GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE277nnn/GSE277603/primaryOK200TranscriptomicsMus musculus synthetic construct OtherExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE277603GEOGSEfalseDifferential IRES-initiated translation during homeostatic stem cell differentiation and stressCell stress commonly induces preferentially reduced m7G-cap-dependent translation initiation while cap-indendepent, IRES-mediated initiation persists. We investigated differential translation initiation in the highly regulated protein production of somatic stem cells by generating a reporter mouse quantifying the ratio of IRES-mediated to cap-dependent translation in vivo. Both hematopoietic and epithelial stem cells exhibited minimal IRES utilization that progressively increased with differentiation. Notably, even within defined differentiation states, lower IRES/Cap was associated with increased clonogenicity regardless of cell cycle and among HSCs, with greater long-term multi-lineage regeneration. The RNA binding protein PTBP1 is a key modulator of IRES utilization during differentiation by CRISPR/Cas9i screening. Even within IRES-low immature stem/progenitor cells, nutrient stress upregulated IRES utilization, pointing to distinct roles of IRES in cell behavior depending on physiologic state.2026/04/02GSE277603GSM8525881GSM8525882GSM8525860GSM8525883GSM8525861GSM8525862GSM8525884GSM8525885GSM8525863GSM8525886GSM8525864GSM8525865GSM8525887GSM8525888GSM8525866GSM8525889GSM8525867GSM8525868GSM8525869GSM8525880GSM8525870GSM8525892GSM8525893GSM8525871GSM8525872GSM8525873GSM8525874GSM8525875GSM8525876GSM8525877GSM8525878GSM8525879GSM8525858GSM8525859GSM8525890GSM85258911905715228277603Mus musculus synthetic construct