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 S. Vink; Reinier Van Der Linden; Wilfred Van Ijcken; Susana M. Chuva De Sousa Lopes; Rui Monteiro; Christine 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 S. Vink, Reinier Van Der Linden, Wilfred Van Ijcken, Susana M. Chuva De Sousa Lopes, Rui Monteiro, Christine Mummery, Elaine Dzierzak^*

^*Corresponding author for this work

Cancer and Genomic Sciences

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

19 Citations (Scopus)

Abstract

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 and 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/Smad-activated 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 signaling 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 signaling molecules in the microenvironment.

Original language	English
Pages (from-to)	383-395
Number of pages	13
Journal	Stem Cell Reports
Volume	6
Issue number	3
DOIs	https://doi.org/10.1016/j.stemcr.2016.01.016
Publication status	Published - 8 Mar 2016

Keywords

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

ASJC Scopus subject areas

Biochemistry
Genetics
Developmental Biology
Cell Biology

Access to Document

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

Cite this

Crisan, M., Solaimani Kartalaei, P., Neagu, A., Karkanpouna, S., Yamada-Inagawa, T., Purini, C., Vink, C. S., Van Der Linden, R., Van Ijcken, W., Chuva De Sousa Lopes, S. M., Monteiro, R., Mummery, C., & Dzierzak, E. (2016). BMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo. Stem Cell Reports, 6(3), 383-395. https://doi.org/10.1016/j.stemcr.2016.01.016

@article{d8ffc6eab1024cf38e955d73b01119e2,

title = "BMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo",

abstract = "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 and 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/Smad-activated 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 signaling 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 signaling molecules in the microenvironment.",

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

author = "Mihaela Crisan and {Solaimani Kartalaei}, Parham and Alex Neagu and Sofia Karkanpouna and Tomoko Yamada-Inagawa and Caterina Purini and Vink, {Chris S.} and {Van Der Linden}, Reinier and {Van Ijcken}, Wilfred and {Chuva De Sousa Lopes}, {Susana M.} and Rui Monteiro and Christine Mummery and Elaine Dzierzak",

year = "2016",

month = mar,

day = "8",

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

language = "English",

volume = "6",

pages = "383--395",

journal = "Stem Cell Reports",

issn = "2213-6711",

publisher = "Elsevier",

number = "3",

}

Crisan, M, Solaimani Kartalaei, P, Neagu, A, Karkanpouna, S, Yamada-Inagawa, T, Purini, C, Vink, CS, Van Der Linden, R, Van Ijcken, W, Chuva De Sousa Lopes, SM, Monteiro, R, Mummery, C & Dzierzak, E 2016, 'BMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo', Stem Cell Reports, vol. 6, no. 3, pp. 383-395. https://doi.org/10.1016/j.stemcr.2016.01.016

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 S.

AU - Van Der Linden, Reinier

AU - Van Ijcken, Wilfred

AU - Chuva De Sousa Lopes, Susana M.

AU - Monteiro, Rui

AU - Mummery, Christine

AU - Dzierzak, Elaine

PY - 2016/3/8

Y1 - 2016/3/8

N2 - 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 and 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/Smad-activated 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 signaling 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 signaling molecules in the microenvironment.

AB - 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 and 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/Smad-activated 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 signaling 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 signaling molecules in the microenvironment.

KW - AGM

KW - BMP

KW - development

KW - hematopoiesis

KW - hematopoietic stem/progenitor cells

KW - Hh

KW - HPSCs

KW - VEGF

UR - http://www.scopus.com/inward/record.url?scp=84960803409&partnerID=8YFLogxK

U2 - 10.1016/j.stemcr.2016.01.016

DO - 10.1016/j.stemcr.2016.01.016

M3 - Article

C2 - 26923823

AN - SCOPUS:84960803409

SN - 2213-6711

VL - 6

SP - 383

EP - 395

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 3

ER -

BMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Fingerprint

Cite this