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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: MPI-CBG Publications 2013 (arch)     Display Documents



ID: 688517.0, MPI für molekulare Zellbiologie und Genetik / MPI-CBG Publications 2013 (arch)
HIF prolyl hydroxylase 2 (PHD2) is a critical regulator of hematopoietic stem cell maintenance during steady-state and stress.
Authors:Singh, Rashim Pal; Franke, Kristin; Kalucka, Joanna; Mamlouk, Soulafa; Muschter, Antje; Gembarska, Agnieszka; Grinenko, Tatyana; Willam, Carsten; Naumann, Ronald; Anastassiadis, Konstantinos; Stewart, A Francis; Bornstein, Stefan; Chavakis, Trian; Breier, Georg; Waskow, Claudia; Wielockx, Ben
Date of Publication (YYYY-MM-DD):2013
Title of Journal:Blood
Volume:121
Issue / Number:26
Start Page:5158
End Page:5166
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Hypoxia is a prominent feature in the maintenance of hematopoietic stem cell (HSC) quiescence and multipotency. Hypoxia-inducible factor (HIF) prolyl hydroxylase domain proteins (PHDs) serve as oxygen sensors and may therefore regulate this system. Here, we describe a mouse line with conditional loss of HIF prolyl hydroxylase 2 (PHD2) in very early hematopoietic precursors that results in self-renewal of multipotent progenitors under steady-state conditions in a HIF1α- and SMAD7-dependent manner. Competitive bone marrow (BM) transplantations show decreased peripheral and central chimerism of PHD2-deficient cells but not of the most primitive progenitors. Conversely, in whole BM transfer, PHD2-deficient HSCs replenish the entire hematopoietic system and display an enhanced self-renewal capacity reliant on HIF1α. Taken together, our results demonstrate that loss of PHD2 controls the maintenance of the HSC compartment under physiological conditions and causes the outcompetition of PHD2-deficient hematopoietic cells by their wild-type counterparts during stress while promoting the self-renewal of very early hematopoietic progenitors.
External Publication Status:published
Document Type:Article
Communicated by:Lib
Affiliations:MPI für molekulare Zellbiologie und Genetik
Identifiers:LOCALID:5640
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