Although bone marrow (BM) niche cells are essential for hematopoietic stem cell (HSC) maintenance, their interaction in response to stress is not well defined. Here, we used a mouse model of acute thrombocytopenia to investigate the crosstalk between HSCs and niche cells during restoration of the thrombocyte pool. This process required membrane-localized stem cell factor (m-SCF) in megakaryocytes, which was regulated by vascular endothelial growth factor A (VEGF-A) and platelet-derived growth factor-B (PDGF-B) derived from BM endothelial cells. HSCs and multipotent progenitors 2 (MPP2), but not MPP3/4 were subsequently activated by a dual receptor tyrosine kinase (RTK)-dependent signaling event, namely m-SCF/c-Kit and VEGF-A/VEGFR-2, contributing to their selective and early proliferation. Our findings describe a dynamic network of signals in response to the acute loss of a single blood cell type, and reveal the important role of three RTKs in orchestrating the selective activation of HSCs and progenitor cells in thrombocytopenia. SOURCE: Tatyana Grinenko (Tatyana.Grinenko@uniklinikum-dresden.de) -  IKL, Carl Gustav Carus Universitätklinikum Dresden

Pluto Bioinformatics

GSE133947: Hematopoietic stem cell response to acute thrombocytopenia requires signaling through distinct receptor tyrosine kinases