Scientists have reported new discoveries about how haematopoietic stem cells diversify in the early embryo.
Haematopoietic stem and progenitor cells (HSPCs) in the adult bone marrow are diverse, and produce a number of different cell lineages. This diversity is apparent in embryos, where HSPCs are generated from endothelial cells. However, to date it has not been clear how these intrinsic differences are acquired.
A team led by Dr Stefania Nicoli of Yale School of Medicine, New Haven, USA, carried out tests on zebrafish and found that the diversity of early blood stem cells is in part controlled by a molecule called microRNA 128.
When microRNA 128 was removed from the zebrafish embryos before cells were made, the resulting HSPCs were skewed towards producing erythroid or lymphoid lineages.
This had “long-term consequences on the respective blood lineages,” they report.
The findings suggest that different types of blood stem cells were determined very early in development. “And each of us maintain this level of diversity through adulthood,” said Dr Nicoli. “This varying level of blood stem cell diversity can be ‘programmed’ and may help to change susceptibility to cardiovascular and immune diseases.
“The findings are quite powerful.”
With this new finding, the team believe that the ability to manipulate stem cell populations will become more important in health care. For example, the research may eventually lead to a more diverse and balanced production of blood stem cells ex vivo, improving outcomes for blood cancer patients.
Ghersi JJ, Baldissera G, Hintzen J, Luff SA, Cheng S, Xia IF, Sturgeon CM, Nicoli S. (2023) “Haematopoietic stem and progenitor cell heterogeneity is inherited from the embryonic endothelium.” Nature Cell Biology, doi: 10.1038/s41556-023-01187-9
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