Format

Send to

Choose Destination
See comment in PubMed Commons below
Nat Commun. 2015 Aug 18;6:8040. doi: 10.1038/ncomms9040.

BMP signalling differentially regulates distinct haematopoietic stem cell types.

Author information

1
1] Department of Cell Biology, Erasmus MC Stem Cell Institute, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands [2] University of Edinburgh, Centre for Inflammation Research, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
2
Department of Cell Biology, Erasmus MC Stem Cell Institute, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
3
Center for Biomics, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, Netherlands.
4
Department of Anatomy and Embryology, Leiden University Medical Center, Building 2, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.

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.

PMID:
26282601
PMCID:
PMC4557333
DOI:
10.1038/ncomms9040
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center