PUBLICATION
A somitic Wnt16/Notch pathway specifies haematopoietic stem cells
- Authors
- Clements, W.K., Kim, A.D., Ong, K.G., Moore, J.C., Lawson, N.D., and Traver, D.
- ID
- ZDB-PUB-110613-31
- Date
- 2011
- Source
- Nature 474(7350): 220-224 (Journal)
- Registered Authors
- Clements, Wilson, Lawson, Nathan, Moore, John, Traver, David
- Keywords
- developmental biology, stem cells
- MeSH Terms
-
- Membrane Proteins/metabolism
- Signal Transduction*
- Somites/cytology
- Somites/metabolism*
- Receptors, Notch/metabolism*
- Intracellular Signaling Peptides and Proteins
- Cell Differentiation*
- Nerve Tissue Proteins/metabolism
- Wnt Proteins/deficiency
- Wnt Proteins/genetics
- Wnt Proteins/metabolism*
- Ligands
- Animals
- Zebrafish Proteins/deficiency
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Cell Lineage
- Hematopoiesis
- Phenotype
- Zebrafish/metabolism*
- Hematopoietic Stem Cells/cytology*
- Hematopoietic Stem Cells/metabolism*
- PubMed
- 21654806 Full text @ Nature
Citation
Clements, W.K., Kim, A.D., Ong, K.G., Moore, J.C., Lawson, N.D., and Traver, D. (2011) A somitic Wnt16/Notch pathway specifies haematopoietic stem cells. Nature. 474(7350):220-224.
Abstract
Haematopoietic stem cells (HSCs) are a self-renewing population of cells that continuously replenish all blood and immune cells during the lifetime of an individual. HSCs are used clinically to treat a wide array of diseases, including acute leukaemias and congenital blood disorders, but obtaining suitable numbers of cells and finding immune-compatible donors remain serious problems. These difficulties have led to an interest in the conversion of embryonic stem cells or induced pluripotent stem cells into HSCs, which is not possible using current methodologies. To accomplish this goal, it is critical to understand the native mechanisms involved in the specification of HSCs during embryonic development. Here we demonstrate in zebrafish that Wnt16 controls a novel genetic regulatory network required for HSC specification. Non-canonical signalling by Wnt16 is required for somitic expression of the Notch ligands deltaC (dlc) and deltaD (dld), and these ligands are, in turn, required for the establishment of definitive haematopoiesis. Notch signalling downstream of Dlc and Dld is earlier than, and distinct from, known cell-autonomous requirements for Notch, strongly suggesting that novel Notch-dependent relay signal(s) induce the first HSCs in parallel to other established pathways. Our results demonstrate that somite-specific gene expression is required for the production of haemogenic endothelium.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping