Simultaneous control of stemness and differentiation by the transcription factor Escargot in adult stem cells: How can we tease them apart?

Abstract

The homeostatic turnover of adult organs and their regenerative capacity following injury depend on a careful balance between stem cell self-renewal (to maintain or enlarge the stem cell pool) and differentiation (to replace lost tissue). We have recently characterized the role of the Drosophila Snail family transcription factor escargot (esg) in testis cyst stem cells (CySCs) 1,2 and intestinal stem cells (ISCs). 3,4CySCs mutant for esg are not maintained as stem cells, but they remain capable of differentiating normally along the cyst cell lineage. In contrast, esg mutant CySCs that give rise to a closely related lineage, the apical hub cells, cannot maintain hub cell identity. Similarly, Esg maintains stemness of ISCs while regulating the terminal differentiation of progenitor cells into absorptive enterocytes or secretory enteroendocrine cells. Therefore, our findings suggest that Esg may play a conserved and pivotal regulatory role in adult stem cells, controlling both their maintenance and terminal differentiation. Here we propose that this dual regulatory role is due to simultaneous control by Esg of overlapping genetic programs and discuss the exciting challenges and opportunities that lie ahead to explore the underlying mechanisms experimentally.

Escargot controls somatic stem cell maintenance through the attenuation of the insulin receptor pathway in Drosophila

“…CtBP has also been shown to be required for CySC maintenance ( Leatherman and Dinardo, 2008 ). It will be interesting to investigate whether Esg acts through CtBP to downregulate InR and what additional Esg-binding partners are important for the positive regulation of ImpL2 ( Loza-Coll and Jones, 2016 ). Moreover, given the fact that Esg putatively controls the expression of many other genes ( Tables S1 and S2 ), future studies will aim to address whether these genes are also important in regulating CySC behavior in an Esg-dependent manner.…”

Reduced Neuronal Transcription of Escargot, the Drosophila Gene Encoding a Snail-Type Transcription Factor, Promotes Longevity

“…These general characteristics, however, do not shed light on the exact genetic and metabolic pathways underlying the changes in life span. In recent years, significant attention has been drawn to the fact that esg is expressed in stem cells in several tissues, including intestinal stem cells (ISCs), cyst stem cells and male germline stem cells and is a primary component of testis stem cells (Loza-Coll et al, 2014 ; Voog et al, 2014 ; Loza-Coll and Jones, 2016 ). The gastrointestinal tract of multicellular animals was recently recognized as an organ critically important for the control of homeostasis, life span, and aging (Jasper, 2015 ).…”

Distinct role of autophagy on angiogenesis: highlights on the effect of autophagy in endothelial lineage and progenitor cells

“…Compare to ESCs, ASCs, but not all types such as intestine crypt stem cells, pose a limited stemness feature which is localized in specific mature sites to repair tissues in response to certain diseases [ 26 , 27 ]. Maintenance of balance between stemness and differentiation in SCs is a very important issue [ 28 ]. An excessive differentiation rate may lead to cell aging, while untamed cell proliferation can raise the emergence of cancer cells formation [ 29 ].…”