Notch1 acts via Foxc2 to promote definitive hematopoiesis via effects on hemogenic endothelium

Il Ho Jang; Yi Fen Lu; Long Zhao; Pamela L. Wenzel; Tsutomu Kume; Sumon M. Datta; Natasha Arora; Jordi Guiu; Mounia Lagha; Peter G. Kim; Eun Kyoung Do; Jae Ho Kim; Thorsten M. Schlaeger; Leonard I. Zon; Anna Bigas; Caroline E. Burns; George Q. Daley

doi:10.1182/blood-2014-04-568170

Notch1 acts via Foxc2 to promote definitive hematopoiesis via effects on hemogenic endothelium

Il Ho Jang, Yi Fen Lu, Long Zhao, Pamela L. Wenzel, Tsutomu Kume, Sumon M. Datta, Natasha Arora, Jordi Guiu, Mounia Lagha, Peter G. Kim, Eun Kyoung Do, Jae Ho Kim, Thorsten M. Schlaeger, Leonard I. Zon, Anna Bigas, Caroline E. Burns^*, George Q. Daley

^*Corresponding author for this work

28 Citations (Scopus)

Abstract

Hematopoietic and vascular development share many common features, including cell surface markers and sites of origin. Recent lineage-tracing studies have established that definitive hematopoietic stem and progenitor cells arise from vascular endothelial-cadherin⁺ hemogenic endothelial cells of the aorta-gonad-mesonephros region, but the genetic programs underlying the specification of hemogenic endothelial cells remain poorly defined. Here, we discovered that Notch induction enhances hematopoietic potential and promotes the specification of hemogenic endothelium in differentiating cultures of mouse embryonic stem cells, and we identified Foxc2 as a highly upregulated transcript in the hemogenic endothelial population. Studies in zebrafish and mouse embryos revealed that Foxc2 and its orthologs are required for the proper development of definitive hematopoiesis and function downstream of Notch signaling in the hemogenic endothelium. These data establish a pathway linking Notch signaling to Foxc2 in hemogenic endothelial cells to promote definitive hematopoiesis.

Original language	English
Journal	Blood
Volume	125
Issue number	9
Pages (from-to)	1418-1426
Number of pages	9
ISSN	0006-4971
DOIs	https://doi.org/10.1182/blood-2014-04-568170
Publication status	Published - 1 Jan 2015
Externally published	Yes

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Jang, I. H., Lu, Y. F., Zhao, L., Wenzel, P. L., Kume, T., Datta, S. M., Arora, N., Guiu, J., Lagha, M., Kim, P. G., Do, E. K., Kim, J. H., Schlaeger, T. M., Zon, L. I., Bigas, A., Burns, C. E., & Daley, G. Q. (2015). Notch1 acts via Foxc2 to promote definitive hematopoiesis via effects on hemogenic endothelium. Blood, 125(9), 1418-1426. https://doi.org/10.1182/blood-2014-04-568170

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title = "Notch1 acts via Foxc2 to promote definitive hematopoiesis via effects on hemogenic endothelium",

abstract = "Hematopoietic and vascular development share many common features, including cell surface markers and sites of origin. Recent lineage-tracing studies have established that definitive hematopoietic stem and progenitor cells arise from vascular endothelial-cadherin+ hemogenic endothelial cells of the aorta-gonad-mesonephros region, but the genetic programs underlying the specification of hemogenic endothelial cells remain poorly defined. Here, we discovered that Notch induction enhances hematopoietic potential and promotes the specification of hemogenic endothelium in differentiating cultures of mouse embryonic stem cells, and we identified Foxc2 as a highly upregulated transcript in the hemogenic endothelial population. Studies in zebrafish and mouse embryos revealed that Foxc2 and its orthologs are required for the proper development of definitive hematopoiesis and function downstream of Notch signaling in the hemogenic endothelium. These data establish a pathway linking Notch signaling to Foxc2 in hemogenic endothelial cells to promote definitive hematopoiesis.",

author = "Jang, {Il Ho} and Lu, {Yi Fen} and Long Zhao and Wenzel, {Pamela L.} and Tsutomu Kume and Datta, {Sumon M.} and Natasha Arora and Jordi Guiu and Mounia Lagha and Kim, {Peter G.} and Do, {Eun Kyoung} and Kim, {Jae Ho} and Schlaeger, {Thorsten M.} and Zon, {Leonard I.} and Anna Bigas and Burns, {Caroline E.} and Daley, {George Q.}",

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doi = "10.1182/blood-2014-04-568170",

language = "English",

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T1 - Notch1 acts via Foxc2 to promote definitive hematopoiesis via effects on hemogenic endothelium

AU - Jang, Il Ho

AU - Lu, Yi Fen

AU - Zhao, Long

AU - Wenzel, Pamela L.

AU - Kume, Tsutomu

AU - Datta, Sumon M.

AU - Arora, Natasha

AU - Guiu, Jordi

AU - Lagha, Mounia

AU - Kim, Peter G.

AU - Do, Eun Kyoung

AU - Kim, Jae Ho

AU - Schlaeger, Thorsten M.

AU - Zon, Leonard I.

AU - Bigas, Anna

AU - Burns, Caroline E.

AU - Daley, George Q.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Hematopoietic and vascular development share many common features, including cell surface markers and sites of origin. Recent lineage-tracing studies have established that definitive hematopoietic stem and progenitor cells arise from vascular endothelial-cadherin+ hemogenic endothelial cells of the aorta-gonad-mesonephros region, but the genetic programs underlying the specification of hemogenic endothelial cells remain poorly defined. Here, we discovered that Notch induction enhances hematopoietic potential and promotes the specification of hemogenic endothelium in differentiating cultures of mouse embryonic stem cells, and we identified Foxc2 as a highly upregulated transcript in the hemogenic endothelial population. Studies in zebrafish and mouse embryos revealed that Foxc2 and its orthologs are required for the proper development of definitive hematopoiesis and function downstream of Notch signaling in the hemogenic endothelium. These data establish a pathway linking Notch signaling to Foxc2 in hemogenic endothelial cells to promote definitive hematopoiesis.

AB - Hematopoietic and vascular development share many common features, including cell surface markers and sites of origin. Recent lineage-tracing studies have established that definitive hematopoietic stem and progenitor cells arise from vascular endothelial-cadherin+ hemogenic endothelial cells of the aorta-gonad-mesonephros region, but the genetic programs underlying the specification of hemogenic endothelial cells remain poorly defined. Here, we discovered that Notch induction enhances hematopoietic potential and promotes the specification of hemogenic endothelium in differentiating cultures of mouse embryonic stem cells, and we identified Foxc2 as a highly upregulated transcript in the hemogenic endothelial population. Studies in zebrafish and mouse embryos revealed that Foxc2 and its orthologs are required for the proper development of definitive hematopoiesis and function downstream of Notch signaling in the hemogenic endothelium. These data establish a pathway linking Notch signaling to Foxc2 in hemogenic endothelial cells to promote definitive hematopoiesis.

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JO - Blood

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Notch1 acts via Foxc2 to promote definitive hematopoiesis via effects on hemogenic endothelium

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