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BMP signalling differentially regulates distinct haematopoietic stem cell types.
- Source :
-
Nature communications [Nat Commun] 2015 Aug 18; Vol. 6, pp. 8040. Date of Electronic Publication: 2015 Aug 18. - Publication Year :
- 2015
-
Abstract
- 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.
- Subjects :
- Animals
Benzofurans
Bone Morphogenetic Proteins genetics
Embryo, Mammalian
Female
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
Male
Mice
Mice, Transgenic
Nerve Tissue Proteins genetics
Nerve Tissue Proteins metabolism
Nuclear Proteins genetics
Nuclear Proteins metabolism
Quinolines
Bone Morphogenetic Proteins metabolism
Gene Expression Regulation, Developmental physiology
Hematopoietic Stem Cells physiology
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 26282601
- Full Text :
- https://doi.org/10.1038/ncomms9040