BMAL1 modulates glutamine supply to control hematopoietic stem and progenitor cell expansion

Here we demonstrate that bmal1a, a core component of the circadian clock machinery, is expressed in CHT endothelial cells (ECs) and affects HSPCs in a non-cell autonomous manner. Using endothelial cell-specific dominant-negative Bmal1a zebrafish lines, we demonstrate a striking increase in HSPC numbers in the CHT, resulting from enhanced HSPC proliferation.

RNA-sequencing of dominant-negative bmal1a ECs sorted from the CHT shows a downregulation of glud1a, resulting in increased glutamine levels in the CHT. This newly discovered bmal1a-glud1a-glutamine pathway fuels HSPC expansion. We demonstrate that this glutamine synthesis pathway controlling HSPC expansion is likely conserved in the mouse fetal liver (FL) niche, in which hepatocytes are the likely source of glutamine.