Pivotal role of Pten in the balance between proliferation and differentiation of hematopoietic stem cells in zebrafish
- Authors
- Choorapoikayil, S., Kers, R., Herbomel, P., Kissa, K., and den Hertog, J.
- ID
- ZDB-PUB-131115-12
- Date
- 2014
- Source
- Blood : (Unknown)
- Registered Authors
- Choorapoikayil, Suma, den Hertog, Jeroen, Herbomel, Philippe, Kissa-Marin, Karima
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cell Differentiation/drug effects
- Cell Differentiation/genetics*
- Cell Lineage/genetics
- Cell Proliferation/drug effects
- Chromones/pharmacology
- Gene Knockout Techniques
- Hematopoiesis/genetics
- Hematopoietic Stem Cells/cytology*
- Hematopoietic Stem Cells/drug effects
- Hematopoietic Stem Cells/metabolism*
- Morpholines/pharmacology
- Mutation
- Neutrophils/cytology
- Neutrophils/metabolism
- PTEN Phosphohydrolase/genetics*
- PTEN Phosphohydrolase/metabolism*
- Phosphatidylinositol 3-Kinases/antagonists & inhibitors
- Signal Transduction/drug effects
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 24124088 Full text @ Blood
Self-renewing hematopoietic stem/progenitor cells (HSPCs) produce blood cells of all lineages throughout life. PTEN, a tumor suppressor that antagonizes PI3-Kinase (PI3K) signaling, is frequently mutated in hematologic malignancies such as bone marrow failure and leukemia. We set out to investigate if Pten is required for hematopoiesis. Analysis of zebrafish mutants lacking functional Pten revealed that HSPCs colonized the caudal hematopoietic tissue (CHT) 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.