BMP and Hedgehog regulate distinct AGM hematopoietic stem cells ex vivo

Mihaela Crisan; Parham Solaimani Kartalaei; Alex Neagu; Sofia Karkanpouna; Tomoko Yamada-Inagawa; Caterina Purini; Chris Vink; Reiner van der Linden; Wilfred Van Ijcken; Susana  Chuva de Sousa Lopes; Rui Monteiro; Christine L. Mummery; Elaine Dzierzak

doi:10.1016/j.stemcr.2016.01.016

BMP and Hedgehog regulate distinct AGM hematopoietic stem cells ex vivo

Mihaela Crisan, Parham Solaimani Kartalaei, Alex Neagu, Sofia Karkanpouna, Tomoko Yamada-Inagawa, Caterina Purini, Chris Vink, Reiner van der Linden, Wilfred Van Ijcken, Susana Chuva de Sousa Lopes, Rui Monteiro, Christine L. 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 HSCs are produced in the aorta-gonad-mesonephros (AGM) region of the embryo through endothelial to a hematopoietic transition. 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 is BMP-activated and the other is a non-BMP-activated HSC type that is indirectly controlled by Hedgehog signalling through the VEGF pathway. Transcriptomic analyses demonstrate that the two HSC types express distinct but overlapping genetic programs. These results revealing the bifurcation in HSC types at early embryonic stages in the AGM explant model suggest that their development is dependent upon the signalling molecules in the microenvironment.

Original language	English
Journal	Stem Cell Reports
DOIs	https://doi.org/10.1016/j.stemcr.2016.01.016
Publication status	Published - 25 Feb 2016

Keywords / Materials (for Non-textual outputs)

hematopoietic stem/progenitor cells
HPSCs
AGM
BMP
Hh
VEGF
development
Hematopoiesis

Access to Document

10.1016/j.stemcr.2016.01.016Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

1-s2.0-S2213671116000333-main
Under a Creative Commons license
Final published version, 2.47 MBLicence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

Characterisation of the first HSC's During Mouse Ontogeny
Dzierzak, E.
Non-EU other
1/10/13 → 31/03/16
Project: Research

Mihaela Crisan
- mihaela.crisaned.acuk
- Deanery of Clinical Sciences - Senior Research Fellow
- Centre for Cardiovascular Science
Person: Academic: Research Active
Elaine Dzierzak
- Elaine.Dzierzaked.acuk
- Deanery of Clinical Sciences - Chair of Haematological Regeneration
- Centre for Inflammation Research
- Edinburgh Haematopoiesis Network
Person: Academic: Research Active

Cite this

@article{1d95f953240243578e1b47f4d3d42315,

title = "BMP and Hedgehog regulate distinct AGM hematopoietic stem cells ex vivo",

abstract = "Hematopoietic stem cells (HSC), the self-renewing cells of the adult blooddifferentiation hierarchy are generated during embryonic stages. The first HSCs are produced in the aorta-gonad-mesonephros (AGM) region of the embryo through endothelial to a hematopoietic transition. 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 is BMP-activated and the other is a non-BMP-activated HSC type that is indirectly controlled by Hedgehog signalling through the VEGF pathway. Transcriptomic analyses demonstrate that the two HSC types express distinct but overlapping genetic programs. These results revealing the bifurcation in HSC types at early embryonic stages in the AGM explant model suggest that their development is dependent upon the signalling molecules in the microenvironment.",

keywords = "hematopoietic stem/progenitor cells, HPSCs, AGM, BMP, Hh, VEGF, development, Hematopoiesis",

author = "Mihaela Crisan and {Solaimani Kartalaei}, Parham and Alex Neagu and Sofia Karkanpouna and Tomoko Yamada-Inagawa and Caterina Purini and Chris Vink and {van der Linden}, Reiner and {Van Ijcken}, Wilfred and {Chuva de Sousa Lopes}, Susana and Rui Monteiro and Mummery, {Christine L.} and Elaine Dzierzak",

year = "2016",

month = feb,

day = "25",

doi = "10.1016/j.stemcr.2016.01.016",

language = "English",

journal = "Stem Cell Reports",

issn = "2213-6711",

publisher = "Cell Press",

}

TY - JOUR

T1 - BMP and Hedgehog regulate distinct AGM hematopoietic stem cells ex vivo

AU - Crisan, Mihaela

AU - Solaimani Kartalaei, Parham

AU - Neagu, Alex

AU - Karkanpouna, Sofia

AU - Yamada-Inagawa, Tomoko

AU - Purini, Caterina

AU - Vink, Chris

AU - van der Linden, Reiner

AU - Van Ijcken, Wilfred

AU - Chuva de Sousa Lopes, Susana

AU - Monteiro, Rui

AU - Mummery, Christine L.

AU - Dzierzak, Elaine

PY - 2016/2/25

Y1 - 2016/2/25

N2 - Hematopoietic stem cells (HSC), the self-renewing cells of the adult blooddifferentiation hierarchy are generated during embryonic stages. The first HSCs are produced in the aorta-gonad-mesonephros (AGM) region of the embryo through endothelial to a hematopoietic transition. 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 is BMP-activated and the other is a non-BMP-activated HSC type that is indirectly controlled by Hedgehog signalling through the VEGF pathway. Transcriptomic analyses demonstrate that the two HSC types express distinct but overlapping genetic programs. These results revealing the bifurcation in HSC types at early embryonic stages in the AGM explant model suggest that their development is dependent upon the signalling molecules in the microenvironment.

AB - Hematopoietic stem cells (HSC), the self-renewing cells of the adult blooddifferentiation hierarchy are generated during embryonic stages. The first HSCs are produced in the aorta-gonad-mesonephros (AGM) region of the embryo through endothelial to a hematopoietic transition. 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 is BMP-activated and the other is a non-BMP-activated HSC type that is indirectly controlled by Hedgehog signalling through the VEGF pathway. Transcriptomic analyses demonstrate that the two HSC types express distinct but overlapping genetic programs. These results revealing the bifurcation in HSC types at early embryonic stages in the AGM explant model suggest that their development is dependent upon the signalling molecules in the microenvironment.

KW - hematopoietic stem/progenitor cells

KW - HPSCs

KW - AGM

KW - BMP

KW - Hh

KW - VEGF

KW - development

KW - Hematopoiesis

U2 - 10.1016/j.stemcr.2016.01.016

DO - 10.1016/j.stemcr.2016.01.016

M3 - Article

SN - 2213-6711

JO - Stem Cell Reports

JF - Stem Cell Reports

ER -

BMP and Hedgehog regulate distinct AGM hematopoietic stem cells ex vivo

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

Access to Document

Fingerprint

Projects

Characterisation of the first HSC's During Mouse Ontogeny

Profiles

Mihaela Crisan

Elaine Dzierzak

Cite this