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A single-cell atlas of bovine skeletal muscle reveals mechanisms regulating intramuscular adipogenesis and fibrogenesis
Intramuscular fat (IMF) and intramuscular connective tissue (IMC) are often seen in human myopathies and are central to beef quality. The mechanisms regulating their accumulation remain poorly understood. Here, we explored the possibility of using beef cattle as a novel model for mechanistic studies...
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| Published in: | Journal of cachexia, sarcopenia and muscle sarcopenia and muscle, 2023-10, Vol.14 (5), p.2152-2167 |
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| container_title | Journal of cachexia, sarcopenia and muscle |
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| creator | Wang, Leshan Gao, Peidong Li, Chaoyang Liu, Qianglin Yao, Zeyang Li, Yuxia Zhang, Xujia Sun, Jiangwen Simintiras, Constantine Welborn, Matthew McMillin, Kenneth Oprescu, Stephanie Kuang, Shihuan Fu, Xing |
| description | Intramuscular fat (IMF) and intramuscular connective tissue (IMC) are often seen in human myopathies and are central to beef quality. The mechanisms regulating their accumulation remain poorly understood. Here, we explored the possibility of using beef cattle as a novel model for mechanistic studies of intramuscular adipogenesis and fibrogenesis.
Skeletal muscle single-cell RNAseq was performed on three cattle breeds, including Wagyu (high IMF), Brahman (abundant IMC but scarce IMF), and Wagyu/Brahman cross. Sophisticated bioinformatics analyses, including clustering analysis, gene set enrichment analyses, gene regulatory network construction, RNA velocity, pseudotime analysis, and cell-cell communication analysis, were performed to elucidate heterogeneities and differentiation processes of individual cell types and differences between cattle breeds. Experiments were conducted to validate the function and specificity of identified key regulatory and marker genes. Integrated analysis with multiple published human and non-human primate datasets was performed to identify common mechanisms.
A total of 32 708 cells and 21 clusters were identified, including fibro/adipogenic progenitor (FAP) and other resident and infiltrating cell types. We identified an endomysial adipogenic FAP subpopulation enriched for COL4A1 and CFD (log2FC = 3.19 and 1.92, respectively; P |
| doi_str_mv | 10.1002/jcsm.13292 |
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| fullrecord | <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_e77cbf1d0fc54af0a6bb0da511022bf8</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_e77cbf1d0fc54af0a6bb0da511022bf8</doaj_id><sourcerecordid>2836879062</sourcerecordid><originalsourceid>FETCH-LOGICAL-c473t-85792406b506f67ba7b0c7b6a35dfc56db609d895d7877a50c51bdc48b2c0a6c3</originalsourceid><addsrcrecordid>eNpdkk1v1DAQhiMEolXphR-ALHFBlVLGSWzHJ1RVFCpV4gJna_yRrRcnXuxkEf8ep7utKL7Yev340Yw1VfWWwiUFaD5uTR4vadvI5kV12lAJNQeQL49nJiU9qc5z3kJZHaecwevqpBVdK6EVp9XvK5L9tAmuNi4EgnPATOJAdNz7yZH80wU3YyDjkk1wJLm9w5DJ6Mw9Tj6PuUSbJeBcJMRPc8KVLEEiaP0ubtzkss8EJ0sGr9Nj8KZ6NRSROz_uZ9WPm8_fr7_Wd9--3F5f3dWmE-1c90zIpgOuGfCBC41CgxGaY8vsYBi3moO0vWRW9EIgA8OotqbrdWMAuWnPqtuD10bcql3yI6Y_KqJXD0FMG4Vp9qU35YQweqAWirjDoTzXGiwySqFp9NAX16eDa7fo0Vnj1nbDM-nzm8nfq03cKwpMAPSiGD4cDSn-Wlye1ejz-vE4ubhk1fQt74UE3hT0_X_oNi5pKn9VKMFpx4Sghbo4UCbFnJMbnqqhoNb5UOt8qIf5KPC7f-t_Qh-nof0LMDy5Mw</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2876145771</pqid></control><display><type>article</type><title>A single-cell atlas of bovine skeletal muscle reveals mechanisms regulating intramuscular adipogenesis and fibrogenesis</title><source>Open Access: Wiley-Blackwell Open Access Journals</source><source>Publicly Available Content (ProQuest)</source><source>PubMed Central</source><creator>Wang, Leshan ; Gao, Peidong ; Li, Chaoyang ; Liu, Qianglin ; Yao, Zeyang ; Li, Yuxia ; Zhang, Xujia ; Sun, Jiangwen ; Simintiras, Constantine ; Welborn, Matthew ; McMillin, Kenneth ; Oprescu, Stephanie ; Kuang, Shihuan ; Fu, Xing</creator><creatorcontrib>Wang, Leshan ; Gao, Peidong ; Li, Chaoyang ; Liu, Qianglin ; Yao, Zeyang ; Li, Yuxia ; Zhang, Xujia ; Sun, Jiangwen ; Simintiras, Constantine ; Welborn, Matthew ; McMillin, Kenneth ; Oprescu, Stephanie ; Kuang, Shihuan ; Fu, Xing</creatorcontrib><description><![CDATA[Intramuscular fat (IMF) and intramuscular connective tissue (IMC) are often seen in human myopathies and are central to beef quality. The mechanisms regulating their accumulation remain poorly understood. Here, we explored the possibility of using beef cattle as a novel model for mechanistic studies of intramuscular adipogenesis and fibrogenesis.
Skeletal muscle single-cell RNAseq was performed on three cattle breeds, including Wagyu (high IMF), Brahman (abundant IMC but scarce IMF), and Wagyu/Brahman cross. Sophisticated bioinformatics analyses, including clustering analysis, gene set enrichment analyses, gene regulatory network construction, RNA velocity, pseudotime analysis, and cell-cell communication analysis, were performed to elucidate heterogeneities and differentiation processes of individual cell types and differences between cattle breeds. Experiments were conducted to validate the function and specificity of identified key regulatory and marker genes. Integrated analysis with multiple published human and non-human primate datasets was performed to identify common mechanisms.
A total of 32 708 cells and 21 clusters were identified, including fibro/adipogenic progenitor (FAP) and other resident and infiltrating cell types. We identified an endomysial adipogenic FAP subpopulation enriched for COL4A1 and CFD (log2FC = 3.19 and 1.92, respectively; P < 0.0001) and a perimysial fibrogenic FAP subpopulation enriched for COL1A1 and POSTN (log2FC = 1.83 and 0.87, respectively; P < 0.0001), both of which were likely derived from an unspecified subpopulation. Further analysis revealed more progressed adipogenic programming of Wagyu FAPs and more advanced fibrogenic programming of Brahman FAPs. Mechanistically, NAB2 drives CFD expression, which in turn promotes adipogenesis. CFD expression in FAPs of young cattle before the onset of intramuscular adipogenesis was predictive of IMF contents in adulthood (R
= 0.885, P < 0.01). Similar adipogenic and fibrogenic FAPs were identified in humans and monkeys. In aged humans with metabolic syndrome and progressed Duchenne muscular dystrophy (DMD) patients, increased CFD expression was observed (P < 0.05 and P < 0.0001, respectively), which was positively correlated with adipogenic marker expression, including ADIPOQ (R
= 0.303, P < 0.01; and R
= 0.348, P < 0.01, respectively). The specificity of Postn/POSTN as a fibrogenic FAP marker was validated using a lineage-tracing mouse line. POSTN expression was elevated in Brahman FAPs (P < 0.0001) and DMD patients (P < 0.01) but not in aged humans. Strong interactions between vascular cells and FAPs were also identified.
Our study demonstrates the feasibility of beef cattle as a model for studying IMF and IMC. We illustrate the FAP programming during intramuscular adipogenesis and fibrogenesis and reveal the reliability of CFD as a predictor and biomarker of IMF accumulation in cattle and humans.]]></description><identifier>ISSN: 2190-5991</identifier><identifier>EISSN: 2190-6009</identifier><identifier>DOI: 10.1002/jcsm.13292</identifier><identifier>PMID: 37439037</identifier><language>eng</language><publisher>Germany: John Wiley & Sons, Inc</publisher><subject>Adipogenesis ; Adipogenesis - physiology ; Aged ; Animals ; Beef cattle ; Blood vessels ; Cattle ; Cell Differentiation ; Cells ; Communication ; Comparative analysis ; Datasets ; Fibro/adipogenic progenitor ; Fibrogenesis ; Gene expression ; Genomics ; Humans ; Intramuscular adipose tissue ; Mice ; Muscle, Skeletal - metabolism ; Muscular Dystrophy, Duchenne ; Musculoskeletal system ; Original ; Reproducibility of Results ; Single‐cell RNAseq ; Smooth muscle</subject><ispartof>Journal of cachexia, sarcopenia and muscle, 2023-10, Vol.14 (5), p.2152-2167</ispartof><rights>2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.</rights><rights>2023. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c473t-85792406b506f67ba7b0c7b6a35dfc56db609d895d7877a50c51bdc48b2c0a6c3</citedby><cites>FETCH-LOGICAL-c473t-85792406b506f67ba7b0c7b6a35dfc56db609d895d7877a50c51bdc48b2c0a6c3</cites><orcidid>0000-0001-5419-2691</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2876145771/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2876145771?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25732,27903,27904,36991,36992,44569,53770,53772,74873</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37439037$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Leshan</creatorcontrib><creatorcontrib>Gao, Peidong</creatorcontrib><creatorcontrib>Li, Chaoyang</creatorcontrib><creatorcontrib>Liu, Qianglin</creatorcontrib><creatorcontrib>Yao, Zeyang</creatorcontrib><creatorcontrib>Li, Yuxia</creatorcontrib><creatorcontrib>Zhang, Xujia</creatorcontrib><creatorcontrib>Sun, Jiangwen</creatorcontrib><creatorcontrib>Simintiras, Constantine</creatorcontrib><creatorcontrib>Welborn, Matthew</creatorcontrib><creatorcontrib>McMillin, Kenneth</creatorcontrib><creatorcontrib>Oprescu, Stephanie</creatorcontrib><creatorcontrib>Kuang, Shihuan</creatorcontrib><creatorcontrib>Fu, Xing</creatorcontrib><title>A single-cell atlas of bovine skeletal muscle reveals mechanisms regulating intramuscular adipogenesis and fibrogenesis</title><title>Journal of cachexia, sarcopenia and muscle</title><addtitle>J Cachexia Sarcopenia Muscle</addtitle><description><![CDATA[Intramuscular fat (IMF) and intramuscular connective tissue (IMC) are often seen in human myopathies and are central to beef quality. The mechanisms regulating their accumulation remain poorly understood. Here, we explored the possibility of using beef cattle as a novel model for mechanistic studies of intramuscular adipogenesis and fibrogenesis.
Skeletal muscle single-cell RNAseq was performed on three cattle breeds, including Wagyu (high IMF), Brahman (abundant IMC but scarce IMF), and Wagyu/Brahman cross. Sophisticated bioinformatics analyses, including clustering analysis, gene set enrichment analyses, gene regulatory network construction, RNA velocity, pseudotime analysis, and cell-cell communication analysis, were performed to elucidate heterogeneities and differentiation processes of individual cell types and differences between cattle breeds. Experiments were conducted to validate the function and specificity of identified key regulatory and marker genes. Integrated analysis with multiple published human and non-human primate datasets was performed to identify common mechanisms.
A total of 32 708 cells and 21 clusters were identified, including fibro/adipogenic progenitor (FAP) and other resident and infiltrating cell types. We identified an endomysial adipogenic FAP subpopulation enriched for COL4A1 and CFD (log2FC = 3.19 and 1.92, respectively; P < 0.0001) and a perimysial fibrogenic FAP subpopulation enriched for COL1A1 and POSTN (log2FC = 1.83 and 0.87, respectively; P < 0.0001), both of which were likely derived from an unspecified subpopulation. Further analysis revealed more progressed adipogenic programming of Wagyu FAPs and more advanced fibrogenic programming of Brahman FAPs. Mechanistically, NAB2 drives CFD expression, which in turn promotes adipogenesis. CFD expression in FAPs of young cattle before the onset of intramuscular adipogenesis was predictive of IMF contents in adulthood (R
= 0.885, P < 0.01). Similar adipogenic and fibrogenic FAPs were identified in humans and monkeys. In aged humans with metabolic syndrome and progressed Duchenne muscular dystrophy (DMD) patients, increased CFD expression was observed (P < 0.05 and P < 0.0001, respectively), which was positively correlated with adipogenic marker expression, including ADIPOQ (R
= 0.303, P < 0.01; and R
= 0.348, P < 0.01, respectively). The specificity of Postn/POSTN as a fibrogenic FAP marker was validated using a lineage-tracing mouse line. POSTN expression was elevated in Brahman FAPs (P < 0.0001) and DMD patients (P < 0.01) but not in aged humans. Strong interactions between vascular cells and FAPs were also identified.
Our study demonstrates the feasibility of beef cattle as a model for studying IMF and IMC. We illustrate the FAP programming during intramuscular adipogenesis and fibrogenesis and reveal the reliability of CFD as a predictor and biomarker of IMF accumulation in cattle and humans.]]></description><subject>Adipogenesis</subject><subject>Adipogenesis - physiology</subject><subject>Aged</subject><subject>Animals</subject><subject>Beef cattle</subject><subject>Blood vessels</subject><subject>Cattle</subject><subject>Cell Differentiation</subject><subject>Cells</subject><subject>Communication</subject><subject>Comparative analysis</subject><subject>Datasets</subject><subject>Fibro/adipogenic progenitor</subject><subject>Fibrogenesis</subject><subject>Gene expression</subject><subject>Genomics</subject><subject>Humans</subject><subject>Intramuscular adipose tissue</subject><subject>Mice</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscular Dystrophy, Duchenne</subject><subject>Musculoskeletal system</subject><subject>Original</subject><subject>Reproducibility of Results</subject><subject>Single‐cell RNAseq</subject><subject>Smooth muscle</subject><issn>2190-5991</issn><issn>2190-6009</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdkk1v1DAQhiMEolXphR-ALHFBlVLGSWzHJ1RVFCpV4gJna_yRrRcnXuxkEf8ep7utKL7Yev340Yw1VfWWwiUFaD5uTR4vadvI5kV12lAJNQeQL49nJiU9qc5z3kJZHaecwevqpBVdK6EVp9XvK5L9tAmuNi4EgnPATOJAdNz7yZH80wU3YyDjkk1wJLm9w5DJ6Mw9Tj6PuUSbJeBcJMRPc8KVLEEiaP0ubtzkss8EJ0sGr9Nj8KZ6NRSROz_uZ9WPm8_fr7_Wd9--3F5f3dWmE-1c90zIpgOuGfCBC41CgxGaY8vsYBi3moO0vWRW9EIgA8OotqbrdWMAuWnPqtuD10bcql3yI6Y_KqJXD0FMG4Vp9qU35YQweqAWirjDoTzXGiwySqFp9NAX16eDa7fo0Vnj1nbDM-nzm8nfq03cKwpMAPSiGD4cDSn-Wlye1ejz-vE4ubhk1fQt74UE3hT0_X_oNi5pKn9VKMFpx4Sghbo4UCbFnJMbnqqhoNb5UOt8qIf5KPC7f-t_Qh-nof0LMDy5Mw</recordid><startdate>20231001</startdate><enddate>20231001</enddate><creator>Wang, Leshan</creator><creator>Gao, Peidong</creator><creator>Li, Chaoyang</creator><creator>Liu, Qianglin</creator><creator>Yao, Zeyang</creator><creator>Li, Yuxia</creator><creator>Zhang, Xujia</creator><creator>Sun, Jiangwen</creator><creator>Simintiras, Constantine</creator><creator>Welborn, Matthew</creator><creator>McMillin, Kenneth</creator><creator>Oprescu, Stephanie</creator><creator>Kuang, Shihuan</creator><creator>Fu, Xing</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><general>Wiley</general><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-5419-2691</orcidid></search><sort><creationdate>20231001</creationdate><title>A single-cell atlas of bovine skeletal muscle reveals mechanisms regulating intramuscular adipogenesis and fibrogenesis</title><author>Wang, Leshan ; Gao, Peidong ; Li, Chaoyang ; Liu, Qianglin ; Yao, Zeyang ; Li, Yuxia ; Zhang, Xujia ; Sun, Jiangwen ; Simintiras, Constantine ; Welborn, Matthew ; McMillin, Kenneth ; Oprescu, Stephanie ; Kuang, Shihuan ; Fu, Xing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c473t-85792406b506f67ba7b0c7b6a35dfc56db609d895d7877a50c51bdc48b2c0a6c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Adipogenesis</topic><topic>Adipogenesis - physiology</topic><topic>Aged</topic><topic>Animals</topic><topic>Beef cattle</topic><topic>Blood vessels</topic><topic>Cattle</topic><topic>Cell Differentiation</topic><topic>Cells</topic><topic>Communication</topic><topic>Comparative analysis</topic><topic>Datasets</topic><topic>Fibro/adipogenic progenitor</topic><topic>Fibrogenesis</topic><topic>Gene expression</topic><topic>Genomics</topic><topic>Humans</topic><topic>Intramuscular adipose tissue</topic><topic>Mice</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscular Dystrophy, Duchenne</topic><topic>Musculoskeletal system</topic><topic>Original</topic><topic>Reproducibility of Results</topic><topic>Single‐cell RNAseq</topic><topic>Smooth muscle</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Leshan</creatorcontrib><creatorcontrib>Gao, Peidong</creatorcontrib><creatorcontrib>Li, Chaoyang</creatorcontrib><creatorcontrib>Liu, Qianglin</creatorcontrib><creatorcontrib>Yao, Zeyang</creatorcontrib><creatorcontrib>Li, Yuxia</creatorcontrib><creatorcontrib>Zhang, Xujia</creatorcontrib><creatorcontrib>Sun, Jiangwen</creatorcontrib><creatorcontrib>Simintiras, Constantine</creatorcontrib><creatorcontrib>Welborn, Matthew</creatorcontrib><creatorcontrib>McMillin, Kenneth</creatorcontrib><creatorcontrib>Oprescu, Stephanie</creatorcontrib><creatorcontrib>Kuang, Shihuan</creatorcontrib><creatorcontrib>Fu, Xing</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Journal of cachexia, sarcopenia and muscle</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Leshan</au><au>Gao, Peidong</au><au>Li, Chaoyang</au><au>Liu, Qianglin</au><au>Yao, Zeyang</au><au>Li, Yuxia</au><au>Zhang, Xujia</au><au>Sun, Jiangwen</au><au>Simintiras, Constantine</au><au>Welborn, Matthew</au><au>McMillin, Kenneth</au><au>Oprescu, Stephanie</au><au>Kuang, Shihuan</au><au>Fu, Xing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A single-cell atlas of bovine skeletal muscle reveals mechanisms regulating intramuscular adipogenesis and fibrogenesis</atitle><jtitle>Journal of cachexia, sarcopenia and muscle</jtitle><addtitle>J Cachexia Sarcopenia Muscle</addtitle><date>2023-10-01</date><risdate>2023</risdate><volume>14</volume><issue>5</issue><spage>2152</spage><epage>2167</epage><pages>2152-2167</pages><issn>2190-5991</issn><eissn>2190-6009</eissn><abstract><![CDATA[Intramuscular fat (IMF) and intramuscular connective tissue (IMC) are often seen in human myopathies and are central to beef quality. The mechanisms regulating their accumulation remain poorly understood. Here, we explored the possibility of using beef cattle as a novel model for mechanistic studies of intramuscular adipogenesis and fibrogenesis.
Skeletal muscle single-cell RNAseq was performed on three cattle breeds, including Wagyu (high IMF), Brahman (abundant IMC but scarce IMF), and Wagyu/Brahman cross. Sophisticated bioinformatics analyses, including clustering analysis, gene set enrichment analyses, gene regulatory network construction, RNA velocity, pseudotime analysis, and cell-cell communication analysis, were performed to elucidate heterogeneities and differentiation processes of individual cell types and differences between cattle breeds. Experiments were conducted to validate the function and specificity of identified key regulatory and marker genes. Integrated analysis with multiple published human and non-human primate datasets was performed to identify common mechanisms.
A total of 32 708 cells and 21 clusters were identified, including fibro/adipogenic progenitor (FAP) and other resident and infiltrating cell types. We identified an endomysial adipogenic FAP subpopulation enriched for COL4A1 and CFD (log2FC = 3.19 and 1.92, respectively; P < 0.0001) and a perimysial fibrogenic FAP subpopulation enriched for COL1A1 and POSTN (log2FC = 1.83 and 0.87, respectively; P < 0.0001), both of which were likely derived from an unspecified subpopulation. Further analysis revealed more progressed adipogenic programming of Wagyu FAPs and more advanced fibrogenic programming of Brahman FAPs. Mechanistically, NAB2 drives CFD expression, which in turn promotes adipogenesis. CFD expression in FAPs of young cattle before the onset of intramuscular adipogenesis was predictive of IMF contents in adulthood (R
= 0.885, P < 0.01). Similar adipogenic and fibrogenic FAPs were identified in humans and monkeys. In aged humans with metabolic syndrome and progressed Duchenne muscular dystrophy (DMD) patients, increased CFD expression was observed (P < 0.05 and P < 0.0001, respectively), which was positively correlated with adipogenic marker expression, including ADIPOQ (R
= 0.303, P < 0.01; and R
= 0.348, P < 0.01, respectively). The specificity of Postn/POSTN as a fibrogenic FAP marker was validated using a lineage-tracing mouse line. POSTN expression was elevated in Brahman FAPs (P < 0.0001) and DMD patients (P < 0.01) but not in aged humans. Strong interactions between vascular cells and FAPs were also identified.
Our study demonstrates the feasibility of beef cattle as a model for studying IMF and IMC. We illustrate the FAP programming during intramuscular adipogenesis and fibrogenesis and reveal the reliability of CFD as a predictor and biomarker of IMF accumulation in cattle and humans.]]></abstract><cop>Germany</cop><pub>John Wiley & Sons, Inc</pub><pmid>37439037</pmid><doi>10.1002/jcsm.13292</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0001-5419-2691</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 2190-5991 |
| ispartof | Journal of cachexia, sarcopenia and muscle, 2023-10, Vol.14 (5), p.2152-2167 |
| issn | 2190-5991 2190-6009 |
| language | eng |
| recordid | cdi_doaj_primary_oai_doaj_org_article_e77cbf1d0fc54af0a6bb0da511022bf8 |
| source | Open Access: Wiley-Blackwell Open Access Journals; Publicly Available Content (ProQuest); PubMed Central |
| subjects | Adipogenesis Adipogenesis - physiology Aged Animals Beef cattle Blood vessels Cattle Cell Differentiation Cells Communication Comparative analysis Datasets Fibro/adipogenic progenitor Fibrogenesis Gene expression Genomics Humans Intramuscular adipose tissue Mice Muscle, Skeletal - metabolism Muscular Dystrophy, Duchenne Musculoskeletal system Original Reproducibility of Results Single‐cell RNAseq Smooth muscle |
| title | A single-cell atlas of bovine skeletal muscle reveals mechanisms regulating intramuscular adipogenesis and fibrogenesis |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-23T02%3A39%3A59IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20single-cell%20atlas%20of%20bovine%20skeletal%20muscle%20reveals%20mechanisms%20regulating%20intramuscular%20adipogenesis%20and%20fibrogenesis&rft.jtitle=Journal%20of%20cachexia,%20sarcopenia%20and%20muscle&rft.au=Wang,%20Leshan&rft.date=2023-10-01&rft.volume=14&rft.issue=5&rft.spage=2152&rft.epage=2167&rft.pages=2152-2167&rft.issn=2190-5991&rft.eissn=2190-6009&rft_id=info:doi/10.1002/jcsm.13292&rft_dat=%3Cproquest_doaj_%3E2836879062%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c473t-85792406b506f67ba7b0c7b6a35dfc56db609d895d7877a50c51bdc48b2c0a6c3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2876145771&rft_id=info:pmid/37439037&rfr_iscdi=true |