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

Research output: Contribution to journalArticle

26 Scopus citations

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 languageEnglish (US)
Pages (from-to)1418-1426
Number of pages9
JournalBlood
Volume125
Issue number9
DOIs
StatePublished - Jan 1 2015

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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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