title: Escargot maintains stemness and suppresses differentiation in Drosophila intestinal stem cells.
abstract: Snail family transcription factors are expressed in various stem cell types, but their function in maintaining stem cell identity is unclear. In the adult Drosophila midgut, the Snail homolog Esg is expressed in intestinal stem cells (ISCs) and their transient undifferentiated daughters, termed enteroblasts (EB). We demonstrate here that loss of esg in these progenitor cells causes their rapid differentiation into enterocytes (EC) or entero-endocrine cells (EE). Conversely, forced expression of Esg in intestinal progenitor cells blocks differentiation, locking ISCs in a stem cell state. Cell type-specific transcriptome analysis combined with Dam-ID binding studies identified Esg as a major repressor of differentiation genes in stem and progenitor cells. One critical target of Esg was found to be the POU-domain transcription factor, Pdm1, which is normally expressed specifically in differentiated ECs. Ectopic expression of Pdm1 in progenitor cells was sufficient to drive their differentiation into ECs. Hence, Esg is a critical stem cell determinant that maintains stemness by repressing differentiation-promoting factors, such as Pdm1.
authors.affiliation: DKFZ/ZMBH Alliance, University of Heidelberg, Heidelberg, Germany.
authors.forename: Jerome
authors.initials: J
authors.lastname: Korzelius
authors.affiliation: DKFZ/ZMBH Alliance, University of Heidelberg, Heidelberg, Germany.
authors.forename: Svenja K
authors.initials: SK
authors.lastname: Naumann
authors.affiliation: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA Department of Molecular, Cell, and Developmental Biology, University of California-Los Angeles, Los Angeles, CA, USA.
authors.forename: Mariano A
authors.initials: MA
authors.lastname: Loza-Coll
authors.affiliation: DKFZ/ZMBH Alliance, University of Heidelberg, Heidelberg, Germany.
authors.forename: Jessica Sk
authors.initials: JS
authors.lastname: Chan
authors.affiliation: DKFZ/ZMBH Alliance, University of Heidelberg, Heidelberg, Germany.
authors.forename: Devanjali
authors.initials: D
authors.lastname: Dutta
authors.affiliation: DKFZ/ZMBH Alliance, University of Heidelberg, Heidelberg, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Oberheim
authors.affiliation: DKFZ/ZMBH Alliance, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Gläßer
authors.affiliation: The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Tony D
authors.initials: TD
authors.lastname: Southall
authors.affiliation: The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Andrea H
authors.initials: AH
authors.lastname: Brand
authors.affiliation: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA Department of Molecular, Cell, and Developmental Biology, University of California-Los Angeles, Los Angeles, CA, USA.
authors.forename: D Leanne
authors.initials: DL
authors.lastname: Jones
authors.affiliation: DKFZ/ZMBH Alliance, University of Heidelberg, Heidelberg, Germany b.edgar@Dkfz-Heidelberg.de.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Edgar
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000502:physiology; D017353:Gene Deletion; D015870:Gene Expression; D020869:Gene Expression Profiling; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; C467520:esg protein, Drosophila
keywords: Drosophila midgut; Pdm1; Snail transcription factors; enterocyte differentiation; intestinal stem cells