Transcriptomics

Dataset Information

0

ID2 and HIF-1α Collaborate to Protect Quiescent Hematopoietic Stem Cells from Activation, Differentiation and Exhaustion [RNA-seq]


ABSTRACT: Defining mechanism(s) that maintain tissue stem quiescence is important for improving tissue regeneration, cell therapies, aging, and cancer. We report here that genetic ablation of Id2 in adult hematopoietic stem cells (HSCs) promotes increased HSC activation and differentiation, which results in HSC exhaustion and bone marrow failure over time. Id2Δ/Δ HSCs show increased HSC cycling, reactive oxygen species (ROS) production, mitochondrial activation, and DNA damage supporting the conclusion that Id2Δ/Δ HSCs are less quiescent. Mechanistically, HIF-1α expression is decreased in Id2Δ/Δ HSCs, and stabilization of HIF-1α in Id2Δ/Δ HSCs restores HSC quiescence and rescues HSC exhaustion. ID2 promotes HIF-1α expression by binding to the Von Hippel-Lindau (VHL) protein and interfering with proteasomal degradation of HIF-1α. HIF-1α promotes Id2 expression and enforces a positive feedback loop between ID2 and HIF-1α to maintain HSC quiescence. Thus, sustained ID2 expression could protect HSCs during stress, and improve HSC expansion for gene editing and cell therapies.

ORGANISM(S): Mus musculus

PROVIDER: GSE203076 | GEO | 2022/05/31

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2022-05-31 | GSE205102 | GEO
2022-11-11 | GSE191162 | GEO
2022-11-11 | GSE191161 | GEO
2017-09-13 | PXD006054 | Pride
2024-06-03 | GSE230711 | GEO
2014-03-14 | E-GEOD-45194 | biostudies-arrayexpress
2022-11-16 | GSE199936 | GEO
2022-11-16 | GSE199935 | GEO
2022-11-16 | GSE199934 | GEO
2022-12-22 | GSE219050 | GEO