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Simultaneous deletion of p21Cip1/Waf1 and caspase-3 accelerates proliferation and partially rescues the differentiation defects of caspase-3 deficient hematopoietic stem cells
- Source :
- PLoS ONE, Vol 9, Iss 10, p e109266 (2014), PLoS ONE
- Publication Year :
- 2014
- Publisher :
- Public Library of Science (PLoS), 2014.
-
Abstract
- Specialized blood cells are generated through the entire life of an organism by differentiation of a small number of hematopoietic stem cells (HSC). There are strictly regulated mechanisms assuring a constant and controlled production of mature blood cells. Although such mechanisms are not completely understood, some factors regulating cell cycle and differentiation have been identified. We have previously shown that Caspase-3 is an important regulator of HSC homeostasis and cytokine responsiveness. p21cip1/waf1 is a known cell cycle regulator, however its role in stem cell homeostasis seems to be limited. Several reports indicate interactions between p21cip1/waf1 and Caspase-3 in a cell type dependent manner. Here we studied the impact of simultaneous depletion of both factors on HSC homeostasis. Depletion of both Caspase-3 and p21cip1/waf1 resulted in an even more pronounced increase in the frequency of hematopoietic stem and progenitor cells. In addition, simultaneous deletion of both genes revealed a further increase of cell proliferation compared to single knock-outs and WT control mice, while apoptosis or self-renewal ability were not affected in any of the genotypes. Upon transplantation, p21cip1/waf1-/- bone marrow did not reveal significant alterations in engraftment of lethally irradiated mice, while Caspase-3 deficient HSPC displayed a significant reduction of blood cell production. However, when both p21cip1/waf1 and Caspase-3 were eliminated this differentiation defect caused by Caspase-3 deficiency was abrogated.
- Subjects :
- Cyclin-Dependent Kinase Inhibitor p21
Cellular differentiation
lcsh:Medicine
Apoptosis
Bone Marrow Cells
Biology
Blood cell
Gene Knockout Techniques
Mice
Animal Cells
Bone Marrow Stem Cells
medicine
Animals
Cell Self Renewal
Progenitor cell
lcsh:Science
Molecular Biology
Cell Proliferation
Multidisciplinary
Caspase 3
Stem Cells
lcsh:R
Hematopoietic Stem Cell Transplantation
Biology and Life Sciences
Cell Differentiation
Cell Biology
Cell cycle
Hematopoietic Stem Cells
Cell biology
Endothelial stem cell
Adult Stem Cells
Haematopoiesis
medicine.anatomical_structure
Female
lcsh:Q
Bone marrow
Cellular Types
Stem cell
Gene Deletion
Signal Transduction
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....8c001f9c8c97ab32425aab07b0517363