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Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis

The Drosophila testis is a well-established system for studying stem cell self-renewal and competition. In this tissue, the niche supports two stem cell populations, germ line stem cells (GSCs), which give rise to sperm, and somatic stem cells called cyst stem cells (CySCs), which support GSCs and t...

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Autores principales: Amoyel, Marc, Anderson, Jason, Suisse, Annabelle, Glasner, Johanna, Bach, Erika A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4726490/
https://www.ncbi.nlm.nih.gov/pubmed/26807580
http://dx.doi.org/10.1371/journal.pgen.1005815
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author Amoyel, Marc
Anderson, Jason
Suisse, Annabelle
Glasner, Johanna
Bach, Erika A.
author_facet Amoyel, Marc
Anderson, Jason
Suisse, Annabelle
Glasner, Johanna
Bach, Erika A.
author_sort Amoyel, Marc
collection PubMed
description The Drosophila testis is a well-established system for studying stem cell self-renewal and competition. In this tissue, the niche supports two stem cell populations, germ line stem cells (GSCs), which give rise to sperm, and somatic stem cells called cyst stem cells (CySCs), which support GSCs and their descendants. It has been established that CySCs compete with each other and with GSCs for niche access, and mutations have been identified that confer increased competitiveness to CySCs, resulting in the mutant stem cell and its descendants outcompeting wild type resident stem cells. Socs36E, which encodes a negative feedback inhibitor of the JAK/STAT pathway, was the first identified regulator of niche competition. The competitive behavior of Socs36E mutant CySCs was attributed to increased JAK/STAT signaling. Here we show that competitive behavior of Socs36E mutant CySCs is due in large part to unbridled Mitogen-Activated Protein Kinase (MAPK) signaling. In Socs36E mutant clones, MAPK activity is elevated. Furthermore, we find that clonal upregulation of MAPK in CySCs leads to their outcompetition of wild type CySCs and of GSCs, recapitulating the Socs36E mutant phenotype. Indeed, when MAPK activity is removed from Socs36E mutant clones, they lose their competitiveness but maintain self-renewal, presumably due to increased JAK/STAT signaling in these cells. Consistently, loss of JAK/STAT activity in Socs36E mutant clones severely impairs their self-renewal. Thus, our results enable the genetic separation of two essential processes that occur in stem cells. While some niche signals specify the intrinsic property of self-renewal, which is absolutely required in all stem cells for niche residence, additional signals control the ability of stem cells to compete with their neighbors. Socs36E is node through which these processes are linked, demonstrating that negative feedback inhibition integrates multiple aspects of stem cell behavior.
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spelling pubmed-47264902016-02-03 Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis Amoyel, Marc Anderson, Jason Suisse, Annabelle Glasner, Johanna Bach, Erika A. PLoS Genet Research Article The Drosophila testis is a well-established system for studying stem cell self-renewal and competition. In this tissue, the niche supports two stem cell populations, germ line stem cells (GSCs), which give rise to sperm, and somatic stem cells called cyst stem cells (CySCs), which support GSCs and their descendants. It has been established that CySCs compete with each other and with GSCs for niche access, and mutations have been identified that confer increased competitiveness to CySCs, resulting in the mutant stem cell and its descendants outcompeting wild type resident stem cells. Socs36E, which encodes a negative feedback inhibitor of the JAK/STAT pathway, was the first identified regulator of niche competition. The competitive behavior of Socs36E mutant CySCs was attributed to increased JAK/STAT signaling. Here we show that competitive behavior of Socs36E mutant CySCs is due in large part to unbridled Mitogen-Activated Protein Kinase (MAPK) signaling. In Socs36E mutant clones, MAPK activity is elevated. Furthermore, we find that clonal upregulation of MAPK in CySCs leads to their outcompetition of wild type CySCs and of GSCs, recapitulating the Socs36E mutant phenotype. Indeed, when MAPK activity is removed from Socs36E mutant clones, they lose their competitiveness but maintain self-renewal, presumably due to increased JAK/STAT signaling in these cells. Consistently, loss of JAK/STAT activity in Socs36E mutant clones severely impairs their self-renewal. Thus, our results enable the genetic separation of two essential processes that occur in stem cells. While some niche signals specify the intrinsic property of self-renewal, which is absolutely required in all stem cells for niche residence, additional signals control the ability of stem cells to compete with their neighbors. Socs36E is node through which these processes are linked, demonstrating that negative feedback inhibition integrates multiple aspects of stem cell behavior. Public Library of Science 2016-01-25 /pmc/articles/PMC4726490/ /pubmed/26807580 http://dx.doi.org/10.1371/journal.pgen.1005815 Text en © 2016 Amoyel et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Amoyel, Marc
Anderson, Jason
Suisse, Annabelle
Glasner, Johanna
Bach, Erika A.
Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis
title Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis
title_full Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis
title_fullStr Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis
title_full_unstemmed Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis
title_short Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis
title_sort socs36e controls niche competition by repressing mapk signaling in the drosophila testis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4726490/
https://www.ncbi.nlm.nih.gov/pubmed/26807580
http://dx.doi.org/10.1371/journal.pgen.1005815
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