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

TY - JOUR

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.

UR - http://www.scopus.com/inward/record.url?scp=84961551935&partnerID=8YFLogxK

U2 - 10.1182/blood-2014-04-568170

DO - 10.1182/blood-2014-04-568170

M3 - Journal article

C2 - 25587036

AN - SCOPUS:84961551935

SN - 0006-4971

VL - 125

SP - 1418

EP - 1426

JO - Blood

JF - Blood

IS - 9

ER -