Integrative Cross-species Analysis Reveals Conserved and Unique Signatures in Fatty Skeletal Muscles

Overview

Journal Sci Data

Specialty Science

Date 2024 Mar 13

PMID 38472209

Authors

Liyi Wang

Yanbing Zhou

Yizhen Wang

Tizhong Shan

Affiliations

Soon will be listed here.

Abstract

Fat infiltration in skeletal muscle is now recognized as a standard feature of aging and is directly related to the decline in muscle function. However, there is still a limited systematic integration and exploration of the mechanisms underlying the occurrence of myosteatosis in aging across species. Here, we re-analyzed bulk RNA-seq datasets to investigate the association between fat infiltration in skeletal muscle and aging. Our integrated analysis of single-nucleus transcriptomics in aged humans and Laiwu pigs with high intramuscular fat content, identified species-preference subclusters and revealed core gene programs associated with myosteatosis. Furthermore, we found that fibro/adipogenic progenitors (FAPs) had potential capacity of differentiating into PDE4D/PDE7B preadipocytes across species. Additionally, cell-cell communication analysis revealed that FAPs may be associated with other adipogenic potential clusters via the COL4A2 and COL6A3 pathways. Our study elucidates the correlation mechanism between aging and fat infiltration in skeletal muscle, and these consensus signatures in both humans and pigs may contribute to increasing reproducibility and reliability in future studies involving in the field of muscle research.

Citing Articles

Single-Nucleus RNA Sequencing Reveals Cellular Transcriptome Features at Different Growth Stages in Porcine Skeletal Muscle.

Chen Z, Wu X, Zheng D, Wang Y, Chai J, Zhang T Cells. 2025; 14(1.

PMID: 39791738 PMC: 11720419. DOI: 10.3390/cells14010037.

References

Biltz N, Collins K, Shen K, Schwartz K, Harris C, Meyer G . Infiltration of intramuscular adipose tissue impairs skeletal muscle contraction. J Physiol. 2020; 598(13):2669-2683. PMC: 8767374. DOI: 10.1113/JP279595. View

Tieland M, Trouwborst I, Clark B . Skeletal muscle performance and ageing. J Cachexia Sarcopenia Muscle. 2017; 9(1):3-19. PMC: 5803609. DOI: 10.1002/jcsm.12238. View

Zammit P . Function of the myogenic regulatory factors Myf5, MyoD, Myogenin and MRF4 in skeletal muscle, satellite cells and regenerative myogenesis. Semin Cell Dev Biol. 2017; 72:19-32. DOI: 10.1016/j.semcdb.2017.11.011. View

Wang L, Zhao X, Liu S, You W, Huang Y, Zhou Y . Single-nucleus and bulk RNA sequencing reveal cellular and transcriptional mechanisms underlying lipid dynamics in high marbled pork. NPJ Sci Food. 2023; 7(1):23. PMC: 10238404. DOI: 10.1038/s41538-023-00203-4. View

Bourin P, Bunnell B, Casteilla L, Dominici M, Katz A, March K . Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the.... Cytotherapy. 2013; 15(6):641-8. PMC: 3979435. DOI: 10.1016/j.jcyt.2013.02.006. View

Petrany M, Swoboda C, Sun C, Chetal K, Chen X, Weirauch M . Single-nucleus RNA-seq identifies transcriptional heterogeneity in multinucleated skeletal myofibers. Nat Commun. 2020; 11(1):6374. PMC: 7733460. DOI: 10.1038/s41467-020-20063-w. View

Bentzinger C, Wang Y, Rudnicki M . Building muscle: molecular regulation of myogenesis. Cold Spring Harb Perspect Biol. 2012; 4(2). PMC: 3281568. DOI: 10.1101/cshperspect.a008342. View

Laurentius T, Kob R, Fellner C, Nourbakhsh M, Bertsch T, Sieber C . Long-Chain Fatty Acids and Inflammatory Markers Coaccumulate in the Skeletal Muscle of Sarcopenic Old Rats. Dis Markers. 2019; 2019:9140789. PMC: 6636585. DOI: 10.1155/2019/9140789. View

Koch M, Schulze J, Hansen U, Ashwodt T, Keene D, Brunken W . A novel marker of tissue junctions, collagen XXII. J Biol Chem. 2004; 279(21):22514-21. PMC: 2925840. DOI: 10.1074/jbc.M400536200. View

10.

Ubaida-Mohien C, Lyashkov A, Gonzalez-Freire M, Tharakan R, Shardell M, Moaddel R . Discovery proteomics in aging human skeletal muscle finds change in spliceosome, immunity, proteostasis and mitochondria. Elife. 2019; 8. PMC: 6810669. DOI: 10.7554/eLife.49874. View

11.

Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S . PRDM16 controls a brown fat/skeletal muscle switch. Nature. 2008; 454(7207):961-7. PMC: 2583329. DOI: 10.1038/nature07182. View

12.

Li C, Yu K, Shyh-Chang N, Jiang Z, Liu T, Ma S . Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review. J Cachexia Sarcopenia Muscle. 2022; 13(2):781-794. PMC: 8977978. DOI: 10.1002/jcsm.12901. View

13.

Joe A, Yi L, Natarajan A, Le Grand F, So L, Wang J . Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis. Nat Cell Biol. 2010; 12(2):153-63. PMC: 4580288. DOI: 10.1038/ncb2015. View

14.

Jiang Z, Marriott K, Maly M . Impact of Inter- and Intramuscular Fat on Muscle Architecture and Capacity. Crit Rev Biomed Eng. 2020; 47(6):515-533. DOI: 10.1615/CritRevBiomedEng.2020031124. View

15.

Wosczyna M, Perez Carbajal E, Wagner M, Paredes S, Konishi C, Liu L . Targeting microRNA-mediated gene repression limits adipogenic conversion of skeletal muscle mesenchymal stromal cells. Cell Stem Cell. 2021; 28(7):1323-1334.e8. PMC: 8254802. DOI: 10.1016/j.stem.2021.04.008. View

16.

La Manno G, Soldatov R, Zeisel A, Braun E, Hochgerner H, Petukhov V . RNA velocity of single cells. Nature. 2018; 560(7719):494-498. PMC: 6130801. DOI: 10.1038/s41586-018-0414-6. View

17.

Bergen V, Lange M, Peidli S, Wolf F, Theis F . Generalizing RNA velocity to transient cell states through dynamical modeling. Nat Biotechnol. 2020; 38(12):1408-1414. DOI: 10.1038/s41587-020-0591-3. View

18.

Jing Y, Zuo Y, Yu Y, Sun L, Yu Z, Ma S . Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging. Protein Cell. 2023; 14(7):497-512. PMC: 10305740. DOI: 10.1093/procel/pwac061. View

19.

Wang L, Valencak T, Shan T . Fat infiltration in skeletal muscle: Influential triggers and regulatory mechanism. iScience. 2024; 27(3):109221. PMC: 10907799. DOI: 10.1016/j.isci.2024.109221. View

20.

Uezumi A, Fukada S, Yamamoto N, Takeda S, Tsuchida K . Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle. Nat Cell Biol. 2010; 12(2):143-52. DOI: 10.1038/ncb2014. View