Open AccessSpen limits intestinal stem cell self-renewal
Author(s) -
Mahéva Andriatsilavo,
Marine Stefanutti,
Katarzyna Siudeja,
Caroli. Perdigoto,
Benjamin Boumard,
Louis Gervais,
Alexandre Gillet-Markowska,
Lara Al zouabi,
François Schweisguth,
Allison J. Bardin
Publication year - 2018
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1007773
Subject(s) - biology , stem cell , microbiology and biotechnology , regulator , cellular differentiation , rna splicing , exon , rna binding protein , alternative splicing , gene , regulation of gene expression , rna , genetics , computational biology
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.