NFAT5 counters long-term IFN-1 responses in hematopoietic stem cells to preserve reconstitution potential.

ABSTRACT:

Abstract

Hematopoietic stem cells (HSCs) readily recover from acute stress, but persistent stress can reduce their viability and long-term potential. Here, we show that the nuclear factor of activated T cells 5 (NFAT5), a transcription modulator of inflammatory responses, protects the HSC pool under stress. NFAT5 restrains HSC differentiation to multipotent progenitors after bone marrow transplantation and bone marrow ablation with ionizing radiation or chemotherapy. Correspondingly, NFAT5-deficient HSCs fail to support long-term reconstitution of hematopoietic progenitors and mature blood cells after serial transplant. Evidence from competitive transplant assays shows that these defects are HSC intrinsic. NFAT5-deficient HSCs exhibit enhanced expression of type 1 interferon (IFN-1

SUBMITTER: Traveset L 

PROVIDER: S-EPMC11538617 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature