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Metabolites
Volume 15
Issue 4
10.3390/metabo15040231
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Article

Single-Nucleus RNA Sequencing Reveals Muscle-Region-Specific Differences in Fibro-Adipogenic Progenitors Driving Intramuscular Fat Accumulation

by
Shuji Ueda
1,*,
Chiaki Kitamura
1,
Yuka Tateoka
1,
Akinori Kanai
2,
Yutaka Suzuki
2,
Itsuko Fukuda
1 and
Yasuhito Shirai
1
1
Graduate School of Agricultural Science, Kobe University, Kobe 657-8501, Japan
2
Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa 277-8562, Japan
*
Author to whom correspondence should be addressed.
Metabolites 2025, 15(4), 231; https://doi.org/10.3390/metabo15040231
Submission received: 7 March 2025 / Revised: 17 March 2025 / Accepted: 19 March 2025 / Published: 28 March 2025
(This article belongs to the Section Food Metabolomics)
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Abstract

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 FABP4, SCD, and ADIPOQ were highly expressed. In addition, lipases such as PNPLA2, LPL, MGLL, and LIPE were predominantly expressed in intramuscular fat, whereas PLA2G12A, PLD3, and ALOX15 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 ICAM1, TGFBRs, and members of the COL4A 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.
Keywords: intramuscular fat; RNA sequencing; FAP; collagen; lipase; TGF-β; COL4A; ICAM1; TOX intramuscular fat; RNA sequencing; FAP; collagen; lipase; TGF-β; COL4A; ICAM1; TOX
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MDPI and ACS Style

Ueda, S.; Kitamura, C.; Tateoka, Y.; Kanai, A.; Suzuki, Y.; Fukuda, I.; Shirai, Y. Single-Nucleus RNA Sequencing Reveals Muscle-Region-Specific Differences in Fibro-Adipogenic Progenitors Driving Intramuscular Fat Accumulation. Metabolites 2025, 15, 231. https://doi.org/10.3390/metabo15040231

AMA Style

Ueda S, Kitamura C, Tateoka Y, Kanai A, Suzuki Y, Fukuda I, Shirai Y. Single-Nucleus RNA Sequencing Reveals Muscle-Region-Specific Differences in Fibro-Adipogenic Progenitors Driving Intramuscular Fat Accumulation. Metabolites. 2025; 15(4):231. https://doi.org/10.3390/metabo15040231

Chicago/Turabian Style

Ueda, Shuji, Chiaki Kitamura, Yuka Tateoka, Akinori Kanai, Yutaka Suzuki, Itsuko Fukuda, and Yasuhito Shirai. 2025. "Single-Nucleus RNA Sequencing Reveals Muscle-Region-Specific Differences in Fibro-Adipogenic Progenitors Driving Intramuscular Fat Accumulation" Metabolites 15, no. 4: 231. https://doi.org/10.3390/metabo15040231

APA Style

Ueda, S., Kitamura, C., Tateoka, Y., Kanai, A., Suzuki, Y., Fukuda, I., & Shirai, Y. (2025). Single-Nucleus RNA Sequencing Reveals Muscle-Region-Specific Differences in Fibro-Adipogenic Progenitors Driving Intramuscular Fat Accumulation. Metabolites, 15(4), 231. https://doi.org/10.3390/metabo15040231

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