PUBLICATION
Transforming Growth Factor ? Drives Hemogenic Endothelium Programming and the Transition to Hematopoietic Stem Cells
- Authors
- Monteiro, R., Pinheiro, P., Joseph, N., Peterkin, T., Koth, J., Repapi, E., Bonkhofer, F., Kirmizitas, A., Patient, R.
- ID
- ZDB-PUB-160809-6
- Date
- 2016
- Source
- Developmental Cell 38(4): 358-70 (Journal)
- Registered Authors
- Koth, Jana, Monteiro, Rui, Patient, Roger K., Peterkin, Tessa, Pinheiro, Philip
- Keywords
- EHT, TGF?, hematopoietic stem cell, jag1a, notch, zebrafish
- MeSH Terms
-
- Transforming Growth Factor beta2/genetics
- Transforming Growth Factor beta2/metabolism*
- Hematopoietic Stem Cells/cytology*
- Animals, Genetically Modified
- Core Binding Factor Alpha 2 Subunit/genetics
- Transforming Growth Factor beta1/genetics
- Transforming Growth Factor beta1/metabolism*
- Jagged-1 Protein/biosynthesis
- Jagged-1 Protein/genetics
- Cell Differentiation
- Endothelium, Vascular/embryology*
- Multipotent Stem Cells/cytology
- Morpholinos/genetics
- Notochord/embryology
- Epithelial-Mesenchymal Transition
- Animals
- Signal Transduction
- Zebrafish/embryology*
- Zebrafish Proteins/biosynthesis
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Vascular Endothelial Growth Factor A/metabolism
- Transforming Growth Factor beta3/genetics
- Transforming Growth Factor beta3/metabolism*
- PubMed
- 27499523 Full text @ Dev. Cell
Citation
Monteiro, R., Pinheiro, P., Joseph, N., Peterkin, T., Koth, J., Repapi, E., Bonkhofer, F., Kirmizitas, A., Patient, R. (2016) Transforming Growth Factor ? Drives Hemogenic Endothelium Programming and the Transition to Hematopoietic Stem Cells. Developmental Cell. 38(4):358-70.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping