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NG2-positive pericytes regulate homeostatic maintenance of slow-type skeletal muscle with rapid myonuclear turnover
BACKGROUND: Skeletal muscle comprises almost 40% of the human body and is essential for movement, structural support and metabolic homeostasis. Size of multinuclear skeletal muscle is stably maintained under steady conditions with the sporadic fusion of newly produced myocytes to compensate for the...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10433572/ https://www.ncbi.nlm.nih.gov/pubmed/37592340 http://dx.doi.org/10.1186/s13287-023-03433-1 |
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author | Tatsukawa, Takamitsu Kano, Kohei Nakajima, Kei-ichi Yazawa, Takashi Eguchi, Ryoji Kabara, Maki Horiuchi, Kiwamu Hayasaka, Taiki Matsuo, Risa Hasebe, Naoyuki Azuma, Nobuyoshi Kawabe, Jun-ichi |
author_facet | Tatsukawa, Takamitsu Kano, Kohei Nakajima, Kei-ichi Yazawa, Takashi Eguchi, Ryoji Kabara, Maki Horiuchi, Kiwamu Hayasaka, Taiki Matsuo, Risa Hasebe, Naoyuki Azuma, Nobuyoshi Kawabe, Jun-ichi |
author_sort | Tatsukawa, Takamitsu |
collection | PubMed |
description | BACKGROUND: Skeletal muscle comprises almost 40% of the human body and is essential for movement, structural support and metabolic homeostasis. Size of multinuclear skeletal muscle is stably maintained under steady conditions with the sporadic fusion of newly produced myocytes to compensate for the muscular turnover caused by daily wear and tear. It is becoming clear that microvascular pericytes (PCs) exhibit myogenic activity. However, whether PCs act as myogenic stem cells for the homeostatic maintenance of skeletal muscles during adulthood remains uncertain. METHODS: We utilized PC-fused myofibers using PC-specific lineage tracing mouse (NG2-CreERT/Rosa-tdTomato) to observe whether muscle resident PCs have myogenic potential during daily life. Genetic PC deletion mouse model (NG2-CreERT/DTA) was used to test whether PC differentiates to myofibers for maintenance of muscle structure and function under homeostatic condition. RESULTS: Under steady breeding conditions, tdTomato-expressing PCs were infused into myofibers, and subsequently, PC-derived nuclei were incorporated into myofibers. Especially in type-I slow-type myofibers such as the soleus, tdTomato(+) myofibers were already observed 3 days after PC labeling; their ratio reached a peak (approximately 80%) within 1 month and was maintained for more than 1 year. Consistently, the NG2(+) PC-specific deletion induced muscular atrophy in a slow-type myofiber-specific manner under steady breeding conditions. The number of myonucleus per volume of each myofiber was constant during observation period. CONCLUSIONS: These findings demonstrate that the turnover of myonuclei in slow-type myofibers is relatively fast, with PCs acting as myogenic stem cells—the suppliers of new myonuclei under steady conditions—and play a vital role in the homeostatic maintenance of slow-type muscles. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-023-03433-1. |
format | Online Article Text |
id | pubmed-10433572 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-104335722023-08-18 NG2-positive pericytes regulate homeostatic maintenance of slow-type skeletal muscle with rapid myonuclear turnover Tatsukawa, Takamitsu Kano, Kohei Nakajima, Kei-ichi Yazawa, Takashi Eguchi, Ryoji Kabara, Maki Horiuchi, Kiwamu Hayasaka, Taiki Matsuo, Risa Hasebe, Naoyuki Azuma, Nobuyoshi Kawabe, Jun-ichi Stem Cell Res Ther Research BACKGROUND: Skeletal muscle comprises almost 40% of the human body and is essential for movement, structural support and metabolic homeostasis. Size of multinuclear skeletal muscle is stably maintained under steady conditions with the sporadic fusion of newly produced myocytes to compensate for the muscular turnover caused by daily wear and tear. It is becoming clear that microvascular pericytes (PCs) exhibit myogenic activity. However, whether PCs act as myogenic stem cells for the homeostatic maintenance of skeletal muscles during adulthood remains uncertain. METHODS: We utilized PC-fused myofibers using PC-specific lineage tracing mouse (NG2-CreERT/Rosa-tdTomato) to observe whether muscle resident PCs have myogenic potential during daily life. Genetic PC deletion mouse model (NG2-CreERT/DTA) was used to test whether PC differentiates to myofibers for maintenance of muscle structure and function under homeostatic condition. RESULTS: Under steady breeding conditions, tdTomato-expressing PCs were infused into myofibers, and subsequently, PC-derived nuclei were incorporated into myofibers. Especially in type-I slow-type myofibers such as the soleus, tdTomato(+) myofibers were already observed 3 days after PC labeling; their ratio reached a peak (approximately 80%) within 1 month and was maintained for more than 1 year. Consistently, the NG2(+) PC-specific deletion induced muscular atrophy in a slow-type myofiber-specific manner under steady breeding conditions. The number of myonucleus per volume of each myofiber was constant during observation period. CONCLUSIONS: These findings demonstrate that the turnover of myonuclei in slow-type myofibers is relatively fast, with PCs acting as myogenic stem cells—the suppliers of new myonuclei under steady conditions—and play a vital role in the homeostatic maintenance of slow-type muscles. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-023-03433-1. BioMed Central 2023-08-17 /pmc/articles/PMC10433572/ /pubmed/37592340 http://dx.doi.org/10.1186/s13287-023-03433-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://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 Tatsukawa, Takamitsu Kano, Kohei Nakajima, Kei-ichi Yazawa, Takashi Eguchi, Ryoji Kabara, Maki Horiuchi, Kiwamu Hayasaka, Taiki Matsuo, Risa Hasebe, Naoyuki Azuma, Nobuyoshi Kawabe, Jun-ichi NG2-positive pericytes regulate homeostatic maintenance of slow-type skeletal muscle with rapid myonuclear turnover |
title | NG2-positive pericytes regulate homeostatic maintenance of slow-type skeletal muscle with rapid myonuclear turnover |
title_full | NG2-positive pericytes regulate homeostatic maintenance of slow-type skeletal muscle with rapid myonuclear turnover |
title_fullStr | NG2-positive pericytes regulate homeostatic maintenance of slow-type skeletal muscle with rapid myonuclear turnover |
title_full_unstemmed | NG2-positive pericytes regulate homeostatic maintenance of slow-type skeletal muscle with rapid myonuclear turnover |
title_short | NG2-positive pericytes regulate homeostatic maintenance of slow-type skeletal muscle with rapid myonuclear turnover |
title_sort | ng2-positive pericytes regulate homeostatic maintenance of slow-type skeletal muscle with rapid myonuclear turnover |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10433572/ https://www.ncbi.nlm.nih.gov/pubmed/37592340 http://dx.doi.org/10.1186/s13287-023-03433-1 |
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