Essential role for Ptpn11 in survival of hematopoietic stem and progenitor cells

Item Type:	Article
Title:	Essential role for Ptpn11 in survival of hematopoietic stem and progenitor cells
Creators Name:	Chan, G. and Cheung, L.S. and Yang, W. and Milyavsky, M. and Sanders, A.D. and Gu, S. and Hong, W.X. and Liu, A.X. and Wang, X. and Barbara, M. and Sharma, T. and Gavin, J. and Kutok, J.L. and Iscove, N.N. and Shannon, K.M. and Dick, J.E. and Neel, B.G. and Braun, B.S.
Abstract:	Src homology 2 domain-containing phosphatase 2 (Shp2), encoded by Ptpn11, is a member of the nonreceptor protein-tyrosine phosphatase family, and functions in cell survival, proliferation, migration, and differentiation in many tissues. Here we report that loss of Ptpn11 in murine hematopoietic cells leads to bone marrow aplasia and lethality. Mutant mice show rapid loss of hematopoietic stem cells (HSCs) and immature progenitors of all hematopoietic lineages in a gene dosage-dependent and cell-autonomous manner. Ptpn11-deficient HSCs and progenitors undergo apoptosis concomitant with increased Noxa expression. Mutant HSCs/progenitors also show defective Erk and Akt activation in response to stem cell factor and diminished thrombopoietin-evoked Erk activation. Activated Kras alleviates the Ptpn11 requirement for colony formation by progenitors and cytokine/growth factor responsiveness of HSCs, indicating that Ras is functionally downstream of Shp2 in these cells. Thus, Shp2 plays a critical role in controlling the survival and maintenance of HSCs and immature progenitors in vivo.
Keywords:	Bone Marrow, Cell Cycle, Cell Death, Gene Deletion, Genetic Epistasis, Hematopoietic Stem Cells, Non-Receptor Type 11 Protein Tyrosine Phosphatase, Proto-Oncogene Proteins p21(ras), Stem Cells, Animals, Mice
Source:	Blood
ISSN:	0006-4971
Publisher:	American Society of Hematology
Volume:	117
Number:	16
Page Range:	4253-4261
Date:	21 April 2011
Official Publication:	https://doi.org/10.1182/blood-2010-11-319517
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

Repository Staff Only: item control page