A latent subset of human hematopoietic ...
Type de document :
Article dans une revue scientifique: Article original
PMID :
URL permanente :
Titre :
A latent subset of human hematopoietic stem cells resists regenerative stress to preserve stemness
Auteur(s) :
Kaufmann, Kerstin B. [Auteur]
Zeng, Andy G. X. [Auteur]
Coyaud, Etienne-Marie [Auteur]
Princess Margaret Hospital
Garcia-Prat, Laura [Auteur]
Papalexi, Efthymia [Auteur]
Murison, Alex [Auteur]
Laurent, Estelle [Auteur]
Ontario Institute for Cancer Research [Canada] [OICR]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Chan-Seng-Yue, Michelle [Auteur]
Gan, Olga I. [Auteur]
Pan, Kristele [Auteur]
Mcleod, Jessica [Auteur]
Boutzen, Helena [Auteur]
Zandi, Sasan [Auteur]
Takayanagi, Shin-Ichiro [Auteur]
Satija, Rahul [Auteur]
Raught, Brian [Auteur]
Xie, Stephanie Z. [Auteur]
Dick, John E. [Auteur]
Zeng, Andy G. X. [Auteur]
Coyaud, Etienne-Marie [Auteur]
Princess Margaret Hospital
Garcia-Prat, Laura [Auteur]
Papalexi, Efthymia [Auteur]
Murison, Alex [Auteur]
Laurent, Estelle [Auteur]
Ontario Institute for Cancer Research [Canada] [OICR]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Chan-Seng-Yue, Michelle [Auteur]
Gan, Olga I. [Auteur]
Pan, Kristele [Auteur]
Mcleod, Jessica [Auteur]
Boutzen, Helena [Auteur]
Zandi, Sasan [Auteur]
Takayanagi, Shin-Ichiro [Auteur]
Satija, Rahul [Auteur]
Raught, Brian [Auteur]
Xie, Stephanie Z. [Auteur]
Dick, John E. [Auteur]
Titre de la revue :
Nature Immunology
Nom court de la revue :
Nat Immunol
Numéro :
22
Pagination :
723-734
Date de publication :
2021-05-06
ISSN :
1529-2916
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Continuous supply of immune cells throughout life relies on the delicate balance in the hematopoietic stem cell (HSC) pool between long-term maintenance and meeting the demands of both normal blood production and unexpected ...
Lire la suite >Continuous supply of immune cells throughout life relies on the delicate balance in the hematopoietic stem cell (HSC) pool between long-term maintenance and meeting the demands of both normal blood production and unexpected stress conditions. Here we identified distinct subsets of human long-term (LT)-HSCs that responded differently to regeneration-mediated stress: an immune checkpoint ligand CD112(lo) subset that exhibited a transient engraftment restraint (termed latency) before contributing to hematopoietic reconstitution and a primed CD112(hi) subset that responded rapidly. This functional heterogeneity and CD112 expression are regulated by INKA1 through direct interaction with PAK4 and SIRT1, inducing epigenetic changes and defining an alternative state of LT-HSC quiescence that serves to preserve self-renewal and regenerative capacity upon regeneration-mediated stress. Collectively, our data uncovered the molecular intricacies underlying HSC heterogeneity and self-renewal regulation and point to latency as an orchestrated physiological response that balances blood cell demands with preserving a stem cell reservoir.Lire moins >
Lire la suite >Continuous supply of immune cells throughout life relies on the delicate balance in the hematopoietic stem cell (HSC) pool between long-term maintenance and meeting the demands of both normal blood production and unexpected stress conditions. Here we identified distinct subsets of human long-term (LT)-HSCs that responded differently to regeneration-mediated stress: an immune checkpoint ligand CD112(lo) subset that exhibited a transient engraftment restraint (termed latency) before contributing to hematopoietic reconstitution and a primed CD112(hi) subset that responded rapidly. This functional heterogeneity and CD112 expression are regulated by INKA1 through direct interaction with PAK4 and SIRT1, inducing epigenetic changes and defining an alternative state of LT-HSC quiescence that serves to preserve self-renewal and regenerative capacity upon regeneration-mediated stress. Collectively, our data uncovered the molecular intricacies underlying HSC heterogeneity and self-renewal regulation and point to latency as an orchestrated physiological response that balances blood cell demands with preserving a stem cell reservoir.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
INSERM
Université de Lille
Université de Lille
Collections :
Date de dépôt :
2022-06-15T13:58:13Z
2023-04-05T09:10:22Z
2023-04-05T09:10:22Z
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