BMP signalling differentially regulates distinct hematopoietic 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; Elaine Dzierzak

doi:10.1038/ncomms9040

BMP signalling differentially regulates distinct hematopoietic 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, Elaine Dzierzak

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

Hematopoietic stem cells (HSC), the self-renewing cells of the adult blood differentiation hierarchy are generated during embryonic stages. The first adult-repopulating HSCs are produced in the aorta-gonad-mesonephros (AGM) region of the embryo through the transition of a specialized set of endothelial cells to hematopoietic fate. The developmental regulators BMP4 and Hedgehog affect their production/expansion, but it is unknown whether they act to affect the same HSCs. In this study using the BRE GFP reporter mouse strain that identifies BMP/Smadactivated cells, we find that the AGM harbors two types of adult-repopulating HSCs upon explant culture: One type of HSC is BMP-activated. The other is a non-BMP-activated HSC type that is indirectly controlled by Hedgehog signalling through the VEGF pathway. Our results, obtained under defined conditions in which the responsiveness to distinct developmental signalling pathways discriminates two HSC types, are the first to demonstrate that HSC heterogeneity begins already early during development and suggest that the basis of HSC heterogeneity is microenvironment dependent.

Original language	English
Article number	8040
Number of pages	8
Journal	Nature Communications
Volume	6
Early online date	18 Aug 2015
DOIs	https://doi.org/10.1038/ncomms9040
Publication status	Published - 18 Aug 2015

Keywords / Materials (for Non-textual outputs)

HEMATOPOIETIC STEM
PROGENITOR CELLS
HPSCs
AGM
BMP
Hh
VEGF
development
Hematopoiesis

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Elaine Dzierzak
- Elaine.Dzierzaked.acuk
- Deanery of Clinical Sciences - Chair of Haematological Regeneration
- Centre for Inflammation Research
- Edinburgh Haematopoiesis Network
Person: Academic: Research Active

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@article{b2fb4b0f6a904add84725fbe074cfd77,

title = "BMP signalling differentially regulates distinct hematopoietic stem cell types",

abstract = "Hematopoietic stem cells (HSC), the self-renewing cells of the adult blood differentiation hierarchy are generated during embryonic stages. The first adult-repopulating HSCs are produced in the aorta-gonad-mesonephros (AGM) region of the embryo through the transition of a specialized set of endothelial cells to hematopoietic fate. The developmental regulators BMP4 and Hedgehog affect their production/expansion, but it is unknown whether they act to affect the same HSCs. In this study using the BRE GFP reporter mouse strain that identifies BMP/Smadactivated cells, we find that the AGM harbors two types of adult-repopulating HSCs upon explant culture: One type of HSC is BMP-activated. The other is a non-BMP-activated HSC type that is indirectly controlled by Hedgehog signalling through the VEGF pathway. Our results, obtained under defined conditions in which the responsiveness to distinct developmental signalling pathways discriminates two HSC types, are the first to demonstrate that HSC heterogeneity begins already early during development and suggest that the basis of HSC heterogeneity is microenvironment dependent.",

keywords = "HEMATOPOIETIC STEM, PROGENITOR CELLS, HPSCs, AGM, BMP, Hh, VEGF , development, Hematopoiesis",

author = "Mihaela Crisan and {Solaimani Kartalaei}, Parham and Vink, {Chris S.} and Tomoko Yamada-Inagawa and Karine Bollerot and {van IJcken}, Wilfred and {van der Linden}, Reinier and {Chuva de Sousa Lopes}, {Susana M.} and Rui Monteiro and Christine Mummery and Elaine Dzierzak",

note = "Date of Acceptance: 10/07/2015",

year = "2015",

month = aug,

day = "18",

doi = "10.1038/ncomms9040",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

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TY - JOUR

T1 - BMP signalling differentially regulates distinct hematopoietic stem cell types

AU - Crisan, Mihaela

AU - Solaimani Kartalaei, Parham

AU - Vink, Chris S.

AU - Yamada-Inagawa, Tomoko

AU - Bollerot, Karine

AU - van IJcken, Wilfred

AU - van der Linden, Reinier

AU - Chuva de Sousa Lopes, Susana M.

AU - Monteiro, Rui

AU - Mummery, Christine

AU - Dzierzak, Elaine

N1 - Date of Acceptance: 10/07/2015

PY - 2015/8/18

Y1 - 2015/8/18

N2 - Hematopoietic stem cells (HSC), the self-renewing cells of the adult blood differentiation hierarchy are generated during embryonic stages. The first adult-repopulating HSCs are produced in the aorta-gonad-mesonephros (AGM) region of the embryo through the transition of a specialized set of endothelial cells to hematopoietic fate. The developmental regulators BMP4 and Hedgehog affect their production/expansion, but it is unknown whether they act to affect the same HSCs. In this study using the BRE GFP reporter mouse strain that identifies BMP/Smadactivated cells, we find that the AGM harbors two types of adult-repopulating HSCs upon explant culture: One type of HSC is BMP-activated. The other is a non-BMP-activated HSC type that is indirectly controlled by Hedgehog signalling through the VEGF pathway. Our results, obtained under defined conditions in which the responsiveness to distinct developmental signalling pathways discriminates two HSC types, are the first to demonstrate that HSC heterogeneity begins already early during development and suggest that the basis of HSC heterogeneity is microenvironment dependent.

AB - Hematopoietic stem cells (HSC), the self-renewing cells of the adult blood differentiation hierarchy are generated during embryonic stages. The first adult-repopulating HSCs are produced in the aorta-gonad-mesonephros (AGM) region of the embryo through the transition of a specialized set of endothelial cells to hematopoietic fate. The developmental regulators BMP4 and Hedgehog affect their production/expansion, but it is unknown whether they act to affect the same HSCs. In this study using the BRE GFP reporter mouse strain that identifies BMP/Smadactivated cells, we find that the AGM harbors two types of adult-repopulating HSCs upon explant culture: One type of HSC is BMP-activated. The other is a non-BMP-activated HSC type that is indirectly controlled by Hedgehog signalling through the VEGF pathway. Our results, obtained under defined conditions in which the responsiveness to distinct developmental signalling pathways discriminates two HSC types, are the first to demonstrate that HSC heterogeneity begins already early during development and suggest that the basis of HSC heterogeneity is microenvironment dependent.

KW - HEMATOPOIETIC STEM

KW - PROGENITOR CELLS

KW - HPSCs

KW - AGM

KW - BMP

KW - Hh

KW - VEGF

KW - development

KW - Hematopoiesis

U2 - 10.1038/ncomms9040

DO - 10.1038/ncomms9040

M3 - Article

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 8040

ER -

BMP signalling differentially regulates distinct hematopoietic stem cell types

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Elaine Dzierzak

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