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Prion protein deficiency impairs hematopoietic stem cells determination and sensitizes myeloid progenitors to irradiation


Siberchicot, Capucine; Gault, Nathalie; Déchamps, Nathalie; Barroca, Vilma; Aguzzi, Adriano; Roméo, Paul-Henri; Radicella, J Pablo; Bravard, Anne; Bernardino-Sgherri, Jacqueline (2019). Prion protein deficiency impairs hematopoietic stem cells determination and sensitizes myeloid progenitors to irradiation. Haematologica:Epub ahead of print.

Abstract

Highly conserved among species and expressed in various types of cells, numerous roles have been attributed to the cellular prion protein (PrPC). In hematopoiesis, PrPC regulates hematopoietic stem cells self-renewal but the mechanisms involved in this regulation are unknown. Here we show that PrPC regulates hematopoietic stem cells number during aging and their determination towards myeloid progenitors. Furthermore, PrPC protects myeloid progenitors against the cytotoxic effects of total body irradiation. This radioprotective effect was associated with increased cellular prion mRNA level and with stimulation of the DNA repair activity of the Apurinic/pyrimidinic endonuclease 1, a key enzyme of the base excision repair pathway. Altogether, these results show a previously unappreciated role of PrPC in adult hematopoiesis and indicate that PrPC mediated stimulation of BER activity might protect hematopoietic progenitors from the cytototic effects of total body irradiation.

Abstract

Highly conserved among species and expressed in various types of cells, numerous roles have been attributed to the cellular prion protein (PrPC). In hematopoiesis, PrPC regulates hematopoietic stem cells self-renewal but the mechanisms involved in this regulation are unknown. Here we show that PrPC regulates hematopoietic stem cells number during aging and their determination towards myeloid progenitors. Furthermore, PrPC protects myeloid progenitors against the cytotoxic effects of total body irradiation. This radioprotective effect was associated with increased cellular prion mRNA level and with stimulation of the DNA repair activity of the Apurinic/pyrimidinic endonuclease 1, a key enzyme of the base excision repair pathway. Altogether, these results show a previously unappreciated role of PrPC in adult hematopoiesis and indicate that PrPC mediated stimulation of BER activity might protect hematopoietic progenitors from the cytototic effects of total body irradiation.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Uncontrolled Keywords:Hematology
Language:English
Date:1 August 2019
Deposited On:21 Aug 2019 07:43
Last Modified:27 Nov 2019 14:35
Publisher:Ferrata Storti Foundation
ISSN:0390-6078
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.3324/haematol.2018.205716

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