RNA-seq on dual-FACS sorted Drosophila Intestinal stem cell and Enteroblast, and effect of SPEN loss of function on gene expression

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. 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 loss of function in intestinal stem cells results in an abnormal increase in the number of stem cell-like cells and that Spen acts to control early commitment events of the stem cells. 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. Overall design: Three biological replicates were sequenced per each 4 conditions

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Andriatsilavo M, Stefanutti M, Siudeja K, Perdigoto CN, Boumard B, Gervais L, Gillet-Markowska A, Al Zouabi L, Schweisguth F, Bardin AJ