The road not taken?

Hematopoietic defects in response to reduced Arhgap21

“…Analysis of the erythroid and megakaryocytic lineages in Arhgap21 +/− bone marrow indicated a reduced number of erythroid progenitors (BFU-E in colony formation and ErP by flow cytometry) along with increased frequency of MkP and megakaryocytic-committed (CD41 + ) cells, suggesting that the downregulation of Arhgap21 could bias the MEP fate decision toward the megakaryocytic lineage. In order to test this observation, one needs to evaluate a truly bipotent MEP in assays with single cell resolution, but with high capacity so that hundreds of cells can be assayed simultaneously to assess not only the fate decision of this purified population, but also the molecular mechanisms on which their function relies ( Narla & Mohandas, 2016 ; Sanada et al, 2016 ). Taking advantage of our recently published strategies to enrich for human MEP, MkP and ErP ( Sanada et al, 2016 ) along with the development of a novel assay to quantify at the single cell level the MEP fate decision, our hypothesis of a Mk-biased MEP under Arhgap21 inhibition in mice was confirmed in human primary cells.…”

“…Hematopoietic stem and progenitor cells (HSPCs) are constantly undergoing fate-decisions, including quiescence vs. proliferation, self-renewal vs. differentiation, lineage commitment, and mobilization vs. adhesion. These processes are regulated by growth factors, cell-cell interactions, transcriptional networks, and epigenetics, many of which lead to cytoskeletal rearrangements ( Nayak et al, 2013 ; Narla & Mohandas, 2016 ).…”