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Journal Article

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

MPS-Authors
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Franke,  Kristin
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Kalucka,  Joanna
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

Mamlouk,  Soulafa
Max Planck Society;

Muschter,  Antje
Max Planck Society;

Gembarska,  Agnieszka
Max Planck Society;

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Naumann,  Ronald
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

Anastassiadis,  Konstantinos
Max Planck Society;

Bornstein,  Stefan
Max Planck Society;

Chavakis,  Trian
Max Planck Society;

Breier,  Georg
Max Planck Society;

Waskow,  Claudia
Max Planck Society;

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Citation

Singh, R. P., Franke, K., Kalucka, J., Mamlouk, S., Muschter, A., Gembarska, A., et al. (2013). HIF prolyl hydroxylase 2 (PHD2) is a critical regulator of hematopoietic stem cell maintenance during steady-state and stress. Blood, 121(26), 5158-5166.


Cite as: https://hdl.handle.net/21.11116/0000-0001-06E4-7
Abstract
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.