BMP signalling differentially regulates distinct haematopoietic stem cell types

Nat Commun. 2015 Aug 18;6:8040. doi: 10.1038/ncomms9040.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzofurans
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism*
  • Embryo, Mammalian
  • Female
  • Gene Expression Regulation, Developmental / physiology*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hematopoietic Stem Cells / physiology*
  • Male
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Quinolines
  • Signal Transduction / physiology*

Substances

  • (3aS,4S,9bS)-N-(2-(8-cyano-1-formyl-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo(3,2-c)quinolin-4-yl)-2-methylpropyl)-4,6-difluorobenzofuran-2-carboxyamide
  • Babam2 protein, mouse
  • Benzofurans
  • Bone Morphogenetic Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Quinolines
  • Green Fluorescent Proteins

Associated data

  • GEO/GSE70132