Stem Cell Roundup: Knowing the nose, stem cell stress and cell fate math.

The Stem Cellar’s Image of the Week.
Our favorite image this week, comes to us from researchers at Washington University School of Medicine in St. Louis. Looking like a psychedelic Rorschach test, the fluorescence microscopy depicts mouse olfactory epithelium (in green), a sheet of tissue that develops in the nose. The team identified a new stem cell type that controls the growth of this tissue. New insights from the study of these cells could help the team better understand why some animals, like dogs, have a far superior sense of smell than humans.

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Peering into the nasal cavity of a mouse. Olfactory epithelium is indicated by green. Image credit: Lu Yang, Washington University School of Medicine in St. Louis.

A Washington U. press release provides more details about this fascinating study which appears in Developmental Cell.

How stress affects blood-forming stem cells.
Stress affects all of us in different ways. Some people handle it well. Some crack up and become nervous wrecks. So, perhaps it shouldn’t come as a huge surprise that stress also affects some stem cells. What is a pleasant surprise is that knowing this could help people undergoing cancer therapy or bone marrow transplants.

First a bit of background. Hematopoietic, or blood-forming stem cells (HSCs) come from bone marrow and are supported by other cells that secrete growth factors, including one called pleiotrophin or PTN. While researchers knew PTN was present in bone marrow they weren’t sure precisely what role it played.

So, researchers at UCLA set out to discover what PTN did.

In a CIRM-funded study they took mice that lacked PTN in endothelial cells – these line the blood vessels – or in their stromal cells – which make up the connective tissue. They found that a lack of PTN in stromal cells caused a lack of blood stem cells, but a lack of PTN in endothelial cells had no impact.

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Expression of pleiotrophin (green) in bone marrow blood vessels (red) and stromal cells (white) is shown in normal mice (left) and in mice at 24 hours following irradiation (right). Image credit: UCLA

However, as Dr. John Chute explained in a news release, when they stressed the cells, by exposing them to radiation, they found something very different:

“The surprising finding was that pleiotrophin from stromal cells was not necessary for blood stem cell regeneration following irradiation — but pleiotrophin from endothelial cells was necessary.”

In other words, during normal times the stem cells rely on PTN from stromal cells, but after stress they depend on PTN from endothelial cells.

Dr. Chute says, because treatments like chemotherapy and radiation deplete bone marrow stem cells, this finding could have real-world implications for patients.

“These therapies for cancer patients suppress our blood cell systems over time. It may be possible to administer modified, recombinant versions of pleiotrophin to patients to accelerate blood cell regeneration. This strategy also may apply to patients undergoing bone marrow transplants.”

The study appears in the journal Cell Stem Cell.

Predicting the fate of cells with math
Researchers at Harvard Medical School and the Karolinska Institutet in Sweden reported this week that they have devised a mathematical model that can predict the fate of stem cells in the brain.

It may sound like science-fiction but the accomplished the feat by tracking changes in messenger RNA (mRNA), the genetic molecule that translates our DNA code into instructions for building proteins. As a brain stem cell begins specializing into specific cell types, hundreds of genes get turns on and off, which is observed by the rate of changes in mRNA productions.

The team built their predictive model by measuring these changes. In a press release, co-senior author, Harvard professor Peter Kharchenko, described this process using a great analogy:

“Estimating RNA velocity—or the rate of RNA change over time—is akin to observing the cooks in a restaurant kitchen as they line up the ingredients to figure out what dishes they’ll be serving up next.”

The team verified their mathematical model by inputting other data that was not use in constructing the model. Karolinkska Institutet professor, Sten Linnarsson, the other co-senior author on the study, described how such a model could be applied to human biomedical research:

“RNA velocity shows in detail how neurons and other cells acquire their specific functions as the brain develops and matures. We’re especially excited that this new method promises to help reveal how brains normally develop, but also to provide clues as to what goes wrong in human disorders of brain development, such as schizophrenia and autism.”

The study appears in the journal Nature.

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