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Singh, R.P.* ; Franke, K.* ; Kalucka, J.* ; Mamlouk, S.* ; Muschter, A.* ; Gembarska, A.* ; Grinenko, T.* ; Willam, C.* ; Naumann, R.* ; Anastassiadis, K.* ; Stewart, A.F.* ; Bornstein, S.R.* ; Chavakis, T.* ; Breier, G.* ; Waskow, C.* ; Wielockx, B.*

HIF prolyl hydroxylase 2 (PHD2) is a critical regulator of hematopoietic stem cell maintenance during steady-state and stress.

Blood 121, 5158-5166 (2013)
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Zeitschrift Blood
Quellenangaben Band: 121, Heft: 26, Seiten: 5158-5166 Artikelnummer: , Supplement: ,
Verlag American Society of Hematology
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)