BMP signalling differentially regulates distinct haematopoietic stem cell types

Research output: Contribution to journalArticle

Authors

  • Mihaela Crisan
  • Parham Solaimani Kartalaei
  • Chris Vink
  • Tomoko Yamada-Inagawa
  • Karine Bollerot
  • Wilfred Van Ijcken
  • Reinier Van Der Linden
  • Susana M.Chuva De Sousa Lopes
  • Christine Mummery
  • Elaine Dzierzak

Colleges, School and Institutes

External organisations

  • Erasmus University Medical Center
  • EDINBURGH UNIVERSITY
  • Leiden University Medical Center - LUMC

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.

Details

Original languageEnglish
Article number8040
JournalNature Communications
Volume6
Publication statusPublished - 18 Aug 2015