BMP signalling differentially regulates distinct haematopoietic stem cell types

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, Christine Mummery and Elaine Dzierzak ()
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Mihaela Crisan: Erasmus MC Stem Cell Institute, Erasmus Medical Center, Wytemaweg 80
Parham Solaimani Kartalaei: Erasmus MC Stem Cell Institute, Erasmus Medical Center, Wytemaweg 80
Chris S. Vink: Erasmus MC Stem Cell Institute, Erasmus Medical Center, Wytemaweg 80
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

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9040

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