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

Hematopoietic Stem Cells Humans Myeloid Progenitor Cells Prion Proteins / genetics Prions / genetics Protein Deficiency

Journal

Haematologica
ISSN: 1592-8721
Titre abrégé: Haematologica
Pays: Italy
ID NLM: 0417435

Informations de publication

Date de publication:
05 2020
Historique:
received: 03 09 2018
accepted: 15 07 2019
pubmed: 3 8 2019
medline: 28 4 2021
entrez: 3 8 2019
Statut: ppublish

Résumé

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 cell self-renewal but the mechanisms involved in this regulation are unknown. Here we show that PrPC regulates hematopoietic stem cell 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 cytotoxic effects of total body irradiation.

Identifiants

DOI: 10.3324/haematol.2018.205716 PMID: 31371412 PMC: PMC7193476
pubmed: 31371412
pii: haematol.2018.205716
doi: 10.3324/haematol.2018.205716
pmc: PMC7193476
doi:

Substances chimiques

Prion Proteins 0
Prions 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1216-1222

Informations de copyright

Copyright© 2020 Ferrata Storti Foundation.

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Auteurs

Capucine Siberchicot (C)

French Alternative Energies and Atomic Energy Commission (CEA)/Direction of Fundamental Research (DRF)/Institute of Biology François Jacob (IBFJ)/Institute of Cellular and Molecular Radiobiology (iRCM), 92265 Fontenay-aux-Roses Cedex, France.
Laboratory of Research in Genetic Instability (LRIG), 92265 Fontenay-aux-Roses Cedex, France.
Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.
Université Paris-Sud, Paris, France.

Nathalie Gault (N)

French Alternative Energies and Atomic Energy Commission (CEA)/Direction of Fundamental Research (DRF)/Institute of Biology François Jacob (IBFJ)/Institute of Cellular and Molecular Radiobiology (iRCM), 92265 Fontenay-aux-Roses Cedex, France.
Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.
Université Paris-Sud, Paris, France.
Laboratory of Repair and Transcription in Hematopoietic Stem Cells (LRTS), 92265 Fontenay-aux-Roses Cedex, France.
Inserm U967, 92265 Fontenay-aux-Roses Cedex, France.

Nathalie Déchamps (N)

French Alternative Energies and Atomic Energy Commission (CEA)/Direction of Fundamental Research (DRF)/Institute of Biology François Jacob (IBFJ)/Institute of Cellular and Molecular Radiobiology (iRCM), 92265 Fontenay-aux-Roses Cedex, France.
Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.
Université Paris-Sud, Paris, France.
Inserm U967, 92265 Fontenay-aux-Roses Cedex, France.

Vilma Barroca (V)

French Alternative Energies and Atomic Energy Commission (CEA)/Direction of Fundamental Research (DRF)/Institute of Biology François Jacob (IBFJ)/Institute of Cellular and Molecular Radiobiology (iRCM), 92265 Fontenay-aux-Roses Cedex, France.
Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.
Université Paris-Sud, Paris, France.
Laboratory of Repair and Transcription in Hematopoietic Stem Cells (LRTS), 92265 Fontenay-aux-Roses Cedex, France.
Inserm U967, 92265 Fontenay-aux-Roses Cedex, France.

Adriano Aguzzi (A)

Institute of Neuropathology, University of Zurich, Zurich, Switzerland.

Paul-Henri Roméo (PH)

French Alternative Energies and Atomic Energy Commission (CEA)/Direction of Fundamental Research (DRF)/Institute of Biology François Jacob (IBFJ)/Institute of Cellular and Molecular Radiobiology (iRCM), 92265 Fontenay-aux-Roses Cedex, France.
Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.
Université Paris-Sud, Paris, France.
Laboratory of Repair and Transcription in Hematopoietic Stem Cells (LRTS), 92265 Fontenay-aux-Roses Cedex, France.
Inserm U967, 92265 Fontenay-aux-Roses Cedex, France.

J Pablo Radicella (JP)

French Alternative Energies and Atomic Energy Commission (CEA)/Direction of Fundamental Research (DRF)/Institute of Biology François Jacob (IBFJ)/Institute of Cellular and Molecular Radiobiology (iRCM), 92265 Fontenay-aux-Roses Cedex, France.
Laboratory of Research in Genetic Instability (LRIG), 92265 Fontenay-aux-Roses Cedex, France.
Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.
Université Paris-Sud, Paris, France.

Anne Bravard (A)

French Alternative Energies and Atomic Energy Commission (CEA)/Direction of Fundamental Research (DRF)/Institute of Biology François Jacob (IBFJ)/Institute of Cellular and Molecular Radiobiology (iRCM), 92265 Fontenay-aux-Roses Cedex, France jacqueline.bernardino@cea.fr anne.bravard@cea.fr.
Laboratory of Research in Genetic Instability (LRIG), 92265 Fontenay-aux-Roses Cedex, France.
Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.
Université Paris-Sud, Paris, France.
Laboratory of Repair and Transcription in Hematopoietic Stem Cells (LRTS), 92265 Fontenay-aux-Roses Cedex, France.
Inserm U967, 92265 Fontenay-aux-Roses Cedex, France.

Jacqueline Bernardino-Sgherri (J)

French Alternative Energies and Atomic Energy Commission (CEA)/Direction of Fundamental Research (DRF)/Institute of Biology François Jacob (IBFJ)/Institute of Cellular and Molecular Radiobiology (iRCM), 92265 Fontenay-aux-Roses Cedex, France jacqueline.bernardino@cea.fr anne.bravard@cea.fr.
Laboratory of Research in Genetic Instability (LRIG), 92265 Fontenay-aux-Roses Cedex, France.
Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.
Université Paris-Sud, Paris, France.
Laboratory of Repair and Transcription in Hematopoietic Stem Cells (LRTS), 92265 Fontenay-aux-Roses Cedex, France.
Inserm U967, 92265 Fontenay-aux-Roses Cedex, France.

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Classifications MeSH

questionsmedicales.fr › Systèmes sanguin et immunitaire › Système hématopoïétique › Cellules de la moelle osseuse › Cellules souches hématopoïétiques › Prion protein deficiency impairs hematopoietic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Prion protein deficiency impairs hematopoietic...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système hématopoïétique › Cellules de la moelle osseuse › Cellules souches hématopoïétiques › Progéniteurs myéloïdes › Prion protein deficiency impairs hematopoietic...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Prions › Protéines prion › Prion protein deficiency impairs hematopoietic...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Prions › Prion protein deficiency impairs hematopoietic...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Troubles nutritionnels › Malnutrition › Maladies de carence › Carence protéique › Prion protein deficiency impairs hematopoietic...