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Hematopoietic stem cells (HSCs) have long been thought to be the ancestors of all blood cells.
After we were born, these pluripotent stem cells produced all of our blood cell lineages: lymphoid cells (lymphoid cell), myeloid cells (myeloid) and erythroid cell.
haemators have long been tracking the presence of HSC in embryos in the hope of reconstructing the process in the lab to provide a therapeutic source of blood cells.
but strangely, in embryos, blood production takes a different form. the first blood cells that appear in
have partially differentiated.
these so-called "targeted progenitors" produce only red and myelin cells, not lymphocyte cells, such as B-cells and T-cells in the immune system.
now, a new study led by George Q. Daley, dean of Harvard Medical School, illustrates the process. researchers at
Daley's lab wanted to know: Is nature deliberately suppressing blood cell pluitorin in early embryonic development? Could this provide clues as to how to restore dupability and more easily produce different blood cell types? To test these ideas, Daley, lead author Linda Vo and their colleagues first used induced pluripotent stem cells (ips cells) in the lab --- adult cells to return to the earliest differentiation stage satiatring--- produce targeted myelo-erythroid progenitors.
they then used short hairpin RNA to inhibit the expression of 20 different proteins one by one to screen for the inhibitory ploritoric factors in these cells.
EZH1: A target for blood cells? As the new study reports, the researchers screened for a protein called EZH1.
when this protein is inhibited, these targeted protocells gain the ability to differentiate into B-cells and T-cells.
they went on to confirm that mouse embryos lacking EZH1 developed HSC earlier and more robustly. further experiments
showed that EZH1 inhibited the expression of genes involved in HSC, lymphocyte production and T-cell activation. "EZH1 provides molecular clues as to how the pluripoterate of embryonic blood progenitor cells is inhibited," said
Daley.
" a team he led recently successfully used ips cells for the first time to produce HSC and other blood progenitor cells.
"these new insights will not only help explain a fascinating challenge in developmental biology, but will also help us transform HSC and T cell populations in vitro.
this may then promote the production of 'off-the-shelf' T-cells for immunotherapy.
"Although we now know how disincentive is inhibited, it remains an open question of how it is inhibited, " he said. "The embryo needs red blood cells to carry oxygen and some myelin cells, but it doesn't need lymphocytes because it depends on the mother's immune system,"
Daley said.
nature is very stingy here.
References: Linda T.Vo, Melissa A. Kinney, Xin Liu et al. Regulation of the pomatopoietic multipotency by EZH1. Nature, Published online: 17 January 2018, doi: 10.1038/nature25435.