Haematopoietic stem and progenitor cell heterogeneity is inherited from the embryonic endothelium.

Autor: Ghersi JJ; Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT, USA.; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.; Vascular Biology & Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA., Baldissera G; Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT, USA.; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.; Vascular Biology & Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA., Hintzen J; Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT, USA.; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.; Vascular Biology & Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA., Luff SA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Center for Advancement of Blood Cancer Therapies, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Cheng S; Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT, USA.; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.; Vascular Biology & Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA., Xia IF; Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT, USA.; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.; Vascular Biology & Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA., Sturgeon CM; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Center for Advancement of Blood Cancer Therapies, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Nicoli S; Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale University School of Medicine, New Haven, CT, USA. stefania.nicoli@yale.edu.; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA. stefania.nicoli@yale.edu.; Vascular Biology & Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA. stefania.nicoli@yale.edu.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2023 Aug; Vol. 25 (8), pp. 1135-1145. Date of Electronic Publication: 2023 Jul 17.
DOI: 10.1038/s41556-023-01187-9
Abstrakt: Definitive haematopoietic stem and progenitor cells (HSPCs) generate erythroid, lymphoid and myeloid lineages. HSPCs are produced in the embryo via transdifferentiation of haemogenic endothelial cells in the aorta-gonad-mesonephros (AGM). HSPCs in the AGM are heterogeneous in differentiation and proliferative output, but how these intrinsic differences are acquired remains unanswered. Here we discovered that loss of microRNA (miR)-128 in zebrafish leads to an expansion of HSPCs in the AGM with different cell cycle states and a skew towards erythroid and lymphoid progenitors. Manipulating miR-128 in differentiating haemogenic endothelial cells, before their transition to HSPCs, recapitulated the lineage skewing in both zebrafish and human pluripotent stem cells. miR-128 promotes Wnt and Notch signalling in the AGM via post-transcriptional repression of the Wnt inhibitor csnk1a1 and the Notch ligand jag1b. De-repression of cskn1a1 resulted in replicative and erythroid-biased HSPCs, whereas de-repression of jag1b resulted in G2/M and lymphoid-biased HSPCs with long-term consequence on the respective blood lineages. We propose that HSPC heterogeneity arises in the AGM endothelium and is programmed in part by Wnt and Notch signalling.
(© 2023. The Author(s).)
Databáze: MEDLINE
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