Single-Nucleus RNA Sequencing Reveals Muscle-Region-Specific Differences in Fibro-Adipogenic Progenitors Driving Intramuscular Fat Accumulation
Background: Ectopic fat deposition refers to lipid accumulation that affects metabolic function and tissue characteristics. Japanese Black cattle are distinguished by their high intramuscular fat content, which contributes to their distinctive character. However, the genetic mechanisms underlying th...
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2025-03-01
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| author | Shuji Ueda Chiaki Kitamura Yuka Tateoka Akinori Kanai Yutaka Suzuki Itsuko Fukuda Yasuhito Shirai |
| author_facet | Shuji Ueda Chiaki Kitamura Yuka Tateoka Akinori Kanai Yutaka Suzuki Itsuko Fukuda Yasuhito Shirai |
| author_sort | Shuji Ueda |
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| description | Background: Ectopic fat deposition refers to lipid accumulation that affects metabolic function and tissue characteristics. Japanese Black cattle are distinguished by their high intramuscular fat content, which contributes to their distinctive character. However, the genetic mechanisms underlying these traits remain unclear. This study compared gene expression patterns in different muscle regions to identify genes associated with intramuscular fat accumulation. First, we conducted RNA sequencing to analyze differences in gene expression profiles among the sternocleidomastoid, pectoralis minor, and pectoralis major muscles. In addition, single-cell nuclear RNA sequencing was conducted to investigate the cellular composition of these muscle tissues. Results: Distinct gene expression patterns were observed among the different muscles. In the pectoralis, which contains a high proportion of intramuscular fat, adipocyte-related genes such as <i>FABP4</i>, <i>SCD</i>, and <i>ADIPOQ</i> were highly expressed. In addition, lipases such as <i>PNPLA2</i>, <i>LPL</i>, <i>MGLL</i>, and <i>LIPE</i> were predominantly expressed in intramuscular fat, whereas <i>PLA2G12A</i>, <i>PLD3</i>, and <i>ALOX15</i> were specifically expressed in myofibers. Moreover, a subclass of fibro–adipogenic progenitor cells that differentiate into intramuscular adipocytes was found to express genes related to microenvironment formation, including <i>ICAM1</i>, <i>TGFBRs</i>, and members of the <i>COL4A</i> family. Conclusions: This study provides novel insight into the genetic regulation of intramuscular fat accumulation. It improves our understanding of the molecular mechanisms underlying their distinctive meat characteristics. |
| format | Article |
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| language | English |
| publishDate | 2025-03-01 |
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| spelling | doaj-art-31b9989477384ff1bba53628ba3dd28f2025-08-20T02:18:14ZengMDPI AGMetabolites2218-19892025-03-0115423110.3390/metabo15040231Single-Nucleus RNA Sequencing Reveals Muscle-Region-Specific Differences in Fibro-Adipogenic Progenitors Driving Intramuscular Fat AccumulationShuji Ueda0Chiaki Kitamura1Yuka Tateoka2Akinori Kanai3Yutaka Suzuki4Itsuko Fukuda5Yasuhito Shirai6Graduate School of Agricultural Science, Kobe University, Kobe 657-8501, JapanGraduate School of Agricultural Science, Kobe University, Kobe 657-8501, JapanGraduate School of Agricultural Science, Kobe University, Kobe 657-8501, JapanGraduate School of Frontier Sciences, The University of Tokyo, Kashiwa 277-8562, JapanGraduate School of Frontier Sciences, The University of Tokyo, Kashiwa 277-8562, JapanGraduate School of Agricultural Science, Kobe University, Kobe 657-8501, JapanGraduate School of Agricultural Science, Kobe University, Kobe 657-8501, JapanBackground: Ectopic fat deposition refers to lipid accumulation that affects metabolic function and tissue characteristics. Japanese Black cattle are distinguished by their high intramuscular fat content, which contributes to their distinctive character. However, the genetic mechanisms underlying these traits remain unclear. This study compared gene expression patterns in different muscle regions to identify genes associated with intramuscular fat accumulation. First, we conducted RNA sequencing to analyze differences in gene expression profiles among the sternocleidomastoid, pectoralis minor, and pectoralis major muscles. In addition, single-cell nuclear RNA sequencing was conducted to investigate the cellular composition of these muscle tissues. Results: Distinct gene expression patterns were observed among the different muscles. In the pectoralis, which contains a high proportion of intramuscular fat, adipocyte-related genes such as <i>FABP4</i>, <i>SCD</i>, and <i>ADIPOQ</i> were highly expressed. In addition, lipases such as <i>PNPLA2</i>, <i>LPL</i>, <i>MGLL</i>, and <i>LIPE</i> were predominantly expressed in intramuscular fat, whereas <i>PLA2G12A</i>, <i>PLD3</i>, and <i>ALOX15</i> were specifically expressed in myofibers. Moreover, a subclass of fibro–adipogenic progenitor cells that differentiate into intramuscular adipocytes was found to express genes related to microenvironment formation, including <i>ICAM1</i>, <i>TGFBRs</i>, and members of the <i>COL4A</i> family. Conclusions: This study provides novel insight into the genetic regulation of intramuscular fat accumulation. It improves our understanding of the molecular mechanisms underlying their distinctive meat characteristics.https://www.mdpi.com/2218-1989/15/4/231intramuscular fatRNA sequencingFAPcollagenlipaseTGF-β |
| spellingShingle | Shuji Ueda Chiaki Kitamura Yuka Tateoka Akinori Kanai Yutaka Suzuki Itsuko Fukuda Yasuhito Shirai Single-Nucleus RNA Sequencing Reveals Muscle-Region-Specific Differences in Fibro-Adipogenic Progenitors Driving Intramuscular Fat Accumulation Metabolites intramuscular fat RNA sequencing FAP collagen lipase TGF-β |
| title | Single-Nucleus RNA Sequencing Reveals Muscle-Region-Specific Differences in Fibro-Adipogenic Progenitors Driving Intramuscular Fat Accumulation |
| title_full | Single-Nucleus RNA Sequencing Reveals Muscle-Region-Specific Differences in Fibro-Adipogenic Progenitors Driving Intramuscular Fat Accumulation |
| title_fullStr | Single-Nucleus RNA Sequencing Reveals Muscle-Region-Specific Differences in Fibro-Adipogenic Progenitors Driving Intramuscular Fat Accumulation |
| title_full_unstemmed | Single-Nucleus RNA Sequencing Reveals Muscle-Region-Specific Differences in Fibro-Adipogenic Progenitors Driving Intramuscular Fat Accumulation |
| title_short | Single-Nucleus RNA Sequencing Reveals Muscle-Region-Specific Differences in Fibro-Adipogenic Progenitors Driving Intramuscular Fat Accumulation |
| title_sort | single nucleus rna sequencing reveals muscle region specific differences in fibro adipogenic progenitors driving intramuscular fat accumulation |
| topic | intramuscular fat RNA sequencing FAP collagen lipase TGF-β |
| url | https://www.mdpi.com/2218-1989/15/4/231 |
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