PUBLICATION
Notch1 acts via Foxc2 to promote definitive hematopoiesis via effects on hemogenic endothelium
- Authors
- 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.
- ID
- ZDB-PUB-150115-2
- Date
- 2015
- Source
- Blood 125(9): 1418-26 (Journal)
- Registered Authors
- Burns (Erter), Caroline, Datta, Sumon, Schlaeger, Thorsten, Zhao, Long, Zon, Leonard I.
- Keywords
- none
- MeSH Terms
-
- Animals
- Apoptosis
- Blotting, Western
- Cell Differentiation
- Cell Lineage
- Cell Proliferation
- Cells, Cultured
- Embryonic Stem Cells/cytology*
- Embryonic Stem Cells/metabolism
- Endothelium, Vascular/cytology*
- Endothelium, Vascular/metabolism
- Forkhead Transcription Factors/genetics
- Forkhead Transcription Factors/metabolism*
- Gene Expression Regulation, Developmental*
- Hematopoiesis/physiology*
- Hematopoietic Stem Cells/cytology*
- Hematopoietic Stem Cells/metabolism
- Mice
- RNA, Messenger/genetics
- Real-Time Polymerase Chain Reaction
- Receptor, Notch1/genetics
- Receptor, Notch1/metabolism*
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 25587036 Full text @ Blood
Citation
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):1418-26.
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 VE-cadherin(+) hemogenic endothelial cells of the aorta-gonad-mesonephros (AGM) 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 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping