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PLoS Genet. 2018 Nov 19;14(11):e1007773. doi: 10.1371/journal.pgen.1007773. eCollection 2018 Nov.

Spen limits intestinal stem cell self-renewal.

Author information

Institut Curie, PSL Research University, CNRS UMR 3215, INSERM U934, Stem Cells and Tissue Homeostasis group, Sorbonne Université, UPMC Univ Paris 6, Paris, France.
Discngine, Paris, France.
Institut Pasteur, Dept of Developmental and Stem Cell Biology, Paris, France.
CNRS, UMR3738, Paris, France.


Precise regulation of stem cell self-renewal and differentiation properties is essential for tissue homeostasis. Using the adult Drosophila intestine to study molecular mechanisms controlling stem cell properties, we identify the gene split-ends (spen) in a genetic screen as a novel regulator of intestinal stem cell fate (ISC). Spen family genes encode conserved RNA recognition motif-containing proteins that are reported to have roles in RNA splicing and transcriptional regulation. We demonstrate that spen acts at multiple points in the ISC lineage with an ISC-intrinsic function in controlling early commitment events of the stem cells and functions in terminally differentiated cells to further limit the proliferation of ISCs. Using two-color cell sorting of stem cells and their daughters, we characterize spen-dependent changes in RNA abundance and exon usage and find potential key regulators downstream of spen. Our work identifies spen as an important regulator of adult stem cells in the Drosophila intestine, provides new insight to Spen-family protein functions, and may also shed light on Spen's mode of action in other developmental contexts.

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