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BMP signalling differentially regulates distinct haematopoietic stem cell types

Author

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  • Mihaela Crisan

    (Erasmus MC Stem Cell Institute, Erasmus Medical Center, Wytemaweg 80
    University of Edinburgh, Centre for Inflammation Research, Queens Medical Research Institute, 47 Little France Crescent)

  • Parham Solaimani Kartalaei

    (Erasmus MC Stem Cell Institute, Erasmus Medical Center, Wytemaweg 80
    University of Edinburgh, Centre for Inflammation Research, Queens Medical Research Institute, 47 Little France Crescent)

  • Chris S. Vink

    (Erasmus MC Stem Cell Institute, Erasmus Medical Center, Wytemaweg 80
    University of Edinburgh, Centre for Inflammation Research, Queens Medical Research Institute, 47 Little France Crescent)

  • Tomoko Yamada-Inagawa

    (Erasmus MC Stem Cell Institute, Erasmus Medical Center, Wytemaweg 80)

  • Karine Bollerot

    (Erasmus MC Stem Cell Institute, Erasmus Medical Center, Wytemaweg 80)

  • Wilfred van IJcken

    (Center for Biomics, Erasmus Medical Center, Wytemaweg 80)

  • Reinier van der Linden

    (Erasmus MC Stem Cell Institute, Erasmus Medical Center, Wytemaweg 80)

  • Susana M. Chuva de Sousa Lopes

    (Leiden University Medical Center, Building 2, Einthovenweg 20)

  • Rui Monteiro

    (Leiden University Medical Center, Building 2, Einthovenweg 20)

  • Christine Mummery

    (Leiden University Medical Center, Building 2, Einthovenweg 20)

  • Elaine Dzierzak

    (Erasmus MC Stem Cell Institute, Erasmus Medical Center, Wytemaweg 80
    University of Edinburgh, Centre for Inflammation Research, Queens Medical Research Institute, 47 Little France Crescent)

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.

Suggested Citation

  • Mihaela Crisan & Parham Solaimani Kartalaei & Chris S. Vink & Tomoko Yamada-Inagawa & Karine Bollerot & Wilfred van IJcken & Reinier van der Linden & Susana M. Chuva de Sousa Lopes & Rui Monteiro & Ch, 2015. "BMP signalling differentially regulates distinct haematopoietic stem cell types," Nature Communications, Nature, vol. 6(1), pages 1-9, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9040
    DOI: 10.1038/ncomms9040
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    Cited by:

    1. Yumin Liu & Linjuan Shi & Yifan Chen & Sifan Luo & Yuehang Chen & Hongtian Chen & Wenlang Lan & Xun Lu & Zhan Cao & Zehua Ye & Jinping Li & Bo Yu & Elaine Dzierzak & Zhuan Li, 2024. "Autophagy regulates the maturation of hematopoietic precursors in the embryo," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Zaniah N. Gonzalez Galofre & Alastair M. Kilpatrick & Madalena Marques & Diana Sá da Bandeira & Telma Ventura & Mario Gomez Salazar & Léa Bouilleau & Yvan Marc & Ana B. Barbosa & Fiona Rossi & Mariana, 2024. "Runx1+ vascular smooth muscle cells are essential for hematopoietic stem and progenitor cell development in vivo," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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