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PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention.

Abstract：

:Haematopoietic stem cells (HSCs) must achieve a balance between quiescence and activation that fulfils immediate demands for haematopoiesis without compromising long-term stem cell maintenance, yet little is known about the molecular events governing this balance. Phosphatase and tensin homologue (PTEN) functions as a negative regulator of the phosphatidylinositol-3-OH kinase (PI(3)K)-Akt pathway, which has crucial roles in cell proliferation, survival, differentiation and migration. Here we show that inactivation of PTEN in bone marrow HSCs causes their short-term expansion, but long-term decline, primarily owing to an enhanced level of HSC activation. PTEN-deficient HSCs engraft normally in recipient mice, but have an impaired ability to sustain haematopoietic reconstitution, reflecting the dysregulation of their cell cycle and decreased retention in the bone marrow niche. Mice with PTEN-mutant bone marrow also have an increased representation of myeloid and T-lymphoid lineages and develop myeloproliferative disorder (MPD). Notably, the cell populations that expand in PTEN mutants match those that become dominant in the acute myeloid/lymphoid leukaemia that develops in the later stages of MPD. Thus, PTEN has essential roles in restricting the activation of HSCs, in lineage fate determination, and in the prevention of leukaemogenesis.

journal_name

Nature

journal_title

Nature

authors

Zhang J,Grindley JC,Yin T,Jayasinghe S,He XC,Ross JT,Haug JS,Rupp D,Porter-Westpfahl KS,Wiedemann LM,Wu H,Li L

doi

10.1038/nature04747

subject

Has Abstract

pub_date

2006-05-25 00:00:00

pages

518-22

issue

7092

eissn

0028-0836

issn

1476-4687

pii

nature04747

journal_volume

441

pub_type

杂志文章

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