Hematopoiesis circadian control
Following specification in the dorsal aorta, hematopoietic stem and progenitor cells (HSPCs) proliferate in the HSPC niche, known as the caudal hematopoietic tissue (CHT) in zebrafish. Here, the authors 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, they 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. The authors 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. Together, their data uncover a novel mechanism of HSPC homeostasis, in which EC BMAL1, expressed by the niche, controls the amount of bioavailable glutamine for HSPCs by regulating the expression of genes involved in glutamine synthesis.
Full article: https://doi.org/10.1242/dev.204726
WHY IS THIS IMPORTANT?
This research uncovers a new link between the body’s internal clock and blood cell development. Scientists found that BMAL1, a circadian clock protein, regulates the availability of glutamine in the stem cell environment. Glutamine acts as fuel for blood stem cells, so higher levels lead to increased cell growth.
This discovery is important because it identifies a new mechanism that controls blood formation. Since abnormal stem cell growth is a feature of cancers like leukaemia, understanding this pathway could lead to new treatment strategies. It also suggests that targeting metabolic pathways, such as glutamine production, may help control stem cell behaviour in both disease and regenerative medicine.
Citation:
Petzold T, Lutes LK, Batista KNI, Konle A, Baechler B, Jemelin S, Gerhardt H, Golub R, Scheiermann C, Bertrand JY. BMAL1 modulates glutamine supply to control hematopoietic stem and progenitor cell expansion. Development. 2026 Mar 19:dev.204726. doi: 10.1242/dev.204726. Epub ahead of print. PMID: 41853934.
Funding:
Fondation Privée des Hopitaux de Genève, Gabbiani Fund, Swiss National Fund, European Research Council, Deutsche Forschungsgemeinschaft and the Swiss Cancer League.