Escargot maintains stemness and suppresses differentiation in Drosophila intestinal stem cells

• Published in: The EMBO journal 2014-12, Vol.33 (24), p.2967-2982
• Main Authors: Korzelius, Jerome, Naumann, Svenja K, Loza-Coll, Mariano A, Chan, Jessica SK, Dutta, Devanjali, Oberheim, Jessica, Gläßer, Christine, Southall, Tony D, Brand, Andrea H, Jones, D Leanne, Edgar, Bruce A
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation; Drosophila - physiology; Drosophila midgut; Drosophila Proteins - metabolism; EMBO11; EMBO39; EMBO44; enterocyte differentiation; Gastrointestinal Tract - physiology; Gene Deletion; Gene Expression; Gene Expression Profiling; Genes; Insects; intestinal stem cells; Mollusks; Pdm1; Snail transcription factors; Stem cells; Stem Cells - drug effects; Stem Cells - physiology; Transcription factors
• ISSN: 0261-4189; 1460-2075
• DOI: 10.15252/embj.201489072

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. Synopsis This paper unravels the functionality of Escargot, so far described as marker for progenitors cells in Drosophila , in intestinal stem cell maintenance and suppressor of differentiation. Esg is required to maintain intestinal stem cell identity. Esg acts as a repressor of differentiation genes in progenitor cells. Pdm1 is a direct target of Esg that is sufficient to trigger EC differentiation. Esg, Notch and Pdm1 function together in a transcriptional network that controls differentiation in the Drosophila midgut. Graphical Abstract This paper unravels the functionality of Escargot, so far described as marker for progenitors cells in Drosophila , in intestinal stem cell maintenance and suppressor of differentiation.