Transcriptomic analysis of skeletal muscle regeneration across mouse lifespan identifies altered stem cell states
In aging, skeletal muscle regeneration declines due to alterations in both myogenic and non-myogenic cells and their interactions. This regenerative dysfunction is not understood comprehensively or with high spatiotemporal resolution. We collected an integrated atlas of 273,923 single-cell transcrip...
Gespeichert in:
| Veröffentlicht in: | Nature aging 2024-12, Vol.4 (12), p.1862-1881 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1881 |
|---|---|
| container_issue | 12 |
| container_start_page | 1862 |
| container_title | Nature aging |
| container_volume | 4 |
| creator | Walter, Lauren D. Orton, Jessica L. Ntekas, Ioannis Fong, Ern Hwei Hannah Maymi, Viviana I. Rudd, Brian D. De Vlaminck, Iwijn Elisseeff, Jennifer H. Cosgrove, Benjamin D. |
| description | In aging, skeletal muscle regeneration declines due to alterations in both myogenic and non-myogenic cells and their interactions. This regenerative dysfunction is not understood comprehensively or with high spatiotemporal resolution. We collected an integrated atlas of 273,923 single-cell transcriptomes and high-resolution spatial transcriptomic maps from muscles of young, old and geriatric mice (~5, 20 and 26 months old) at multiple time points following myotoxin injury. We identified eight immune cell types that displayed accelerated or delayed dynamics by age. We observed muscle stem cell states and trajectories specific to old and geriatric muscles and evaluated their association with senescence by scoring experimentally derived and curated gene signatures in both single-cell and spatial transcriptomic data. This revealed an elevation of senescent-like muscle stem cell subsets within injury zones uniquely in aged muscles. This Resource provides a holistic portrait of the altered cellular states underlying muscle regenerative decline across mouse lifespan.
Skeletal muscle regeneration declines during aging but the underlying processes are incompletely understood. Here the authors generated single-cell and spatial transcriptomics data from uninjured and injured muscles across mouse lifespan and observed age-specific immune cell dynamics and an elevation of senescent-like muscle stem cells in aged muscles. |
| doi_str_mv | 10.1038/s43587-024-00756-3 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11645289</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3144206339</sourcerecordid><originalsourceid>FETCH-LOGICAL-c312t-903176f0dad6b5e55c5a6eb2c680a82160c64a772c85774793a71a846abfb8323</originalsourceid><addsrcrecordid>eNp9kUtv1TAQhSMEolXpH2CBLLFhk-JH_LgrhCqgSJXYlLU1cSYXF8e59SRI_ff17S2lsGDlkebM8Zz5mua14GeCK_eeOqWdbbnsWs6tNq161hxLY2TrOqOfP6mPmlOia8651EJxI182R2qjrdPaHTc3VwUyhRJ3yzzFwCBDuqVIbB4Z_cSECyQ2rRQSsoJbzFhgiXNmEMpMxKZ5JWQpjkg7yCwOmJc4RiQGacGCA6MFJxYwpVrBgvSqeTFCIjx9eE-a758_XZ1ftJffvnw9_3jZBiXk0m64EtaMfIDB9Bq1DhoM9jIYx8FJYXgwHVgrg9PWdnajwAqoeaEfe6ekOmk-HHx3az_hEOpiBZLflThBufUzRP93J8cffjv_8kKYTku3qQ7vHhzKfLMiLX6KtE8CGWtsr4SSomKQvErf_iO9ntdSb7lXdZ3kRqm9oTyo7m9XcHzcRnC_p-oPVH2l6u-pelWH3jzN8Tjym2EVqIOAaitvsfz5-z-2d4d7r5Y</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3144206339</pqid></control><display><type>article</type><title>Transcriptomic analysis of skeletal muscle regeneration across mouse lifespan identifies altered stem cell states</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><source>Nature</source><creator>Walter, Lauren D. ; Orton, Jessica L. ; Ntekas, Ioannis ; Fong, Ern Hwei Hannah ; Maymi, Viviana I. ; Rudd, Brian D. ; De Vlaminck, Iwijn ; Elisseeff, Jennifer H. ; Cosgrove, Benjamin D.</creator><creatorcontrib>Walter, Lauren D. ; Orton, Jessica L. ; Ntekas, Ioannis ; Fong, Ern Hwei Hannah ; Maymi, Viviana I. ; Rudd, Brian D. ; De Vlaminck, Iwijn ; Elisseeff, Jennifer H. ; Cosgrove, Benjamin D.</creatorcontrib><description>In aging, skeletal muscle regeneration declines due to alterations in both myogenic and non-myogenic cells and their interactions. This regenerative dysfunction is not understood comprehensively or with high spatiotemporal resolution. We collected an integrated atlas of 273,923 single-cell transcriptomes and high-resolution spatial transcriptomic maps from muscles of young, old and geriatric mice (~5, 20 and 26 months old) at multiple time points following myotoxin injury. We identified eight immune cell types that displayed accelerated or delayed dynamics by age. We observed muscle stem cell states and trajectories specific to old and geriatric muscles and evaluated their association with senescence by scoring experimentally derived and curated gene signatures in both single-cell and spatial transcriptomic data. This revealed an elevation of senescent-like muscle stem cell subsets within injury zones uniquely in aged muscles. This Resource provides a holistic portrait of the altered cellular states underlying muscle regenerative decline across mouse lifespan.
Skeletal muscle regeneration declines during aging but the underlying processes are incompletely understood. Here the authors generated single-cell and spatial transcriptomics data from uninjured and injured muscles across mouse lifespan and observed age-specific immune cell dynamics and an elevation of senescent-like muscle stem cells in aged muscles.</description><identifier>ISSN: 2662-8465</identifier><identifier>EISSN: 2662-8465</identifier><identifier>DOI: 10.1038/s43587-024-00756-3</identifier><identifier>PMID: 39578558</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>13/100 ; 13/51 ; 45/100 ; 45/91 ; 631/114/2164 ; 631/532/7 ; 64/60 ; Aging - genetics ; Aging - physiology ; Animals ; Biomedical and Life Sciences ; Gene Expression Profiling ; Geriatrics ; Life Sciences ; Longevity - genetics ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal - metabolism ; Muscle, Skeletal - physiology ; Musculoskeletal system ; Regeneration - genetics ; Resource ; Single-Cell Analysis ; Stem cells ; Stem Cells - cytology ; Stem Cells - metabolism ; Transcriptome</subject><ispartof>Nature aging, 2024-12, Vol.4 (12), p.1862-1881</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>Copyright Nature Publishing Group Dec 2024</rights><rights>The Author(s) 2024 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c312t-903176f0dad6b5e55c5a6eb2c680a82160c64a772c85774793a71a846abfb8323</cites><orcidid>0000-0003-2164-350X ; 0000-0002-4157-1665 ; 0000-0002-1575-3510 ; 0000-0002-5066-1996 ; 0000-0001-6085-7311 ; 0000-0001-7445-8207 ; 0000-0002-9742-8358</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s43587-024-00756-3$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s43587-024-00756-3$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39578558$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Walter, Lauren D.</creatorcontrib><creatorcontrib>Orton, Jessica L.</creatorcontrib><creatorcontrib>Ntekas, Ioannis</creatorcontrib><creatorcontrib>Fong, Ern Hwei Hannah</creatorcontrib><creatorcontrib>Maymi, Viviana I.</creatorcontrib><creatorcontrib>Rudd, Brian D.</creatorcontrib><creatorcontrib>De Vlaminck, Iwijn</creatorcontrib><creatorcontrib>Elisseeff, Jennifer H.</creatorcontrib><creatorcontrib>Cosgrove, Benjamin D.</creatorcontrib><title>Transcriptomic analysis of skeletal muscle regeneration across mouse lifespan identifies altered stem cell states</title><title>Nature aging</title><addtitle>Nat Aging</addtitle><addtitle>Nat Aging</addtitle><description>In aging, skeletal muscle regeneration declines due to alterations in both myogenic and non-myogenic cells and their interactions. This regenerative dysfunction is not understood comprehensively or with high spatiotemporal resolution. We collected an integrated atlas of 273,923 single-cell transcriptomes and high-resolution spatial transcriptomic maps from muscles of young, old and geriatric mice (~5, 20 and 26 months old) at multiple time points following myotoxin injury. We identified eight immune cell types that displayed accelerated or delayed dynamics by age. We observed muscle stem cell states and trajectories specific to old and geriatric muscles and evaluated their association with senescence by scoring experimentally derived and curated gene signatures in both single-cell and spatial transcriptomic data. This revealed an elevation of senescent-like muscle stem cell subsets within injury zones uniquely in aged muscles. This Resource provides a holistic portrait of the altered cellular states underlying muscle regenerative decline across mouse lifespan.
Skeletal muscle regeneration declines during aging but the underlying processes are incompletely understood. Here the authors generated single-cell and spatial transcriptomics data from uninjured and injured muscles across mouse lifespan and observed age-specific immune cell dynamics and an elevation of senescent-like muscle stem cells in aged muscles.</description><subject>13/100</subject><subject>13/51</subject><subject>45/100</subject><subject>45/91</subject><subject>631/114/2164</subject><subject>631/532/7</subject><subject>64/60</subject><subject>Aging - genetics</subject><subject>Aging - physiology</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Gene Expression Profiling</subject><subject>Geriatrics</subject><subject>Life Sciences</subject><subject>Longevity - genetics</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscle, Skeletal - physiology</subject><subject>Musculoskeletal system</subject><subject>Regeneration - genetics</subject><subject>Resource</subject><subject>Single-Cell Analysis</subject><subject>Stem cells</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - metabolism</subject><subject>Transcriptome</subject><issn>2662-8465</issn><issn>2662-8465</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kUtv1TAQhSMEolXpH2CBLLFhk-JH_LgrhCqgSJXYlLU1cSYXF8e59SRI_ff17S2lsGDlkebM8Zz5mua14GeCK_eeOqWdbbnsWs6tNq161hxLY2TrOqOfP6mPmlOia8651EJxI182R2qjrdPaHTc3VwUyhRJ3yzzFwCBDuqVIbB4Z_cSECyQ2rRQSsoJbzFhgiXNmEMpMxKZ5JWQpjkg7yCwOmJc4RiQGacGCA6MFJxYwpVrBgvSqeTFCIjx9eE-a758_XZ1ftJffvnw9_3jZBiXk0m64EtaMfIDB9Bq1DhoM9jIYx8FJYXgwHVgrg9PWdnajwAqoeaEfe6ekOmk-HHx3az_hEOpiBZLflThBufUzRP93J8cffjv_8kKYTku3qQ7vHhzKfLMiLX6KtE8CGWtsr4SSomKQvErf_iO9ntdSb7lXdZ3kRqm9oTyo7m9XcHzcRnC_p-oPVH2l6u-pelWH3jzN8Tjym2EVqIOAaitvsfz5-z-2d4d7r5Y</recordid><startdate>20241201</startdate><enddate>20241201</enddate><creator>Walter, Lauren D.</creator><creator>Orton, Jessica L.</creator><creator>Ntekas, Ioannis</creator><creator>Fong, Ern Hwei Hannah</creator><creator>Maymi, Viviana I.</creator><creator>Rudd, Brian D.</creator><creator>De Vlaminck, Iwijn</creator><creator>Elisseeff, Jennifer H.</creator><creator>Cosgrove, Benjamin D.</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2164-350X</orcidid><orcidid>https://orcid.org/0000-0002-4157-1665</orcidid><orcidid>https://orcid.org/0000-0002-1575-3510</orcidid><orcidid>https://orcid.org/0000-0002-5066-1996</orcidid><orcidid>https://orcid.org/0000-0001-6085-7311</orcidid><orcidid>https://orcid.org/0000-0001-7445-8207</orcidid><orcidid>https://orcid.org/0000-0002-9742-8358</orcidid></search><sort><creationdate>20241201</creationdate><title>Transcriptomic analysis of skeletal muscle regeneration across mouse lifespan identifies altered stem cell states</title><author>Walter, Lauren D. ; Orton, Jessica L. ; Ntekas, Ioannis ; Fong, Ern Hwei Hannah ; Maymi, Viviana I. ; Rudd, Brian D. ; De Vlaminck, Iwijn ; Elisseeff, Jennifer H. ; Cosgrove, Benjamin D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c312t-903176f0dad6b5e55c5a6eb2c680a82160c64a772c85774793a71a846abfb8323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>13/100</topic><topic>13/51</topic><topic>45/100</topic><topic>45/91</topic><topic>631/114/2164</topic><topic>631/532/7</topic><topic>64/60</topic><topic>Aging - genetics</topic><topic>Aging - physiology</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Gene Expression Profiling</topic><topic>Geriatrics</topic><topic>Life Sciences</topic><topic>Longevity - genetics</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscle, Skeletal - physiology</topic><topic>Musculoskeletal system</topic><topic>Regeneration - genetics</topic><topic>Resource</topic><topic>Single-Cell Analysis</topic><topic>Stem cells</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - metabolism</topic><topic>Transcriptome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Walter, Lauren D.</creatorcontrib><creatorcontrib>Orton, Jessica L.</creatorcontrib><creatorcontrib>Ntekas, Ioannis</creatorcontrib><creatorcontrib>Fong, Ern Hwei Hannah</creatorcontrib><creatorcontrib>Maymi, Viviana I.</creatorcontrib><creatorcontrib>Rudd, Brian D.</creatorcontrib><creatorcontrib>De Vlaminck, Iwijn</creatorcontrib><creatorcontrib>Elisseeff, Jennifer H.</creatorcontrib><creatorcontrib>Cosgrove, Benjamin D.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature aging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Walter, Lauren D.</au><au>Orton, Jessica L.</au><au>Ntekas, Ioannis</au><au>Fong, Ern Hwei Hannah</au><au>Maymi, Viviana I.</au><au>Rudd, Brian D.</au><au>De Vlaminck, Iwijn</au><au>Elisseeff, Jennifer H.</au><au>Cosgrove, Benjamin D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcriptomic analysis of skeletal muscle regeneration across mouse lifespan identifies altered stem cell states</atitle><jtitle>Nature aging</jtitle><stitle>Nat Aging</stitle><addtitle>Nat Aging</addtitle><date>2024-12-01</date><risdate>2024</risdate><volume>4</volume><issue>12</issue><spage>1862</spage><epage>1881</epage><pages>1862-1881</pages><issn>2662-8465</issn><eissn>2662-8465</eissn><abstract>In aging, skeletal muscle regeneration declines due to alterations in both myogenic and non-myogenic cells and their interactions. This regenerative dysfunction is not understood comprehensively or with high spatiotemporal resolution. We collected an integrated atlas of 273,923 single-cell transcriptomes and high-resolution spatial transcriptomic maps from muscles of young, old and geriatric mice (~5, 20 and 26 months old) at multiple time points following myotoxin injury. We identified eight immune cell types that displayed accelerated or delayed dynamics by age. We observed muscle stem cell states and trajectories specific to old and geriatric muscles and evaluated their association with senescence by scoring experimentally derived and curated gene signatures in both single-cell and spatial transcriptomic data. This revealed an elevation of senescent-like muscle stem cell subsets within injury zones uniquely in aged muscles. This Resource provides a holistic portrait of the altered cellular states underlying muscle regenerative decline across mouse lifespan.
Skeletal muscle regeneration declines during aging but the underlying processes are incompletely understood. Here the authors generated single-cell and spatial transcriptomics data from uninjured and injured muscles across mouse lifespan and observed age-specific immune cell dynamics and an elevation of senescent-like muscle stem cells in aged muscles.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>39578558</pmid><doi>10.1038/s43587-024-00756-3</doi><tpages>20</tpages><orcidid>https://orcid.org/0000-0003-2164-350X</orcidid><orcidid>https://orcid.org/0000-0002-4157-1665</orcidid><orcidid>https://orcid.org/0000-0002-1575-3510</orcidid><orcidid>https://orcid.org/0000-0002-5066-1996</orcidid><orcidid>https://orcid.org/0000-0001-6085-7311</orcidid><orcidid>https://orcid.org/0000-0001-7445-8207</orcidid><orcidid>https://orcid.org/0000-0002-9742-8358</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2662-8465 |
| ispartof | Nature aging, 2024-12, Vol.4 (12), p.1862-1881 |
| issn | 2662-8465 2662-8465 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11645289 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature |
| subjects | 13/100 13/51 45/100 45/91 631/114/2164 631/532/7 64/60 Aging - genetics Aging - physiology Animals Biomedical and Life Sciences Gene Expression Profiling Geriatrics Life Sciences Longevity - genetics Mice Mice, Inbred C57BL Muscle, Skeletal - metabolism Muscle, Skeletal - physiology Musculoskeletal system Regeneration - genetics Resource Single-Cell Analysis Stem cells Stem Cells - cytology Stem Cells - metabolism Transcriptome |
| title | Transcriptomic analysis of skeletal muscle regeneration across mouse lifespan identifies altered stem cell states |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T16%3A00%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Transcriptomic%20analysis%20of%20skeletal%20muscle%20regeneration%20across%20mouse%20lifespan%20identifies%20altered%20stem%20cell%20states&rft.jtitle=Nature%20aging&rft.au=Walter,%20Lauren%20D.&rft.date=2024-12-01&rft.volume=4&rft.issue=12&rft.spage=1862&rft.epage=1881&rft.pages=1862-1881&rft.issn=2662-8465&rft.eissn=2662-8465&rft_id=info:doi/10.1038/s43587-024-00756-3&rft_dat=%3Cproquest_pubme%3E3144206339%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3144206339&rft_id=info:pmid/39578558&rfr_iscdi=true |