Title :

A latent subset of human hematopoietic stem cells resists regenerative stress to preserve stemness

Author(s) :

Kaufmann, Kerstin B. [Auteur]
Zeng, Andy G. X. [Auteur]
Coyaud, Etienne-Marie [Auteur]
Garcia-Prat, Laura [Auteur]
Papalexi, Efthymia [Auteur]
Murison, Alex [Auteur]
Laurent, Estelle [Auteur]
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]

Journal title :

Nature immunology

Abbreviated title :

Nat Immunol

Publication date :

2021-05-06

ISSN :

1529-2916

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [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 ...
Show more >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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

INSERM
Université de Lille

Collections :

• Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Submission date :

2022-06-15T13:58:13Z