The E3 ligase Itch is a negative regulator of the homeostasis and function of hematopoietic stem cells | Zendy

Chozhavendan Rathinam | Zendy; Lydia E. Matesic | Zendy; Richard A. Flavell | Zendy

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The E3 ligase Itch is a negative regulator of the homeostasis and function of hematopoietic stem cells

Author(s) -

Chozhavendan Rathinam,

Lydia E. Matesic,

Richard A. Flavell

Publication year - 2011

Publication title -

nature immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 9.074

H-Index - 388

eISSN - 1529-2916

pISSN - 1529-2908

DOI - 10.1038/ni.2021

Subject(s) - ubiquitin ligase , stem cell , haematopoiesis , microbiology and biotechnology , regulator , biology , ubiquitin , progenitor cell , gene knockdown , transcription factor , hematopoietic stem cell , homeostasis , phenotype , genetics , cell culture , gene

Although hematopoietic stem cells (HSCs) are the most thoroughly characterized type of adult stem cell, the intricate molecular machinery that regulates their self-renewal properties remains elusive. Here we showed that the E3 ubiquitin ligase Itch negatively regulated the development and function of HSCs. Itch(-/-) mice had HSCs with enhanced frequency, competence and long-term repopulating activity. Itch-deficient HSCs showed accelerated proliferation rates and sustained progenitor properties, as well as more signaling by the transcription factor Notch1, due to more accumulation of activated Notch1. Knockdown of Notch1 in Itch-mutant HSCs resulted in reversion of the phenotype. Thus, we identify Itch as a previously unknown negative regulator of HSC homeostasis and function.

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