Multiomics reveals glutathione metabolism as a driver of bimodality during stem cell aging PY2023 IR95 教材

Multiomics reveals glutathione metabolism as a driver of bimodality during stem cell aging PY2023 IR95 教材

--- -  - --- -  - ---
2025-11-04
Multiomics reveals glutathione metabolism as a driver of bimodality during stem cell aging

Source or References (資訊來源或是參考的資訊):
https://pubmed.ncbi.nlm.nih.gov/36854304/
Info cited on 2025-11-04-WD2 (資訊引用於 中華民國114年西元2025年11月4日) by 湯偉晉 (WeiJin Tang)
#

- -  - - - -  - -

Cell Metab
. 2023 Mar 7;35(3):472-486.e6. doi: 10.1016/j.cmet.2023.02.001. Epub 2023 Feb 27.
Multiomics reveals glutathione metabolism as a driver of bimodality during stem cell aging
Daniel I Benjamin 1, Jamie O Brett 2, Pieter Both 3, Joel S Benjamin 1, Heather L Ishak 4, Jengmin Kang 1, Soochi Kim 1, Mingyu Chung 1, Marina Arjona 1, Christopher W Nutter 4, Jenna H Tan 4, Ananya K Krishnan 4, Hunter Dulay 4, Sharon M Louie 5, Antoine de Morree 1, Daniel K Nomura 5, Thomas A Rando 6
Affiliations expand
PMID: 36854304 PMCID: PMC10015599 DOI: 10.1016/j.cmet.2023.02.001

Abstract
With age, skeletal muscle stem cells (MuSCs) activate out of quiescence more slowly and with increased death, leading to defective muscle repair. To explore the molecular underpinnings of these defects, we combined multiomics, single-cell measurements, and functional testing of MuSCs from young and old mice. The multiomics approach allowed us to assess which changes are causal, which are compensatory, and which are simply correlative. We identified glutathione (GSH) metabolism as perturbed in old MuSCs, with both causal and compensatory components. Contrary to young MuSCs, old MuSCs exhibit a population dichotomy composed of GSHhigh cells (comparable with young MuSCs) and GSHlow cells with impaired functionality. Mechanistically, we show that antagonism between NRF2 and NF-κB maintains this bimodality. Experimental manipulation of GSH levels altered the functional dichotomy of aged MuSCs. These findings identify a novel mechanism of stem cell aging and highlight glutathione metabolism as an accessible target for reversing MuSC aging.
##
Abstract
摘要

With age, skeletal muscle stem cells (MuSCs) activate out of quiescence more slowly and with increased death, leading to defective muscle repair.
隨著年齡增長，骨骼肌幹細胞（MuSCs）從靜止狀態活化的速度變慢，且死亡率增加，導致肌肉修復功能受損。

molecular underpinnings
底層分子機制

To explore the molecular underpinnings of these defects, we combined multiomics, single-cell measurements, and functional testing of MuSCs from young and old mice.
為了探究這些缺陷的分子基礎，我們結合了多組學（multiomics）、單細胞測量以及來自年輕和老鼠的MuSCs功能測試。

The multiomics approach allowed us to assess which changes are causal, which are compensatory, and which are simply correlative.
多組學方法使我們能夠評估哪些變化是因果關係、哪些是補償性改變，以及哪些僅是相關性現象。

We identified glutathione (GSH) metabolism as perturbed in old MuSCs, with both causal and compensatory components.
我們發現老年MuSCs的穀胱甘肽（GSH）代謝受到干擾，其中包含因果性和補償性成分。

Contrary to young MuSCs, old MuSCs exhibit a population dichotomy composed of GSHhigh cells (comparable with young MuSCs) and GSHlow cells with impaired functionality.
與年輕MuSCs不同，老年MuSCs呈現細胞群體二分化：包含GSH高（GSHhigh）細胞（功能與年輕MuSCs相當）和GSH低（GSHlow）細胞（功能受損）。

Mechanistically, we show that antagonism between NRF2 and NF-κB maintains this bimodality.
在機制上，我們證明NRF2與NF-κB之間的拮抗作用維持了這種雙模態（bimodality）。

Experimental manipulation of GSH levels altered the functional dichotomy of aged MuSCs.
實驗中對GSH水準的調控改變了老年MuSCs的功能二分化現象。

These findings identify a novel mechanism of stem cell aging and highlight glutathione metabolism as an accessible target for reversing MuSC aging.
這些發現揭示了一種幹細胞衰老的新機制，並強調穀胱甘肽代謝可作為一個可操作的目標，用於逆轉MuSC的老化。

##
Keywords: GSH; MuSC; NAC; aging; bimodality; multiomics; satellite cells; stem cells.

Published by Elsevier Inc.

PubMed Disclaimer

Conflict of interest statement
Declaration of interests The authors declare no competing interests.

Figures
Figure 1.
Figure 1.. Multiomics identifies glutathione metabolism as…

Figure 2.
Figure 2.. The bulk population of old…

Figure 3.
Figure 3.. GSH levels causally determine MuSC…

Figure 4.
Figure 4.. Transcriptomic profiling of GSH high …

Figure 5.
Figure 5.. NF-κB AMO treatment and old…
Comment in
Rejuvenating muscle stem cells with the glutathione system.
Forcina L, Musarò A.
Cell Metab. 2023 Mar 7;35(3):379-381. doi: 10.1016/j.cmet.2023.02.009.
PMID: 36889277
Similar articles
The hypothalamic-pituitary-gonadal axis controls muscle stem cell senescence through autophagosome clearance.
Kim JH, Park I, Shin HR, Rhee J, Seo JY, Jo YW, Yoo K, Hann SH, Kang JS, Park J, Kim YL, Moon JY, Choi MH, Kong YY.
J Cachexia Sarcopenia Muscle. 2021 Feb;12(1):177-191. doi: 10.1002/jcsm.12653. Epub 2020 Nov 27.
PMID: 33244887Free PMC article.
Aerobic exercise suppresses CCN2 secretion from senescent muscle stem cells and boosts muscle regeneration in aged mice.
Li F, Zhang F, Shi H, Xia H, Wei X, Liu S, Wu T, Li Y, Shu F, Chen M, Li J, Duan R.
J Cachexia Sarcopenia Muscle. 2024 Oct;15(5):1733-1749. doi: 10.1002/jcsm.13526. Epub 2024 Jun 26.
PMID: 38925632Free PMC article.
The mini-IDLE 3D biomimetic culture assay enables interrogation of mechanisms governing muscle stem cell quiescence and niche repopulation.
Jacques E, Kuang Y, Kann AP, Le Grand F, Krauss RS, Gilbert PM.
Elife. 2022 Dec 20;11:e81738. doi: 10.7554/eLife.81738.
PMID: 36537758Free PMC article.
Stem Cell Aging in Skeletal Muscle Regeneration and Disease.
Yamakawa H, Kusumoto D, Hashimoto H, Yuasa S.
Int J Mol Sci. 2020 Mar 6;21(5):1830. doi: 10.3390/ijms21051830.
PMID: 32155842Free PMC article.Review.
Decline of regenerative potential of old muscle stem cells: contribution to muscle aging.
Sahinyan K, Lazure F, Blackburn DM, Soleimani VD.
FEBS J. 2023 Mar;290(5):1267-1289. doi: 10.1111/febs.16352. Epub 2022 Jan 25.
PMID: 35029021Review.
See all similar articles
Cited by
A framework of biomarkers for skeletal muscle aging: a consensus statement by the Aging Biomarker Consortium.
Aging Biomarker Consortium; Huang N, Ge M, Liu X, Tian X, Yin P, Bao Z, Cao F, Shyh-Chang N, Dong B, Dai L, Gan Z, Hu P, Qu J, Wang S, Wang H, Xiao Q, Yue R, Yue J, Zhang L, Zhang Y, Zhang H, Zhang W, Liu GH, Pei G, Liu Y, Zhu D, Dong B.
Life Med. 2025 Jan 26;3(6):lnaf001. doi: 10.1093/lifemedi/lnaf001. eCollection 2024 Dec.
PMID: 40008206Free PMC article.
Epigenetic erosion of H4K20me1 induced by inflammation drives aged stem cell ferroptosis.
Blanc RS, Shah N, Hachmer S, Salama NAS, Meng FW, Mousaei A, Puri G, Hwang JH, Wacker EE, Yang BA, Aguilar CA, Chakkalakal JV, Onukwufor JO, Murphy PJ, Calvi LM, Dilworth FJ, Dirksen RT.
Nat Aging. 2025 Aug;5(8):1491-1509. doi: 10.1038/s43587-025-00902-5. Epub 2025 Jun 30.
PMID: 40588650Free PMC article.
Skeletal stem cells, a new direction for the treatment of bone and joint diseases.
Liu C, Jian J, Yi YF, Ding YT, Chen Y, Tang ZW, Wen J, Li YF.
World J Orthop. 2025 Aug 18;16(8):108407. doi: 10.5312/wjo.v16.i8.108407. eCollection 2025 Aug 18.
PMID: 40838219Free PMC article.Review.
Cystine/glutamate antiporter xCT controls skeletal muscle glutathione redox, bioenergetics and differentiation.
Kanaan MN, Pileggi CA, Karam CY, Kennedy LS, Fong-McMaster C, Cuperlovic-Culf M, Harper ME.
Redox Biol. 2024 Jul;73:103213. doi: 10.1016/j.redox.2024.103213. Epub 2024 May 25.
PMID: 38815331Free PMC article.
Glutathione restoration: a sword to combat skeletal muscle stem cell aging.
Wu Z, Ren J, Liu GH.
Life Metab. 2023 Mar 31;2(3):load012. doi: 10.1093/lifemeta/load012. eCollection 2023 Jun.
PMID: 39872012Free PMC article.No abstract available.
See all "Cited by" articles
References
Pomatto LCD, and Davies KJA (2017). The role of declining adaptive homeostasis in ageing. J. Physiol. 595, 7275–7309. 10.1113/jp275072. - DOI - PMC - PubMed
Hayflick L (2007). Biological aging is no longer an unsolved problem. Ann. N. Y. Acad. Sci. 1100, 1–13. 10.1196/annals.1395.001. - DOI - PubMed
Gladyshev VN (2012). On the cause of aging and control of lifespan: heterogeneity leads to inevitable damage accumulation, causing aging; control of damage composition and rate of accumulation define lifespan. Bioessays 34, 925–929. 10.1002/bies.201200092. - DOI - PMC - PubMed
Todhunter ME, Sayaman RW, Miyano M, and LaBarge MA (2018). Tissue aging: the integration of collective and variant responses of cells to entropic forces over time. Curr. Opin. Cell Biol. 54, 121–129. 10.1016/j.ceb.2018.05.016. - DOI - PMC - PubMed
Mahmoudi S, Mancini E, Xu L, Moore A, Jahanbani F, Hebestreit K, Srinivasan R, Li X, Devarajan K, Prélot L, et al. (2019). Heterogeneity in old fibroblasts is linked to variability in reprogramming and wound healing. Nature 574, 553–558. 10.1038/s41586-019-1658-5. - DOI - PMC - PubMed
Gladyshev VN (2014). The free radical theory of aging is dead. Long live the damage theory! Antioxid. Redox Signal. 20, 727–731. 10.1089/ars.2013.5228. - DOI - PMC - PubMed
Barzilai N, Cuervo AM, and Austad S (2018). Aging as a Biological Target for Prevention and Therapy. JAMA 320, 1321–1322. 10.1001/jama.2018.9562. - DOI - PubMed
Holliday R (2006). Aging is no longer an unsolved problem in biology. Ann. N. Y. Acad. Sci. 1067, 1–9. 10.1196/annals.1354.002. - DOI - PubMed
Miller RA (2002). Extending life: scientific prospects and political obstacles. Milbank Q. 80, 155–174. 10.1111/1468-0009.00006. - DOI - PMC - PubMed
Holliday R (2009). The extreme arrogance of anti-aging medicine. Biogerontology 10, 223–228. 10.1007/s10522-008-9170-6. - DOI - PubMed
Conboy IM, Conboy MJ, Smythe GM, and Rando TA (2003). Notch-mediated restoration of regenerative potential to aged muscle. Science 302, 1575–1577. 10.1126/science.1087573. - DOI - PubMed
Brack AS, and Muñoz-Cánoves P (2016). The ins and outs of muscle stem cell aging. Skelet. Muscle 6, 1. 10.1186/s13395-016-0072-z. - DOI - PMC - PubMed
Muñoz-Cánoves P, Neves J, and Sousa-Victor P (2020). Understanding muscle regenerative decline with aging: new approaches to bring back youthfulness to aged stem cells. FEBS J. 287, 406–416. 10.1111/febs.15182. - DOI - PubMed
Schwörer S, Becker F, Feller C, Baig AH, Köber U, Henze H, Kraus JM, Xin B, Lechel A, Lipka DB, et al. (2016). Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals. Nature 540, 428–432. 10.1038/nature20603. - DOI - PMC - PubMed
Liu L, Cheung TH, Charville GW, Hurgo BMC, Leavitt T, Shih J, Brunet A, and Rando TA (2013). Chromatin modifications as determinants of muscle stem cell quiescence and chronological aging. Cell Rep. 4, 189–204. 10.1016/j.celrep.2013.05.043. - DOI - PMC - PubMed
Hernando-Herraez I, Evano B, Stubbs T, Commere P-H, Jan Bonder M, Clark S, Andrews S, Tajbakhsh S, and Reik W (2019). Ageing affects DNA methylation drift and transcriptional cell-to-cell variability in mouse muscle stem cells. Nat. Commun. 10, 4361. 10.1038/s41467-019-12293-4. - DOI - PMC - PubMed
Solanas G, Peixoto FO, Perdiguero E, Jardí M, Ruiz-Bonilla V, Datta D, Symeonidi A, Castellanos A, Welz P-S, Caballero JM, et al. (2017). Aged Stem Cells Reprogram Their Daily Rhythmic Functions to Adapt to Stress. Cell 170, 678–692.e20. 10.1016/j.cell.2017.07.035. - DOI - PubMed
Pala F, Di Girolamo D, Mella S, Yennek S, Chatre L, Ricchetti M, and Tajbakhsh S (2018). Distinct metabolic states govern skeletal muscle stem cell fates during prenatal and postnatal myogenesis. J. Cell Sci. 131. 10.1242/jcs.212977. - DOI - PMC - PubMed
Lukjanenko L, Jung MJ, Hegde N, Perruisseau-Carrier C, Migliavacca E, Rozo M, Karaz S, Jacot G, Schmidt M, Li L, et al. (2016). Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice. Nat. Med. 22, 897–905. 10.1038/nm.4126. - DOI - PMC - PubMed
Sousa-Victor P, Gutarra S, García-Prat L, Rodriguez-Ubreva J, Ortet L, Ruiz-Bonilla V, Jardí M, Ballestar E, González S, Serrano AL, et al. (2014). Geriatric muscle stem cells switch reversible quiescence into senescence. Nature 506, 316–321. 10.1038/nature13013. - DOI - PubMed
Bernet JD, Doles JD, Hall JK, Kelly Tanaka K, Carter TA, and Olwin BB (2014). p38 MAPK signaling underlies a cell-autonomous loss of stem cell self-renewal in skeletal muscle of aged mice. Nat. Med. 20, 265–271. 10.1038/nm.3465. - DOI - PMC - PubMed
Brett JO, Arjona M, Ikeda M, Quarta M, de Morrée A, Egner IM, Perandini LA, Ishak HD, Goshayeshi A, Benjamin DI, et al. (2020). Exercise rejuvenates quiescent skeletal muscle stem cells in old mice through restoration of Cyclin D1. Nat. Metab. 2, 307–317. 10.1038/s42255-020-0190-0. - DOI - PMC - PubMed
Shcherbina A, Larouche J, Fraczek P, Yang BA, Brown LA, Markworth JF, Chung CH, Khaliq M, de Silva K, Choi JJ, et al. (2020). Dissecting Murine Muscle Stem Cell Aging through Regeneration Using Integrative Genomic Analysis. Cell Rep. 32, 107964. 10.1016/j.celrep.2020.107964. - DOI - PMC - PubMed
Liu L, Charville GW, Cheung TH, Yoo B, Santos PJ, Schroeder M, and Rando TA (2018). Impaired Notch Signaling Leads to a Decrease in p53 Activity and Mitotic Catastrophe in Aged Muscle Stem Cells. Cell Stem Cell 23, 544–556.e4. 10.1016/j.stem.2018.08.019. - DOI - PMC - PubMed
Tierney MT, Stec MJ, Rulands S, Simons BD, and Sacco A (2018). Muscle Stem Cells Exhibit Distinct Clonal Dynamics in Response to Tissue Repair and Homeostatic Aging. Cell Stem Cell 22, 119–127.e3. 10.1016/j.stem.2017.11.009. - DOI - PMC - PubMed
Li L, Rozo M, Yue S, Zheng X, Tan F, Lepper C, and Fan C-M (2019). Muscle stem cell renewal suppressed by Gas1 can be reversed by GDNF in mice. Nat. Metab. 1, 985–995. 10.1038/s42255-019-0110-3. - DOI - PMC - PubMed
Kimmel JC, Hwang AB, Scaramozza A, Marshall WF, and Brack AS (2020). Aging induces aberrant state transition kinetics in murine muscle stem cells. Development 147. 10.1242/dev.183855. - DOI - PMC - PubMed
Chakkalakal JV, Jones KM, Basson MA, and Brack AS (2012). The aged niche disrupts muscle stem cell quiescence. Nature 490, 355–360. 10.1038/nature11438. - DOI - PMC - PubMed
Bou Sleiman M, Jha P, Houtkooper R, Williams RW, Wang X, and Auwerx J (2020). The Gene-Regulatory Footprint of Aging Highlights Conserved Central Regulators. Cell Rep. 32, 108203. 10.1016/j.celrep.2020.108203. - DOI - PMC - PubMed
Machado L, Esteves de Lima J, Fabre O, Proux C, Legendre R, Szegedi A, Varet H, Ingerslev LR, Barrès R, Relaix F, et al. (2017). In Situ Fixation Redefines Quiescence and Early Activation of Skeletal Muscle Stem Cells. Cell Rep. 21, 1982–1993. 10.1016/j.celrep.2017.10.080. - DOI - PubMed
Horvath S, and Raj K (2018). DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat. Rev. Genet. 19, 371–384. 10.1038/s41576-018-0004-3. - DOI - PubMed
Wu H, Wang C, and Wu Z (2013). A new shrinkage estimator for dispersion improves differential expression detection in RNA-seq data. Biostatistics 14, 232–243. 10.1093/biostatistics/kxs033. - DOI - PMC - PubMed
Ziller MJ, Gu H, Müller F, Donaghey J, Tsai LT-Y, Kohlbacher O, De Jager PL, Rosen ED, Bennett DA, Bernstein BE, et al. (2013). Charting a dynamic DNA methylation landscape of the human genome. Nature 500, 477–481. 10.1038/nature12433. - DOI - PMC - PubMed
Sun D, Luo M, Jeong M, Rodriguez B, Xia Z, Hannah R, Wang H, Le T, Faull KF, Chen R, et al. (2014). Epigenomic profiling of young and aged HSCs reveals concerted changes during aging that reinforce self-renewal. Cell Stem Cell 14, 673–688. 10.1016/j.stem.2014.03.002. - DOI - PMC - PubMed
Weber M, Hellmann I, Stadler MB, Ramos L, Pääbo S, Rebhan M, and Schübeler D (2007). Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat. Genet. 39, 457–466. 10.1038/ng1990. - DOI - PubMed
Brinkman AB, Gu H, Bartels SJJ, Zhang Y, Matarese F, Simmer F, Marks H, Bock C, Gnirke A, Meissner A, et al. (2012). Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk. Genome Res. 22, 1128–1138. 10.1101/gr.133728.111. - DOI - PMC - PubMed
Manzo M, Wirz J, Ambrosi C, Villaseñor R, Roschitzki B, and Baubec T (2017). Isoform-specific localization of DNMT3A regulates DNA methylation fidelity at bivalent CpG islands. EMBO J. 36, 3421–3434. 10.15252/embj.201797038. - DOI - PMC - PubMed
Viré E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C, Morey L, Van Eynde A, Bernard D, Vanderwinden J-M, et al. (2006). The Polycomb group protein EZH2 directly controls DNA methylation. Nature 439, 871–874. 10.1038/nature04431. - DOI - PubMed
Statham AL, Robinson MD, Song JZ, Coolen MW, Stirzaker C, and Clark SJ (2012). Bisulfite sequencing of chromatin immunoprecipitated DNA (BisChIP-seq) directly informs methylation status of histone-modified DNA. Genome Res. 22, 1120–1127. 10.1101/gr.132076.111. - DOI - PMC - PubMed
Tanay A, O’Donnell AH, Damelin M, and Bestor TH (2007). Hyperconserved CpG domains underlie Polycomb-binding sites. Proc. Natl. Acad. Sci. U. S. A. 104, 5521–5526. 10.1073/pnas.0609746104. - DOI - PMC - PubMed
Lindroth AM, Park YJ, McLean CM, Dokshin GA, Persson JM, Herman H, Pasini D, Miró X, Donohoe ME, Lee JT, et al. (2008). Antagonism between DNA and H3K27 methylation at the imprinted Rasgrf1 locus. PLoS Genet. 4, e1000145. 10.1371/journal.pgen.1000145. - DOI - PMC - PubMed
Boulard M, Edwards JR, and Bestor TH (2015). FBXL10 protects Polycomb-bound genes from hypermethylation. Nat. Genet. 47, 479–485. 10.1038/ng.3272. - DOI - PubMed
Zhao X, Wang X, Li Q, Chen W, Zhang N, Kong Y, Lv J, Cao L, Lin D, Wang X, et al. (2018). FBXL10 contributes to the development of diffuse large B-cell lymphoma by epigenetically enhancing ERK1/2 signaling pathway. Cell Death Dis. 9, 46. 10.1038/s41419-017-0066-8. - DOI - PMC - PubMed
Eichenfield DZ, Troutman TD, Link VM, Lam MT, Cho H, Gosselin D, Spann NJ, Lesch HP, Tao J, Muto J, et al. (2016). Tissue damage drives co-localization of NF-κB, Smad3, and Nrf2 to direct Rev-erb sensitive wound repair in mouse macrophages. Elife 5. 10.7554/eLife.13024. - DOI - PMC - PubMed
Benayoun BA, Pollina EA, Ucar D, Mahmoudi S, Karra K, Wong ED, Devarajan K, Daugherty AC, Kundaje AB, Mancini E, et al. (2014). H3K4me3 breadth is linked to cell identity and transcriptional consistency. Cell 158, 673–688. 10.1016/j.cell.2014.06.027. - DOI - PMC - PubMed
Kanehisa M, and Goto S (2000). KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27–30. 10.1093/nar/28.1.27. - DOI - PMC - PubMed
Pinu FR, Beale DJ, Paten AM, Kouremenos K, Swarup S, Schirra HJ, and Wishart D (2019). Systems Biology and Multi-Omics Integration: Viewpoints from the Metabolomics Research Community. Metabolites 9. 10.3390/metabo9040076. - DOI - PMC - PubMed
Pihur V, Datta S, and Datta S (2009). RankAggreg, an R package for weighted rank aggregation. BMC Bioinformatics 10, 62. 10.1186/1471-2105-10-62. - DOI - PMC - PubMed
Kolde R, Laur S, Adler P, and Vilo J (2012). Robust rank aggregation for gene list integration and meta-analysis. Bioinformatics 28, 573–580. 10.1093/bioinformatics/btr709. - DOI - PMC - PubMed
Mandavilli BS, and Janes MS (2010). Detection of intracellular glutathione using ThiolTracker violet stain and fluorescence microscopy. Curr. Protoc. Cytom. Chapter 9, Unit 9.35. 10.1002/0471142956.cy0935s53. - DOI - PubMed
Killackey SA, Philpott DJ, and Girardin SE (2020). Mitophagy pathways in health and disease. J. Cell Biol. 219. 10.1083/jcb.202004029. - DOI - PMC - PubMed
Forman HJ, Zhang H, and Rinna A (2009). Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol. Aspects Med. 30, 1–12. 10.1016/j.mam.2008.08.006. - DOI - PMC - PubMed
Köhler E, Barrach H-J, and Neubert D (1970). Inhibition of NADP dependent oxidoreductases by the 6-aminonicotinamide analogue of NADP. FEBS Lett. 6, 225–228. 10.1016/0014-5793(70)80063-1. - DOI - PubMed
Griffith OW, and Meister A (1979). Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine). J. Biol. Chem. 254, 7558–7560. - PubMed
Xie X, Lu J, Kulbokas EJ, Golub TR, Mootha V, Lindblad-Toh K, Lander ES, and Kellis M (2005). Systematic discovery of regulatory motifs in human promoters and 3’ UTRs by comparison of several mammals. Nature 434, 338–345. 10.1038/nature03441. - DOI - PMC - PubMed
Adler AS, Sinha S, Kawahara TLA, Zhang JY, Segal E, and Chang HY (2007). Motif module map reveals enforcement of aging by continual NF-kappaB activity. Genes Dev. 21, 3244–3257. 10.1101/gad.1588507. - DOI - PMC - PubMed
Tilstra JS, Robinson AR, Wang J, Gregg SQ, Clauson CL, Reay DP, Nasto LA, St Croix CM, Usas A, Vo N, et al. (2012). NF-κB inhibition delays DNA damage-induced senescence and aging in mice. J. Clin. Invest. 122, 2601–2612. 10.1172/JCI45785. - DOI - PMC - PubMed
Carlson ME, Hsu M, and Conboy IM (2008). Imbalance between pSmad3 and Notch induces CDK inhibitors in old muscle stem cells. Nature 454, 528–532. 10.1038/nature07034. - DOI - PMC - PubMed
Wardyn JD, Ponsford AH, and Sanderson CM (2015). Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways. Biochem. Soc. Trans. 43, 621–626. 10.1042/BST20150014. - DOI - PMC - PubMed
Oh J, Sinha I, Tan KY, Rosner B, Dreyfuss JM, Gjata O, Tran P, Shoelson SE, and Wagers AJ (2016). Age-associated NF-κB signaling in myofibers alters the satellite cell niche and re-strains muscle stem cell function. Aging (Albany. NY). 8, 2871–2896. 10.18632/aging.101098. - DOI - PMC - PubMed
Straughn AR, Hindi SM, Xiong G, and Kumar A (2019). Canonical NF-κB signaling regulates satellite stem cell homeostasis and function during regenerative myogenesis. J. Mol. Cell Biol. 11, 53–66. 10.1093/jmcb/mjy053. - DOI - PubMed
Shin H-M, Kim M-H, Kim BH, Jung S-H, Kim YS, Park HJ, Hong JT, Min KR, and Kim Y (2004). Inhibitory action of novel aromatic diamine compound on lipopolysaccharide-induced nuclear translocation of NF-kappaB without affecting IkappaB degradation. FEBS Lett. 571, 50–54. 10.1016/j.febslet.2004.06.056. - DOI - PubMed
Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, and Rando TA (2005). Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433, 760–764. 10.1038/nature03260. - DOI - PubMed
Conboy IM, and Rando TA (2012). Heterochronic parabiosis for the study of the effects of aging on stem cells and their niches. Cell Cycle 11, 2260–2267. 10.4161/cc.20437. - DOI - PMC - PubMed
Brandman O, and Meyer T (2008). Feedback loops shape cellular signals in space and time. Science 322, 390–395. 10.1126/science.1160617. - DOI - PMC - PubMed
Chung M, Liu C, Yang HW, Köberlin MS, Cappell SD, and Meyer T (2019). Transient Hysteresis in CDK4/6 Activity Underlies Passage of the Restriction Point in G1. Mol. Cell 76, 562–573.e4. 10.1016/j.molcel.2019.08.020. - DOI - PMC - PubMed
Prestigiacomo V, and Suter-Dick L (2018). Nrf2 protects stellate cells from Smad-dependent cell activation. PLoS One 13, e0201044. 10.1371/journal.pone.0201044. - DOI - PMC - PubMed
Gañán-Gómez I, Wei Y, Yang H, Boyano-Adánez MC, and García-Manero G (2013). Oncogenic functions of the transcription factor Nrf2. Free Radic. Biol. Med. 65, 750–764. 10.1016/j.freeradbiomed.2013.06.041. - DOI - PubMed
Christov C, Chrétien F, Abou-Khalil R, Bassez G, Vallet G, Authier F-J, Bassaglia Y, Shinin V, Tajbakhsh S, Chazaud B, et al. (2007). Muscle satellite cells and endothelial cells: close neighbors and privileged partners. Mol. Biol. Cell 18, 1397–1409. 10.1091/mbc.e06-08-0693. - DOI - PMC - PubMed
Verma M, Asakura Y, Murakonda BSR, Pengo T, Latroche C, Chazaud B, McLoon LK, and Asakura A (2018). Muscle Satellite Cell Cross-Talk with a Vascular Niche Maintains Quiescence via VEGF and Notch Signaling. Cell Stem Cell 23, 530–543.e9. 10.1016/j.stem.2018.09.007. - DOI - PMC - PubMed
Du H, Shih C-H, Wosczyna MN, Mueller AA, Cho J, Aggarwal A, Rando TA, and Feldman BJ (2017). Macrophage-released ADAMTS1 promotes muscle stem cell activation. Nat. Commun. 8, 669. 10.1038/s41467-017-00522-7. - DOI - PMC - PubMed
Murphy MM, Lawson JA, Mathew SJ, Hutcheson DA, and Kardon G (2011). Satellite cells, connective tissue fibroblasts and their interactions are crucial for muscle regeneration. Development 138, 3625–3637. 10.1242/dev.064162. - DOI - PMC - PubMed
Wosczyna MN, Konishi CT, Perez Carbajal EE, Wang TT, Walsh RA, Gan Q, Wagner MW, and Rando TA (2019). Mesenchymal Stromal Cells Are Required for Regeneration and Homeostatic Maintenance of Skeletal Muscle. Cell Rep. 27, 2029–2035.e5. 10.1016/j.celrep.2019.04.074. - DOI - PMC - PubMed
Dumont NA, Wang YX, von Maltzahn J, Pasut A, Bentzinger CF, Brun CE, and Rudnicki MA (2015). Dystrophin expression in muscle stem cells regulates their polarity and asymmetric division. Nat. Med. 21, 1455–1463. 10.1038/nm.3990. - DOI - PMC - PubMed
Richie JPJ (1992). The role of glutathione in aging and cancer. Exp. Gerontol. 27, 615–626. 10.1016/0531-5565(92)90015-r. - DOI - PubMed
Haug K, Cochrane K, Nainala VC, Williams M, Chang J, Jayaseelan KV, and O’Donovan C (2020). MetaboLights: a resource evolving in response to the needs of its scientific community. Nucleic Acids Res. 48, D440–D444. 10.1093/nar/gkz1019. - DOI - PMC - PubMed
Edgar R, Domrachev M, and Lash AE (2002). Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 30, 207–210. 10.1093/nar/30.1.207. - DOI - PMC - PubMed
Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, and Gingeras TR (2013). STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21. 10.1093/bioinformatics/bts635. - DOI - PMC - PubMed
Liao Y, Smyth GK, and Shi W (2014). featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923–930. 10.1093/bioinformatics/btt656. - DOI - PubMed
Robinson MD, McCarthy DJ, and Smyth GK (2010). edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140. 10.1093/bioinformatics/btp616. - DOI - PMC - PubMed
Xu T, Park SK, Venable JD, Wohlschlegel JA, Diedrich JK, Cociorva D, Lu B, Liao L, Hewel J, Han X, et al. (2015). ProLuCID: An improved SEQUEST-like algorithm with enhanced sensitivity and specificity. J. Proteomics 129, 16–24. 10.1016/j.jprot.2015.07.001. - DOI - PMC - PubMed
Li X, and Snyder MP (2016). Yeast longevity promoted by reversing aging-associated decline in heavy isotope content. NPJ aging Mech. Dis. 2, 16004. 10.1038/npjamd.2016.4. - DOI - PMC - PubMed
Guan S, Price JC, Prusiner SB, Ghaemmaghami S, and Burlingame AL (2011). A data processing pipeline for mammalian proteome dynamics studies using stable isotope metabolic labeling. Mol. Cell. Proteomics 10, M111.010728. 10.1074/mcp.M111.010728. - DOI - PMC - PubMed
Smith CA, Want EJ, O’Maille G, Abagyan R, and Siuzdak G (2006). XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification. Anal. Chem. 78, 779–787. 10.1021/ac051437y. - DOI - PubMed
Voss B, Hanselmann M, Renard BY, Lindner MS, Köthe U, Kirchner M, and Hamprecht FA (2011). SIMA: simultaneous multiple alignment of LC/MS peak lists. Bioinformatics 27, 987–993. 10.1093/bioinformatics/btr051. - DOI - PubMed
Johnson WE, Li C, and Rabinovic A (2007). Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics 8, 118–127. 10.1093/biostatistics/kxj037. - DOI - PubMed
Wishart DS, Knox C, Guo AC, Eisner R, Young N, Gautam B, Hau DD, Psychogios N, Dong E, Bouatra S, et al. (2009). HMDB: a knowledgebase for the human metabolome. Nucleic Acids Res. 37, D603–10. 10.1093/nar/gkn810. - DOI - PMC - PubMed
Ogata H, Goto S, Sato K, Fujibuchi W, Bono H, and Kanehisa M (1999). KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 27, 29–34. 10.1093/nar/27.1.29. - DOI - PMC - PubMed
Breitling R, Armengaud P, Amtmann A, and Herzyk P (2004). Rank products: a simple, yet powerful, new method to detect differentially regulated genes in replicated microarray experiments. FEBS Lett. 573, 83–92. 10.1016/j.febslet.2004.07.055. - DOI - PubMed
Krueger F, and Andrews SR (2011). Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications. Bioinformatics 27, 1571–1572. 10.1093/bioinformatics/btr167. - DOI - PMC - PubMed
Karolchik D, Hinrichs AS, Furey TS, Roskin KM, Sugnet CW, Haussler D, and Kent WJ (2004). The UCSC Table Browser data retrieval tool. Nucleic Acids Res. 32, D493–6. 10.1093/nar/gkh103. - DOI - PMC - PubMed
Haeussler M, Zweig AS, Tyner C, Speir ML, Rosenbloom KR, Raney BJ, Lee CM, Lee BT, Hinrichs AS, Gonzalez JN, et al. (2019). The UCSC Genome Browser database: 2019 update. Nucleic Acids Res. 47, D853–D858. 10.1093/nar/gky1095. - DOI - PMC - PubMed
Irizarry RA, Ladd-Acosta C, Wen B, Wu Z, Montano C, Onyango P, Cui H, Gabo K, Rongione M, Webster M, et al. (2009). The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat. Genet. 41, 178–186. 10.1038/ng.298. - DOI - PMC - PubMed
Kishore K, de Pretis S, Lister R, Morelli MJ, Bianchi V, Amati B, Ecker JR, and Pelizzola M (2015). methylPipe and compEpiTools: a suite of R packages for the integrative analysis of epigenomics data. BMC Bioinformatics 16, 313. 10.1186/s12859-015-0742-6. - DOI - PMC - PubMed
Ball MP, Li JB, Gao Y, Lee J-H, LeProust EM, Park I-H, Xie B, Daley GQ, and Church GM (2009). Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells. Nat. Biotechnol. 27, 361–368. 10.1038/nbt.1533. - DOI - PMC - PubMed
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, et al. (2005). Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. U. S. A. 102, 15545–15550. 10.1073/pnas.0506580102. - DOI - PMC - PubMed
Hernández-de-Diego R, Tarazona S, Martínez-Mira C, Balzano-Nogueira L, FurióTarí P, Pappas GJJ, and Conesa A (2018). PaintOmics 3: a web resource for the pathway analysis and visualization of multi-omics data. Nucleic Acids Res. 46, W503–W509. 10.1093/nar/gky466. - DOI - PMC - PubMed
García-Alcalde F, García-López F, Dopazo J, and Conesa A (2011). Paintomics: a web based tool for the joint visualization of transcriptomics and metabolomics data. Bioinformatics 27, 137–139. 10.1093/bioinformatics/btq594. - DOI - PMC - PubMed
Varum S, Rodrigues AS, Moura MB, Momcilovic O, Easley CA 4th, Ramalho-Santos J, Van Houten B, and Schatten G (2011). Energy metabolism in human pluripotent stem cells and their differentiated counterparts. PLoS One 6, e20914. 10.1371/journal.pone.0020914. - DOI - PMC - PubMed
Pfaffl MW (2001). A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29, e45. 10.1093/nar/29.9.e45. - DOI - PMC - PubMed
de Morree A, Klein JDD, Gan Q, Farup J, Urtasun A, Kanugovi A, Bilen B, van Velthoven CTJ, Quarta M, and Rando TA (2019). Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function. Science 366, 734–738. 10.1126/science.aax1694. - DOI - PMC - PubMed
Publication types

- - - - -- -- - -
--- --- -   - --- ---