Back to Search
Start Over
Pivotal role of Pten in the balance between proliferation and differentiation of hematopoietic stem cells in zebrafish.
- Source :
-
Blood [Blood] 2014 Jan 09; Vol. 123 (2), pp. 184-90. Date of Electronic Publication: 2013 Oct 11. - Publication Year :
- 2014
-
Abstract
- Self-renewing hematopoietic stem/progenitor cells (HSPCs) produce blood cells of all lineages throughout life. Phosphatase and tensin homolog (PTEN), a tumor suppressor that antagonizes phosphatidylinositol 3-kinase (PI3K) signaling, is frequently mutated in hematologic malignancies such as bone marrow failure and leukemia. We set out to investigate whether Pten is required for hematopoiesis. Analysis of zebrafish mutants lacking functional Pten revealed that HSPCs colonized the caudal hematopoietic tissue normally. There, HSPCs hyperproliferated and engaged in all blood lineages. However, they failed to differentiate into mature blood cells. Hence, Pten mutant zebrafish embryos displayed hallmarks of leukemia in humans. Inhibition of PI3K signaling in mutants lacking functional Pten suppressed hyperproliferation and released the differentiation arrest. We conclude that Pten has an essential role in the balance between proliferation and differentiation of blood cells.
- Subjects :
- Animals
Animals, Genetically Modified
Cell Differentiation drug effects
Cell Lineage genetics
Cell Proliferation drug effects
Chromones pharmacology
Gene Knockout Techniques
Hematopoiesis genetics
Hematopoietic Stem Cells drug effects
Morpholines pharmacology
Mutation
Neutrophils cytology
Neutrophils metabolism
Phosphoinositide-3 Kinase Inhibitors
Signal Transduction drug effects
Zebrafish embryology
Zebrafish genetics
Zebrafish metabolism
Cell Differentiation genetics
Hematopoietic Stem Cells cytology
Hematopoietic Stem Cells metabolism
PTEN Phosphohydrolase genetics
PTEN Phosphohydrolase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 123
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 24124088
- Full Text :
- https://doi.org/10.1182/blood-2013-05-501544