A cascade of RNA binding proteins controls the switch from proliferation to differentiation in an adult stem cell lineage [RNA-Seq]

ABSTRACT: ABSTRACT: The mechanisms that regulate the switch from precursor cell proliferation to onset of differentiation in the adult stem cell lineages that maintain or repair many tissues in the body must be carefully regulated to assure production of sufficient progeny to maintain tissues yet prevent overproliferation that may lead to oncogenic progression. We are investigating the mechanisms regulating the switch from transit amplifying divisions to onset of differentiation in the Drosophila male germ line adult stem cell lineage, where spermatogonia undergo a limited number of mitotic divisions before switching to the spermatocyte program that sets up differentiation and meiosis. The number of transit amplifying spermatogonia divisions is set by accumulation of the Bag of marbles (Bam) protein to a critical threshold. Here we identify repression of Held Out Wings (how), homolog of mammalian Quaking, as the key target of Bam enabling the mitosis to differentiation switch. Knock down of how in germ cells was sufficient to allow spermatogonia mutant for bam or its partner bgcn to differentiate, while forced expression of nuclear-targeted How protein in otherwise wild-type spermatogonia resulted in continued proliferation of spermatogonia at the expense of differentiation. Our findings suggest that Bam targets how RNA for degradation by acting as an adapter to recruit the CCR4-NOT deadenylation complex via binding its subunit, Caf40. Our data support the model that the switch from proliferation to differentiation in this model adult stem cell lineage is regulated by a cascade of RNA-binding proteins.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE274383 | GEO | 2025/06/04

REPOSITORIES: GEO