Cargando…
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...
Autores principales: | , , , , |
---|---|
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 |
_version_ | 1782411829173026816 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4726490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT amoyelmarc socs36econtrolsnichecompetitionbyrepressingmapksignalinginthedrosophilatestis AT andersonjason socs36econtrolsnichecompetitionbyrepressingmapksignalinginthedrosophilatestis AT suisseannabelle socs36econtrolsnichecompetitionbyrepressingmapksignalinginthedrosophilatestis AT glasnerjohanna socs36econtrolsnichecompetitionbyrepressingmapksignalinginthedrosophilatestis AT bacherikaa socs36econtrolsnichecompetitionbyrepressingmapksignalinginthedrosophilatestis |