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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Main Authors: Shuji Ueda, Chiaki Kitamura, Yuka Tateoka, Akinori Kanai, Yutaka Suzuki, Itsuko Fukuda, Yasuhito Shirai
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Metabolites
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Online Access:https://www.mdpi.com/2218-1989/15/4/231
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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
collection DOAJ
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.
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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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