JUL 30, 2016 11:06 AM PDT

Toward a Better Understanding of Blood Cell Differentiation

WRITTEN BY: Carmen Leitch
Researchers at ETH Zurich used a cutting edge microscopy technique to investigate how stem cells in the bone marrow produce blood cells. Publishing in Nature, their work challenges long-held beliefs about two proteins that influence that fate.
A simplified overview of normal human hematopoiesis from Wikipedia
There are trillions of cells in the human body, with highly varied functions and characteristics. As cells grow during development, many change from one type to a much more specialized type so they can carry out their functions, in a process called differentiation. Stem cells are less differentiated, and are what gives rise to the various specific cell types. 
 
Stem cells in bone marrow have to make millions of new blood cells every second, because blood cell types have very short lifespans. White blood cells such as leucocytes and blood platelets are only around from a few hours to a couple of days, while red blood cells survive about four months. The stem cells are also multipotent - they can produce many different kinds of blood cells with a range of very different functions; red blood cells transport oxygen while white blood cells play a major role in the immune system. How exactly stem cells are able to differentiate is not well understood, and is a complex process with many players. To learn what we know about the process in blood cells, check out the Khan Academy video below.
The regulation of stem cell differentiation plays a vital role in maintaining the normal process of blood formation,” explained Timm Schroeder, Professor at the ETH Zurich Department of Biosystems Science and Engineering. "If this system starts to malfunction, it can lead to life-threatening diseases such as anemia and leukaemia. We therefore need to have a better understanding of the molecular mechanism involved in this regulation."

There are two proteins - GATA1 and PU.1 - that have been a focus of the research. These proteins are thought to have a critical role in the mechanism of blood cell differentiation. "They are transcription factors capable of activating or disabling comprehensive genetic programs with many target genes. This makes them powerful regulators of cell fates,” said Schroeder. 
 
The researchers used time-lapse microscopy to observe living blood stem cells as they differentiated, with unprecedented accuracy. During this process, the investigators also quantified the GATA1 and PU.1 proteins to try to elucidate more about their role. Rather than using a pool of cells that could contain dead cells or obscure differences between cells, they monitored cells individually.
A screenshot of a video that accompanied their publication which displayed their monitoring of single cells. / Credit: Nature
Measuring the GATA1 and PU.1 proteins in single cells enabled the researchers to see that those proteins are not central players in blood cell differentiation. "For decades it was thought that these two transcription factors were responsible for making the lineage decisions for stem cells. Now we are able to show that this is not the case, but that other mechanisms must be responsible for these decisions", explains Professor Schroeder. 

Future research must now interrogate alternative molecular mechanisms to understand more about the incredibly complicated mode of blood stem cell differentiation, and to potentially help those suffering with blood cell diseases.

Sources: AAAS/Eurekalert! via ETH Zurich, NIH, Nature
About the Author
BS
Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
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