Transforming growth factor β drives hemogenic endothelium programming and the transition to hematopoietic stem cells

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Transforming growth factor β drives hemogenic endothelium programming and the transition to hematopoietic stem cells. / Monteiro, Rui; Pinheiro, Philip; Joseph, Nicola; Peterkin, Tessa; Koth, Jana; Repapi, Emmanouela; Bonkhofer, Florian; Kirmizitas, Arif; Patient, Roger.

In: Developmental Cell, Vol. 38, No. 4, 22.08.2016, p. 358-370.

Research output: Contribution to journalArticlepeer-review

Harvard

Monteiro, R, Pinheiro, P, Joseph, N, Peterkin, T, Koth, J, Repapi, E, Bonkhofer, F, Kirmizitas, A & Patient, R 2016, 'Transforming growth factor β drives hemogenic endothelium programming and the transition to hematopoietic stem cells', Developmental Cell, vol. 38, no. 4, pp. 358-370. https://doi.org/10.1016/j.devcel.2016.06.024

APA

Monteiro, R., Pinheiro, P., Joseph, N., Peterkin, T., Koth, J., Repapi, E., Bonkhofer, F., Kirmizitas, A., & Patient, R. (2016). Transforming growth factor β drives hemogenic endothelium programming and the transition to hematopoietic stem cells. Developmental Cell, 38(4), 358-370. https://doi.org/10.1016/j.devcel.2016.06.024

Vancouver

Author

Monteiro, Rui ; Pinheiro, Philip ; Joseph, Nicola ; Peterkin, Tessa ; Koth, Jana ; Repapi, Emmanouela ; Bonkhofer, Florian ; Kirmizitas, Arif ; Patient, Roger. / Transforming growth factor β drives hemogenic endothelium programming and the transition to hematopoietic stem cells. In: Developmental Cell. 2016 ; Vol. 38, No. 4. pp. 358-370.

Bibtex

@article{4ab36e1a11fd4f6bbc7bca8a881087eb,
title = "Transforming growth factor β drives hemogenic endothelium programming and the transition to hematopoietic stem cells",
abstract = "Hematopoietic stem cells (HSCs) are self-renewing multipotent stem cells that generate mature blood lineages throughout life. They, together with hematopoietic progenitor cells (collectively known as HSPCs), emerge from hemogenic endothelium in the floor of the embryonic dorsal aorta by an endothelial-to-hematopoietic transition (EHT). Here we demonstrate that transforming growth factor β (TGFβ) is required for HSPC specification and that it regulates the expression of the Notch ligand Jagged1a in endothelial cells prior to EHT, in a striking parallel with the epithelial-to-mesenchymal transition (EMT). The requirement for TGFβ is two fold and sequential: autocrine via Tgfβ1a and Tgfβ1b produced in the endothelial cells themselves, followed by a paracrine input of Tgfβ3 from the notochord, suggesting that the former programs the hemogenic endothelium and the latter drives EHT. Our findings have important implications for the generation of HSPCs from pluripotent cells in vitro.",
keywords = "EHT, hematopoietic stem cell, jag1a, notch, TGFβ, zebrafish",
author = "Rui Monteiro and Philip Pinheiro and Nicola Joseph and Tessa Peterkin and Jana Koth and Emmanouela Repapi and Florian Bonkhofer and Arif Kirmizitas and Roger Patient",
year = "2016",
month = aug,
day = "22",
doi = "10.1016/j.devcel.2016.06.024",
language = "English",
volume = "38",
pages = "358--370",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Elsevier",
number = "4",

}

RIS

TY - JOUR

T1 - Transforming growth factor β drives hemogenic endothelium programming and the transition to hematopoietic stem cells

AU - Monteiro, Rui

AU - Pinheiro, Philip

AU - Joseph, Nicola

AU - Peterkin, Tessa

AU - Koth, Jana

AU - Repapi, Emmanouela

AU - Bonkhofer, Florian

AU - Kirmizitas, Arif

AU - Patient, Roger

PY - 2016/8/22

Y1 - 2016/8/22

N2 - Hematopoietic stem cells (HSCs) are self-renewing multipotent stem cells that generate mature blood lineages throughout life. They, together with hematopoietic progenitor cells (collectively known as HSPCs), emerge from hemogenic endothelium in the floor of the embryonic dorsal aorta by an endothelial-to-hematopoietic transition (EHT). Here we demonstrate that transforming growth factor β (TGFβ) is required for HSPC specification and that it regulates the expression of the Notch ligand Jagged1a in endothelial cells prior to EHT, in a striking parallel with the epithelial-to-mesenchymal transition (EMT). The requirement for TGFβ is two fold and sequential: autocrine via Tgfβ1a and Tgfβ1b produced in the endothelial cells themselves, followed by a paracrine input of Tgfβ3 from the notochord, suggesting that the former programs the hemogenic endothelium and the latter drives EHT. Our findings have important implications for the generation of HSPCs from pluripotent cells in vitro.

AB - Hematopoietic stem cells (HSCs) are self-renewing multipotent stem cells that generate mature blood lineages throughout life. They, together with hematopoietic progenitor cells (collectively known as HSPCs), emerge from hemogenic endothelium in the floor of the embryonic dorsal aorta by an endothelial-to-hematopoietic transition (EHT). Here we demonstrate that transforming growth factor β (TGFβ) is required for HSPC specification and that it regulates the expression of the Notch ligand Jagged1a in endothelial cells prior to EHT, in a striking parallel with the epithelial-to-mesenchymal transition (EMT). The requirement for TGFβ is two fold and sequential: autocrine via Tgfβ1a and Tgfβ1b produced in the endothelial cells themselves, followed by a paracrine input of Tgfβ3 from the notochord, suggesting that the former programs the hemogenic endothelium and the latter drives EHT. Our findings have important implications for the generation of HSPCs from pluripotent cells in vitro.

KW - EHT

KW - hematopoietic stem cell

KW - jag1a

KW - notch

KW - TGFβ

KW - zebrafish

UR - http://www.scopus.com/inward/record.url?scp=84995529488&partnerID=8YFLogxK

U2 - 10.1016/j.devcel.2016.06.024

DO - 10.1016/j.devcel.2016.06.024

M3 - Article

C2 - 27499523

AN - SCOPUS:84995529488

VL - 38

SP - 358

EP - 370

JO - Developmental Cell

JF - Developmental Cell

SN - 1534-5807

IS - 4

ER -