Charting and probing the activity of ADARs in human development and cell-fate specification

Charting and probing the activity of ADARs in human development and cell-fate specification

Blog Article

Abstract Adenosine keychron m4 deaminases acting on RNA (ADARs) impact diverse cellular processes and pathological conditions, but their functions in early cell-fate specification remain less understood.To gain insights here, we began by charting time-course RNA editing profiles in human organs from fetal to adult stages.Next, we utilized hPSC differentiation to experimentally probe ADARs, harnessing brain organoids as neural specific, and teratomas as pan-tissue developmental models.We show that time-series teratomas faithfully recapitulate fetal developmental trends, and motivated by this, conducted pan-tissue, single-cell CRISPR-KO screens of ADARs in teratomas.Knocking out ADAR leads to a global decrease in RNA editing across all germ-layers.

Intriguingly, knocking out ADAR leads to an enrichment of adipogenic cells, revealing a role for ADAR in human adipogenesis.Collectively, we present a multi-pronged framework charting time-resolved RNA editing profiles and coupled ADAR opheliasmuse.com perturbations in developmental models, thereby shedding light on the role of ADARs in cell-fate specification.