Spen limits intestinal stem cell self-renewal

• Published in: PLoS genetics 2018-11, Vol.14 (11), p.e1007773
• Main Authors: Andriatsilavo, Maheva, Stefanutti, Marine, Siudeja, Katarzyna, Perdigoto, Carolina N, Boumard, Benjamin, Gervais, Louis, Gillet-Markowska, Alexandre, Al Zouabi, Lara, Schweisguth, François, Bardin, Allison J
• Format: Article
• Language: English
• Subjects: Adult Stem Cells - cytology; Adult Stem Cells - metabolism; Animals; Animals, Genetically Modified; Biology; Biology and Life Sciences; Cell Count; Cell Differentiation; Cell fate; Cell Lineage; Cell Proliferation; Cell Self Renewal - genetics; Cell Self Renewal - physiology; Cell self-renewal; Cellular Biology; Cloning; Drosophila; Drosophila melanogaster - cytology; Drosophila melanogaster - genetics; Drosophila melanogaster - physiology; Drosophila Proteins - antagonists & inhibitors; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Drosophila Proteins - physiology; Female; Gene expression; Gene Expression Regulation, Developmental; Gene regulation; Genes, Insect; Genetic aspects; Genetic regulation; Genetic research; Genetic screening; Genetic testing; Genomes; Homeodomain Proteins - antagonists & inhibitors; Homeodomain Proteins - genetics; Homeodomain Proteins - physiology; Homeostasis; Insects; Intestine; Intestines; Intestines - cytology; Life Sciences; Male; Medicine and Health Sciences; Models, Biological; Molecular modelling; Mutation; Nervous system; Neurosciences; Novels; Nuclear Proteins - antagonists & inhibitors; Nuclear Proteins - genetics; Nuclear Proteins - physiology; Ontology; Physiological aspects; Proteins; Receptors, Notch - metabolism; Research and Analysis Methods; Ribonucleic acid; RNA; RNA Interference; RNA-Binding Proteins; Signal Transduction; Software; Splicing; Stem cells; Transcription; Transcription (Genetics)
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1007773

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.