Stem Cell Image of the Week:
Obesity-in-a-dish reveals mutations and abnormal function in nerve cells
Our stem cell image of the week looks like the work of a pre-historic cave dweller who got their hands on some DayGlo paint. But, in fact, it’s a fluorescence microscopy image of stem cell-derived brain cells from the lab of Dhruv Sareen, PhD, at Cedars-Sinai Medical Center. Sareen’s team is investigating the role of the brain in obesity. Since the brain is a not readily accessible organ, the team reprogrammed skin and blood cell samples from severely obese and normal weight individuals into induced pluripotent stem cells (iPSCs). These iPSCs were then matured into nerve cells found in the hypothalamus, an area of the brain that regulates hunger and other functions.
A comparative analysis showed that the nerve cells derived from the obese individuals had several genetic mutations and had an abnormal response to hormones that play a role in telling our brains that we are hungry or full. The Cedars-Sinai team is excited to use this obesity-in-a-dish system to further explore the underlying cellular changes that lead to excessive weight gain. Ultimately, these studies may reveal ways to combat the ever-growing obesity epidemic, as Dr. Sareen states in a press release:
“We are paving the way for personalized medicine, in which drugs could be customized for obese patients with different genetic backgrounds and disease statuses.”
The study was published in Cell Stem Cell
Differences found in stem cells derived from male vs female.
Scientists at UCLA and KU Leuven University in Belgium carried out a study to better understand the molecular mechanisms that control the process of reprogramming adult cells back into the embryonic stem cell-like state of induced pluripotent stem cells (iPSCs). Previous studies have shown that female vs male embryonic stem cells have different patterns of gene regulation. So, in the current study, male and female cells were analyzed side-by-side during the reprogramming process. First author Victor Pasquale explained in a press release that the underlying differences stemmed from the sex chromosomes:
In a normal situation, one of the two X chromosomes in female cells is inactive. But when these cells are reprogrammed into iPS cells, the inactive X becomes active. So, the female iPS cells now have two active X chromosomes, while males have only one. Our results show that studying male and female cells separately is key to a better understanding of how iPS cells are made. And we really need to understand the process if we want to create better disease models and to help the millions of patients waiting for more effective treatments.”
The CIRM-funded study was published in Stem Cell Reports.
Using mini-brains and CRISPR to study genetic linkage of schizophrenia, depression and bipolar disorder.
If you haven’t already picked up on a common thread in this week’s stories, this last entry should make it apparent: iPSC cells are the go-to method to gain insight in the underlying mechanisms of a wide range of biology topics. In this case, researchers at Brigham and Women’s Hospital at Harvard Medical School were interested in understanding how mutations in a gene called DISC1 were linked to several mental illnesses including schizophrenia, bipolar disorder and severe depression. While much has been gleaned from animal models, there’s limited knowledge of how DISC1 affects the development of the human brain.
The team used human iPSCs to grow cerebral organoids, also called mini-brains, which are three-dimensional balls of cells that mimic particular parts of the brain’s anatomy. Using CRISPR-Cas9 gene-editing technology – another very popular research tool – the team introduced DISC1 mutations found in families suffering from these mental disorders.
Compared to cells with normal copies of the DISC1 gene, the mutant organoids showed abnormal structure and excessive cell signaling. When an inhibitor of that cell signaling was added to the growing mutant organoids, the irregular structures did not develop.
These studies using human cells provide an important system for gaining a better understanding of, and potentially treating, mental illnesses that victimize generations of families.
The study was published in Translation Psychiatry and picked up by Eureka Alert.
4 thoughts on “Stem Cell Roundup: The brain & obesity; iPSCs & sex chromosomes; modeling mental illness”
great research , when are these discoveries going to trial
Soon we hope Audrey.
I am wondering if I can requisition a study with TNT tissue nano transfection , which was first online about 2 yrs ago, at OSU with Chandran k. Sen, and now at U OF Indiana. it treats from outside the body with a chip delivering stem cells and or medication that could be used for kidneys , blood supply, and they said more. I have an adrenal adenoma and would like to requisition money to study that application.Is CIRM OUT OF MONEY AND HOW WOULD I AND HOW MUCH WOULD IT COST TO DO A STUDY,/Is there an endocrinologist in CIRM that could do it/ does it have to have NIH status and how long do the studies take. Im going to try exosomes with stem cells to see if it makes a differences suggested in online article about exosomes and tumors. Would I need to site these examples to get attention to this new way of treating from out side the body thank you for your time and attention. ajs
Dear Audrey, I am afraid we don’t do any research here at CIRM, we simply fund it. So we would be unable to help you in your research.