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The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts
BACKGROUND: Reversible cell cycle arrest (quiescence/G0) is characteristic of adult stem cells and is actively controlled at multiple levels. Quiescent cells also extend a primary cilium, which functions as a signaling hub. Primary cilia have been shown to be important in multiple developmental proc...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161131/ https://www.ncbi.nlm.nih.gov/pubmed/32293249 http://dx.doi.org/10.1186/s12860-020-00266-1 |
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author | Venugopal, Nisha Ghosh, Ananga Gala, Hardik Aloysius, Ajoy Vyas, Neha Dhawan, Jyotsna |
author_facet | Venugopal, Nisha Ghosh, Ananga Gala, Hardik Aloysius, Ajoy Vyas, Neha Dhawan, Jyotsna |
author_sort | Venugopal, Nisha |
collection | PubMed |
description | BACKGROUND: Reversible cell cycle arrest (quiescence/G0) is characteristic of adult stem cells and is actively controlled at multiple levels. Quiescent cells also extend a primary cilium, which functions as a signaling hub. Primary cilia have been shown to be important in multiple developmental processes, and are implicated in numerous developmental disorders. Although the association of the cilium with G0 is established, the role of the cilium in the control of the quiescence program is still poorly understood. RESULTS: Primary cilia are dynamically regulated across different states of cell cycle exit in skeletal muscle myoblasts: quiescent myoblasts elaborate a primary cilium in vivo and in vitro, but terminally differentiated myofibers do not. Myoblasts where ciliogenesis is ablated using RNAi against a key ciliary assembly protein (IFT88) can exit the cell cycle but display an altered quiescence program and impaired self-renewal. Specifically, the G0 transcriptome in IFT88 knockdown cells is aberrantly enriched for G2/M regulators, suggesting a focused repression of this network by the cilium. Cilium-ablated cells also exhibit features of activation including enhanced activity of Wnt and mitogen signaling and elevated protein synthesis via inactivation of the translational repressor 4E-BP1. CONCLUSIONS: Taken together, our results show that the primary cilium integrates and dampens proliferative signaling, represses translation and G2/M genes, and is integral to the establishment of the quiescence program. |
format | Online Article Text |
id | pubmed-7161131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-71611312020-04-22 The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts Venugopal, Nisha Ghosh, Ananga Gala, Hardik Aloysius, Ajoy Vyas, Neha Dhawan, Jyotsna BMC Mol Cell Biol Research Article BACKGROUND: Reversible cell cycle arrest (quiescence/G0) is characteristic of adult stem cells and is actively controlled at multiple levels. Quiescent cells also extend a primary cilium, which functions as a signaling hub. Primary cilia have been shown to be important in multiple developmental processes, and are implicated in numerous developmental disorders. Although the association of the cilium with G0 is established, the role of the cilium in the control of the quiescence program is still poorly understood. RESULTS: Primary cilia are dynamically regulated across different states of cell cycle exit in skeletal muscle myoblasts: quiescent myoblasts elaborate a primary cilium in vivo and in vitro, but terminally differentiated myofibers do not. Myoblasts where ciliogenesis is ablated using RNAi against a key ciliary assembly protein (IFT88) can exit the cell cycle but display an altered quiescence program and impaired self-renewal. Specifically, the G0 transcriptome in IFT88 knockdown cells is aberrantly enriched for G2/M regulators, suggesting a focused repression of this network by the cilium. Cilium-ablated cells also exhibit features of activation including enhanced activity of Wnt and mitogen signaling and elevated protein synthesis via inactivation of the translational repressor 4E-BP1. CONCLUSIONS: Taken together, our results show that the primary cilium integrates and dampens proliferative signaling, represses translation and G2/M genes, and is integral to the establishment of the quiescence program. BioMed Central 2020-04-15 /pmc/articles/PMC7161131/ /pubmed/32293249 http://dx.doi.org/10.1186/s12860-020-00266-1 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Venugopal, Nisha Ghosh, Ananga Gala, Hardik Aloysius, Ajoy Vyas, Neha Dhawan, Jyotsna The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts |
title | The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts |
title_full | The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts |
title_fullStr | The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts |
title_full_unstemmed | The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts |
title_short | The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts |
title_sort | primary cilium dampens proliferative signaling and represses a g2/m transcriptional network in quiescent myoblasts |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161131/ https://www.ncbi.nlm.nih.gov/pubmed/32293249 http://dx.doi.org/10.1186/s12860-020-00266-1 |
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