuals with sickle cell disease. These bone marrow stem cells would normally give rise to sickle-shaped red blood cells. But in this study, the team zapped them with the zinc-finger nucleases in order to correct the mutation.

Then, the researchers implanted these corrected cells into laboratory mice. Much to their amazement, the implanted cells began to replicate—into normal, healthy red blood cells.

Kohn and his team worked with Sangamo BioSciences, Inc. to design the zinc-finger nucleases that specifically targeted and cut the sickle-cell mutation. The next steps will involve improving the efficiency and safest of this method in pre-clinical animal models, before moving into clinical trials.

“This is a promising first step in showing that gene correction has the potential to help patients with sickle cell disease,” said UCLA graduate student Megan Hoban, the study’s first author. “The study data provide the foundational evidence that the method is viable.”

This isn’t the first disease for which Kohn’s team has made significant strides in gene therapy to cure blood disorders. Just last year, the team announced a promising clinical trial to cure Severe Combined Immunodeficiency Syndrome, also known as SCID or “Bubble Baby Disease,” by correcting the genetic mutation that causes it.

While this current study still requires more research before moving into clinical trials, Kohn and his team announced last month that their other gene therapy method, also funded by CIRM, has been approved to start clinical trials. Kohn argues that it’s vital to explore all promising treatment options for this devastating condition:

“Finding varied ways to conduct stem cell gene therapies is important because not every treatment will work for every patient. Both methods could end up being viable approaches to providing one-time, lasting treatments for sickle cell disease and could also be applied to the treatment of a large number of other genetic diseases.”

Find Out More:
Read first-hand about Sickle Cell Disease in our Stories of Hope series.
Watch Donald Kohn speak to CIRM’s governing Board about his research.

Scientists Send Rodents to Space; Test New Therapy to Prevent Bone Loss

In just a few months, 40 very special rodents will embark upon the journey of a lifetime.


Today UCLA scientists are announcing the start of a project that will test a new therapy that has the potential to slow, halt or even reverse bone loss due to disease or injury.

With grant funding from the Center for the Advancement of Science in Space (CASIS), a team of stem cell scientists led by UCLA professor of orthopedic surgery Chia Soo will send 40 rodents to the International Space Station (ISS). Living under microgravity conditions for two months, these rodents will begin to undergo bone loss—thus closely mimicking the conditions of bone loss, known as osteoporosis, seen in humans back on Earth.

At that point, the rodents will be injected with a molecule called NELL-1. Discovered by Soo’s UCLA colleague Kang Ting, this molecule has been shown in early tests to spur bone growth. In this new set of experiments on the ISS, the researchers hope to test the ability of NELL-1 to spur bone growth in the rodents.

The team is optimistic that NELL-1 could really be key to transforming how doctors treat bone loss. Said Ting in a news release:

“NELL-1 holds tremendous hope, not only for preventing bone loss but one day even restoring healthy bone. For patients who are bed-bound and suffering from bone loss, it could be life-changing.”

“Besides testing the limits of NELL-1’s robust bone-producing efforts, this mission will provide new insights about bone biology and could uncover important clues for curing diseases such as osteoporosis,” added Ben Wu, a UCLA bioengineer responsible for initially modifying NELL-1 to make it useful for treating bone loss.

The UCLA team will oversee ground operations while the experiments will be performed by NASA scientists on the ISS and coordinated by CASIS.

These experiments are important not only for developing new therapies to treat gradual bone loss, such as osteoporosis, which normally affects the elderly, but also those who have bone loss due to trauma or injury—including bone loss due to extended microgravity conditions, a persistent problem for astronauts living on the ISS. Said Soo:

“This research has enormous translational application for astronauts in space flight and for patients on Earth who have osteoporosis or other bone-loss problems from disease, illness or trauma.”

CIRM-funded scientists track the steps that take an adult cell back in time

The ability to transform an adult cell back into a stem cell has been heralded as one of the greatest achievements of the 21st century. Scientists have lauded this discovery, made by Nobel Prize-winning scientist Shinya Yamanaka, as a game changer for the future of medicine.

Despite this extraordinary advance, the method remains inefficient. And even the top experts still don’t quite understand how it works.

But now, a team of stem cell scientists from the University of California, Los Angeles (UCLA) has mapped the precise series of steps that an adult skin cell must go through to become a stem cell. The results, published online in the journal Cell, represent a much-needed step towards bringing cellular reprogramming forward.

A colony of iPSC's obtained by reprogramming a specialized cell for two weeks. The starting specialized cells can only make more of themselves, while the reprogrammed cells obtained from them can give rise to all cells of the body.

A colony of iPSC’s obtained by reprogramming a specialized cell for two weeks. The starting specialized cells can only make more of themselves, while the reprogrammed cells obtained from them can give rise to all cells of the body.

In this study, co-first authors Vincent Pasque and Jason Tchieu initiated the reprogramming process, whereby adult cells are reprogrammed back into embryonic-like stem cells. Yamanaka called these cells induced pluripotent stem cells, or iPSCs.

In order to map the steps being taken to reprogram these cells, the team devised a detailed time-course analysis whereby they would observe and analyze the cells each day as they transformed over a period of two weeks.

Importantly, the team found that no matter what type of adult cells were involved, the specific steps it took during reprogramming were the same. This revelation, that all adult cell types follow the same road map, is one of the most exciting discoveries. Said Pasque in a news release:

“The exact stage of reprogramming of any cell can now be determined. This study signals a big change in our thinking, because it provides simple and efficient tools for scientists to study stem cell creation in a stage-by-stage manner.”

The research team, led by CIRM grantee Katherin Plath, also uncovered some interesting information about the sequence of steps taken by these reprogrammed cells.

When an adult cell is reprogrammed back into an iPSC, it is not simply that all the steps that normally take an embryonic stem cell into an adult cell are reversed. Some may be reversed in the correct order, but others are not. And some steps are put off until the very end—indicating strong resistance against reprogramming.

“This reflects how cells do not like to change from one specialized cell type into another and resist a change in cellular identity,” said Pasque.

With future work, the team hopes to continue to investigate the reprogramming process. They are also hopeful that this newfound insight will bring robust iPSC-based therapies to the clinic.

A look at 2014: some of the lowlights of stem cell research this past year

It’s been quite a year in stem cell research. Here at the stem cell agency eight projects that we are funding have been approved for clinical trials and several more hope to get approval in early 2015. And Dr. Don Kohn and his team at UCLA announced that they have effectively cured Severe Combined Immunodeficiency or SCID  a fatal disease that leaves infants with no immune system.

But the news hasn’t been all good. A number of high profile retractions of studies published in prestigious journals have drawn attention to some of the less lovely aspects of science. There are many reasons why a researcher or scientific journal decides to retract a study – falsified data, inability of others to reproduce the findings etc. – but the end result is always the same, a stain on the reputation of science in general.

Of course the only thing worse than a retraction is bad science that is not retracted. That’s why websites such as Retraction Watch are so important. They keep an eye on the field and help draw attention to questionable papers (in all areas of science, not just stem cell research).

Ivan Oransky of Retraction Watch

Ivan Oransky of Retraction Watch

The two founders of the site, Evan Marcus and Ivan Oransky, do a remarkable job of highlighting work that doesn’t stand up to closer scrutiny. This year they worked with the magazine Science to highlight The Top 10 Retractions of 2014.  Sadly, two of the top 10 – including the number one story of the year – concern stem cell research.

The list is a reminder, as we look forward to 2015 for more progress in the field, that we need to always check the credibility of studies or sources we are using. Sometimes something that seems too good to be true, is too good to be true.

Tomorrow, we’ll take a look at the flip side of this discussion, the “Biggest Scientific Breakthroughs of 2014”. It’s always good to end the year on a positive note.