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@ARTICLE{Wang:299792,
author = {R. Wang and M. Roiuk$^*$ and F. Storer and A. A.
Teleman$^*$ and M. Amoyel},
title = {{S}ignals from the niche promote distinct modes of
translation initiation to control stem cell differentiation
and renewal in the {D}rosophila testis.},
journal = {PLoS biology},
volume = {23},
number = {3},
issn = {1544-9173},
address = {Lawrence, KS},
publisher = {PLoS},
reportid = {DKFZ-2025-00547},
pages = {e3003049 -},
year = {2025},
abstract = {Stem cells have the unique ability among adult cells to
give rise to cells of different identities. To do so, they
must change gene expression in response to environmental
signals. Much work has focused on how transcription is
regulated to achieve these changes; however, in many cell
types, transcripts and proteins correlate poorly, indicating
that post-transcriptional regulation is important. To assess
how translational control can influence stem cell fate, we
use the Drosophila testis as a model. The testis niche
secretes a ligand to activate the Janus kinase (JAK)/signal
transducer and activator of transcription (STAT) pathway in
two stem cell populations, germline stem cells (GSCs) and
somatic cyst stem cells (CySCs). We find that global
translation rates are high in CySCs and decrease during
differentiation, and that JAK/STAT signaling regulates
translation. To determine how translation was regulated, we
knocked down translation initiation factors and found that
the cap binding complex, eIF4F, is dispensable in
differentiating cells, but is specifically required in CySCs
for self-renewal, acting downstream of JAK/STAT activity.
Moreover, we identify eIF3d1 as a key regulator of CySC
fate, and show that two eIF3d1 residues subject to
regulation by phosphorylation are critical to maintain CySC
self-renewal. We further show that Casein Kinase II (CkII),
which controls eIF3d1 phosphorylation, influences the
binding of eIF3d and eIF4F in mammalian cells, and that CkII
expression is sufficient to restore CySC function in the
absence of JAK/STAT. We propose a model in which niche
signals regulate a specific translation programme in which
only some mRNAs are translated. The mechanism we identify
allows stem cells to switch between modes of translation,
adding a layer of regulation on top of transcription and
providing cells with the ability to rapidly change gene
expression upon receiving external stimuli.},
cin = {B140},
ddc = {610},
cid = {I:(DE-He78)B140-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40067813},
doi = {10.1371/journal.pbio.3003049},
url = {https://inrepo02.dkfz.de/record/299792},
}