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BMP signalling differentially regulates distinct haematopoietic stem cell types.

TitleBMP signalling differentially regulates distinct haematopoietic stem cell types.
Publication TypeJournal Article
Year of Publication2015
AuthorsCrisan M, Kartalaei PSolaimani, Vink CS, Vink C, Yamada-Inagawa T, Bollerot K, van IJcken W, van der Linden R, Lopes SMChuva de, Monteiro R, Mummery C, Dzierzak E
JournalNat Commun
Date Published2015 Aug 18
KeywordsAnimals, Benzofurans, Bone Morphogenetic Proteins, Embryo, Mammalian, Female, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Hematopoietic Stem Cells, Male, Mice, Mice, Transgenic, Nerve Tissue Proteins, Nuclear Proteins, Quinolines, Signal Transduction

Adult haematopoiesis is the outcome of distinct haematopoietic stem cell (HSC) subtypes with self-renewable repopulating ability, but with different haematopoietic cell lineage outputs. The molecular basis for this heterogeneity is largely unknown. BMP signalling regulates HSCs as they are first generated in the aorta-gonad-mesonephros region, but at later developmental stages, its role in HSCs is controversial. Here we show that HSCs in murine fetal liver and the bone marrow are of two types that can be prospectively isolated--BMP activated and non-BMP activated. Clonal transplantation demonstrates that they have distinct haematopoietic lineage outputs. Moreover, the two HSC types differ in intrinsic genetic programs, thus supporting a role for the BMP signalling axis in the regulation of HSC heterogeneity and lineage output. Our findings provide insight into the molecular control mechanisms that define HSC types and have important implications for reprogramming cells to HSC fate and treatments targeting distinct HSC types.

Alternate JournalNat Commun
PubMed ID26282601
PubMed Central IDPMC4557333
Grant ListR037 DK54077 / DK / NIDDK NIH HHS / United States
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