Modest Declines in Proteome Quality Impair Hematopoietic Stem Cell Self-Renewal.

ABSTRACT: Low protein synthesis is a feature of somatic stem cells that promotes regeneration in multiple tissues. Modest increases in protein synthesis impair stem cell function, but the mechanisms by which this occurs are largely unknown. We determine that low protein synthesis within hematopoietic stem cells (HSCs) is associated with elevated proteome quality in vivo. HSCs contain less misfolded and unfolded proteins than myeloid progenitors. Increases in protein synthesis cause HSCs to accumulate misfolded and unfolded proteins. To test how proteome quality affects HSCs, we examine Aars^sti/sti mice that harbor a tRNA editing defect that increases amino acid misincorporation. Aars^sti/sti mice exhibit reduced HSC numbers, increased proliferation, and diminished serial reconst

SUBMITTER: Hidalgo San Jose L 

PROVIDER: S-EPMC7004491 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature