{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T13:57:20Z","timestamp":1783605440979,"version":"3.55.0"},"reference-count":78,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T00:00:00Z","timestamp":1771113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Macau Start-Up research","award":["SRG 2024-00013-FHS"],"award-info":[{"award-number":["SRG 2024-00013-FHS"]}]},{"DOI":"10.13039\/501100006469","name":"Macao Science and Technology Development Fund","doi-asserted-by":"crossref","award":["0113\/2024\/R1A2"],"award-info":[{"award-number":["0113\/2024\/R1A2"]}],"id":[{"id":"10.13039\/501100006469","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Stem cells maintain tissue homeostasis through precisely regulated self-renewal and differentiation, processes largely dependent on metabolic control. The Drosophila testis provides an ideal model system to study metabolism regulation of stem cell homeostasis due to many advantages, including its well-defined stem cell niche architecture and genetic tractability. Recent studies have revealed that germline stem cells (GSCs) and somatic cyst stem cells (CySCs) exhibit distinct metabolic profiles. In particular, GSCs exhibit a metabolic feature closely associated with mitochondrial dynamics, lipid metabolism, and redox homeostasis, all of which are essential for maintaining their stem identity through the regulation of TOR (Target of Rapamycin) signaling. Nutrient sensing through the insulin\/TOR, BMP, and JAK-STAT pathways integrates nutritional cues with developmental programs. Lipid metabolism and membrane homeostasis further contribute to the maintenance of stem cells. Metabolic intermediates function as signaling molecules, modulating niche-stem cell interactions and epigenetic modifications in stem cells. Hence, dysregulation of metabolic homeostasis can lead to stem cell depletion and age-related reproductive decline. This review synthesizes the current understanding of metabolic regulation in Drosophila testis stem cell maintenance, identifies critical knowledge gaps, and explores future research directions such as spatial\/temporal metabolomics approaches. Lastly, we highlight how these insights may help understand mammalian stem cell biology and regenerative medicine.<\/jats:p>","DOI":"10.3390\/ijms27041884","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T10:14:32Z","timestamp":1771236872000},"page":"1884","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metabolic Regulation in the Maintenance of Drosophila Testis Stem Cells"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5315-0395","authenticated-orcid":false,"given":"Jiao","family":"Liu","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences, University of Macau, Taipa, Macau 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1089-2104","authenticated-orcid":false,"given":"Peixin","family":"Xu","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, University of Macau, Taipa, Macau 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichen","family":"Liu","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, University of Macau, Taipa, Macau 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuke","family":"Xie","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, University of Macau, Taipa, Macau 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, University of Macau, Taipa, Macau 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyeong Hun","family":"Baeg","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, University of Macau, Taipa, Macau 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1089\/ars.2020.8126","article-title":"Metabolic Regulation of Stem Cells and Differentiation: A Forkhead Box O Transcription Factor Perspective","volume":"34","author":"Ludikhuize","year":"2021","journal-title":"Antioxid. Redox Signal."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/joim.12247","article-title":"Metabolic regulation of stem cell function","volume":"276","author":"Burgess","year":"2014","journal-title":"J. Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lange, C., and Bifari, F. (2020). Editorial: Metabolic Regulation of Stem Cells and Tissue Growth. Front. Mol. Neurosci., 13.","DOI":"10.3389\/fnmol.2020.625606"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1242\/dev.056242","article-title":"The stem cell niche: Lessons from the Drosophila testis","volume":"138","author":"Matunis","year":"2011","journal-title":"Development"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"137","DOI":"10.4161\/spmg.21763","article-title":"Recent advances in Drosophila male germline stem cell biology","volume":"2","author":"Matunis","year":"2012","journal-title":"Spermatogenesis"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.ymeth.2014.04.020","article-title":"Investigating spermatogenesis in Drosophila melanogaster","volume":"68","author":"Demarco","year":"2014","journal-title":"Methods"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Xie, T. (2008). Germline stem cell niches. StemBook, Harvard Stem Cell Institute.","DOI":"10.3824\/stembook.1.23.1"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1016\/j.stem.2022.10.008","article-title":"Spatial dynamic metabolomics identifies metabolic cell fate trajectories in human kidney differentiation","volume":"29","author":"Wang","year":"2022","journal-title":"Cell Stem Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1247\/csf.08042","article-title":"Male germline stem cell division and spermatocyte growth require insulin signaling in Drosophila","volume":"34","author":"Ueishi","year":"2009","journal-title":"Cell Struct. Funct."},{"key":"ref_10","unstructured":"de la Maza, D.S., Jefferson, H., Brucker, C.I., Paoli, S., and Amoyel, M. (2025). Somatic cells compartmentalise their metabolism to sustain germ cell survival. bioRxiv, preprint."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Vedelek, V., Bodai, L., Gr\u00e9zal, G., Kov\u00e1cs, B., Boros, I.M., Laurinyecz, B., and Sinka, R. (2018). Analysis of Drosophila melanogaster testis transcriptome. BMC Genom., 19.","DOI":"10.1186\/s12864-018-5085-z"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tiwari, S.K., and Mandal, S. (2021). Mitochondrial Control of Stem Cell State and Fate: Lessons from Drosophila. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.606639"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"RP90509","DOI":"10.7554\/eLife.90509","article-title":"Chromatin and gene expression changes during female Drosophila germline stem cell development illuminate the biology of highly potent stem cells","volume":"12","author":"Pang","year":"2023","journal-title":"Elife"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1262\/jrd.2021-137","article-title":"Metabolic pathways regulating the development and non-genomic heritable traits of germ cells","volume":"68","author":"Matsui","year":"2022","journal-title":"J. Reprod. Dev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1210\/er.2014-1101","article-title":"The Mammalian Blood-Testis Barrier: Its Biology and Regulation","volume":"36","author":"Mruk","year":"2015","journal-title":"Endocr. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/j.1440-169X.2010.01174.x","article-title":"Stem cells in mammalian spermatogenesis","volume":"52","author":"Yoshida","year":"2010","journal-title":"Dev. Growth Differ."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.molcel.2008.04.009","article-title":"Oxygen sensing by metazoans: The central role of the HIF hydroxylase pathway","volume":"30","author":"Kaelin","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1056\/NEJMra1011165","article-title":"Oxygen sensing, homeostasis, and disease","volume":"365","author":"Semenza","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.jphs.2025.05.017","article-title":"HIF-1\u03b1 stabilization in osteoclasts induces the expression of aerobic glycolysis-related proteins GLUT1, LDHA, and MCT4","volume":"158","author":"Nishioku","year":"2025","journal-title":"J. Pharmacol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Handke, B., Poernbacher, I., Goetze, S., Ahrens, C.H., Omasits, U., Marty, F., Simigdala, N., Meyer, I., Wollscheid, B., and Brunner, E. (2013). The hemolymph proteome of fed and starved Drosophila larvae. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067208"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1534\/genetics.117.300167","article-title":"Development and Function of the Drosophila Tracheal System","volume":"209","author":"Hayashi","year":"2018","journal-title":"Genetics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.devcel.2014.01.020","article-title":"A regulatory network of Drosophila germline stem cell self-renewal","volume":"28","author":"Yan","year":"2014","journal-title":"Dev. Cell"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Hof-Michel, S., and B\u00f6kel, C. (2020). Transcriptome analysis of somatic cell populations in the Drosophila testis links metabolism and stemness. bioRxiv, preprint.","DOI":"10.1101\/2020.02.24.962639"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Vachias, C., Tourlonias, C., Grel\u00e9e, L., Gueguen, N., Renaud, Y., Venugopal, P., Richard, G., Pouchin, P., Brasset, E., and Mirouse, V. (2025). Gap junctions allow transfer of metabolites between germ cells and somatic cells to promote germ cell growth in the Drosophila ovary. PLoS Biol., 23.","DOI":"10.1371\/journal.pbio.3003045"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.cmet.2017.04.019","article-title":"Metabolic Teamwork in the Stem Cell Niche","volume":"25","author":"Roper","year":"2017","journal-title":"Cell Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"19695","DOI":"10.1038\/s41598-019-55728-0","article-title":"Mitochondrial fission regulates germ cell differentiation by suppressing ROS-mediated activation of Epidermal Growth Factor Signaling in the Drosophila larval testis","volume":"9","author":"Jones","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e13191","DOI":"10.1111\/acel.13191","article-title":"Aging shifts mitochondrial dynamics toward fission to promote germline stem cell loss","volume":"19","author":"Amartuvshin","year":"2020","journal-title":"Aging Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1111\/j.1474-9726.2006.00221.x","article-title":"Dynamics of the male germline stem cell population during aging of Drosophila melanogaster","volume":"5","author":"Wallenfang","year":"2006","journal-title":"Aging Cell"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sinenko, S.A., Starkova, T.Y., Kuzmin, A.A., and Tomilin, A.N. (2021). Physiological Signaling Functions of Reactive Oxygen Species in Stem Cells: From Flies to Man. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.714370"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.redox.2017.12.002","article-title":"Small Maf functions in the maintenance of germline stem cells in the Drosophila testis","volume":"15","author":"Tan","year":"2018","journal-title":"Redox Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.tibs.2010.04.002","article-title":"Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes","volume":"35","author":"Hamanaka","year":"2010","journal-title":"Trends Biochem. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"jcs235937","DOI":"10.1242\/jcs.235937","article-title":"Mitochondrial dynamics during spermatogenesis","volume":"133","author":"Varuzhanyan","year":"2020","journal-title":"J. Cell Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1242\/dev.01881","article-title":"Histone deacetylase 1 regulates retinal neurogenesis in zebrafish by suppressing Wnt and Notch signaling pathways","volume":"132","author":"Yamaguchi","year":"2005","journal-title":"Development"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1747-1028-1-29","article-title":"Regulation of germline stem cell proliferation downstream of nutrient sensing","volume":"1","author":"Narbonne","year":"2006","journal-title":"Cell Div."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.ydbio.2010.11.032","article-title":"Insulin signals control the competence of the Drosophila female germline stem cell niche to respond to Notch ligands","volume":"350","author":"Hsu","year":"2011","journal-title":"Dev. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3914","DOI":"10.1242\/dev.139782","article-title":"Somatic stem cell differentiation is regulated by PI3K\/Tor signaling in response to local cues","volume":"143","author":"Amoyel","year":"2016","journal-title":"Development"},{"key":"ref_37","first-page":"1101-1116.e1105","article-title":"EGFR Signaling Stimulates Autophagy to Regulate Stem Cell Maintenance and Lipid Homeostasis in the Drosophila Testis","volume":"30","author":"Uyemura","year":"2020","journal-title":"Cell Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12929-020-00679-2","article-title":"Amino acid-dependent control of mTORC1 signaling: A variety of regulatory modes","volume":"27","author":"Takahara","year":"2020","journal-title":"J. Biomed. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Parisi, F., Riccardo, S., Daniel, M., Saqcena, M., Kundu, N., Pession, A., Grifoni, D., Stocker, H., Tabak, E., and Bellosta, P. (2011). Drosophila insulin and target of rapamycin (TOR) pathways regulate GSK3 beta activity to control Myc stability and determine Myc expression in vivo. BMC Biol., 9.","DOI":"10.1186\/1741-7007-9-65"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.stem.2024.01.003","article-title":"Metabolic regulation of the hallmarks of stem cell biology","volume":"31","author":"Jackson","year":"2024","journal-title":"Cell Stem Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.stem.2021.02.016","article-title":"Challenges in Studying Stem Cell Metabolism","volume":"28","author":"Christofk","year":"2021","journal-title":"Cell Stem Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1242\/dev.01025","article-title":"Gbb\/Bmp signaling is essential for maintaining germline stem cells and for repressing bam transcription in the Drosophila testis","volume":"131","author":"Kawase","year":"2004","journal-title":"Development"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/ncomms1426","article-title":"Local BMP receptor activation at adherens junctions in the Drosophila germline stem cell niche","volume":"2","author":"Michel","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s42977-022-00122-7","article-title":"Autophagy is required for spermatogonial differentiation in the Drosophila testis","volume":"73","author":"Varga","year":"2022","journal-title":"Biol. Futur."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Cl\u00e9mot, M., D\u2019Alterio, C., Kwang, A.C., and Jones, D.L. (2024). mTORC1 is required for differentiation of germline stem cells in the Drosophila melanogaster testis. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0300337"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4224","DOI":"10.1128\/MCB.00363-10","article-title":"Cross talk between insulin and bone morphogenetic protein signaling systems in brown adipogenesis","volume":"30","author":"Zhang","year":"2010","journal-title":"Mol. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e75023","DOI":"10.7554\/eLife.75023","article-title":"Transcriptional regulation of cyclophilin D by BMP\/Smad signaling and its role in osteogenic differentiation","volume":"11","author":"Sautchuk","year":"2022","journal-title":"Elife"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.cub.2012.01.056","article-title":"The niche-dependent feedback loop generates a BMP activity gradient to determine the germline stem cell fate","volume":"22","author":"Xia","year":"2012","journal-title":"Curr. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Sinha, N., van Schothorst, E.M., Hooiveld, G., Keijer, J., Martins Dos Santos, V.A.P., and Suarez-Diez, M. (2021). Exploring the associations between transcript levels and fluxes in constraint-based models of metabolism. BMC Bioinform., 22.","DOI":"10.1186\/s12859-021-04488-8"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ydbio.2012.09.009","article-title":"Jak-STAT regulation of cyst stem cell development in the Drosophila testis","volume":"372","author":"Sinden","year":"2012","journal-title":"Dev. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6766","DOI":"10.1038\/s41467-025-62046-9","article-title":"Dissecting the enhancer gene regulatory network in early Drosophila spermatogenesis","volume":"16","author":"Sekhar","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.cub.2018.11.064","article-title":"Diminished Jak\/STAT Signaling Causes Early-Onset Aging Defects in Stem Cell Cytokinesis","volume":"29","author":"Lenhart","year":"2019","journal-title":"Curr. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e13648","DOI":"10.1111\/cpr.13648","article-title":"A regulatory loop of JAK\/STAT signalling and its downstream targets represses cell fate conversion and maintains male germline stem cell niche homeostasis","volume":"57","author":"Kong","year":"2024","journal-title":"Cell Prolif."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Amoyel, M., Anderson, J., Suisse, A., Glasner, J., and Bach, E.A. (2016). Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1005815"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"dev167643","DOI":"10.1242\/dev.167643","article-title":"JAK\/STAT signaling in stem cells and regeneration: From Drosophila to vertebrates","volume":"146","author":"Herrera","year":"2019","journal-title":"Development"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.immuni.2014.12.023","article-title":"Macrophage-derived upd3 cytokine causes impaired glucose homeostasis and reduced lifespan in Drosophila fed a lipid-rich diet","volume":"42","author":"Woodcock","year":"2015","journal-title":"Immunity"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e51595","DOI":"10.7554\/eLife.51595","article-title":"Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila","volume":"9","author":"Kierdorf","year":"2020","journal-title":"Elife"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/s12964-024-01575-0","article-title":"JAK\/STAT mediated insulin resistance in muscles is essential for effective immune response","volume":"22","author":"McMullen","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"15713","DOI":"10.1038\/s41598-017-15940-2","article-title":"Drosophila muscles regulate the immune response against wasp infection via carbohydrate metabolism","volume":"7","author":"Yang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"16369","DOI":"10.1038\/s41598-017-16638-1","article-title":"Drosophila Kruppel homolog 1 represses lipolysis through interaction with dFOXO","volume":"7","author":"Kang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Jiang, Y., Yan, F., Feng, Z., Lazarovici, P., and Zheng, W. (2019). Signaling Network of Forkhead Family of Transcription Factors (FOXO) in Dietary Restriction. Cells, 9.","DOI":"10.3390\/cells9010100"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"9117","DOI":"10.1128\/MCB.23.24.9117-9126.2003","article-title":"Signaling from Akt to FRAP\/TOR targets both 4E-BP and S6K in Drosophila melanogaster","volume":"23","author":"Miron","year":"2003","journal-title":"Mol. Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1021\/acs.jproteome.4c00646","article-title":"Recent Developments in Single-Cell Metabolomics by Mass Spectrometry\u2500A Perspective","volume":"24","author":"Petrova","year":"2025","journal-title":"J. Proteome Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1021\/jasms.0c00439","article-title":"Spatially Resolved Mass Spectrometry at the Single Cell: Recent Innovations in Proteomics and Metabolomics","volume":"32","author":"Taylor","year":"2021","journal-title":"J. Am. Soc. Mass. Spectrom."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.cmet.2023.12.005","article-title":"Deciphering the metabolic heterogeneity of hematopoietic stem cells with single-cell resolution","volume":"36","author":"Cao","year":"2024","journal-title":"Cell Metab."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.copbio.2021.07.015","article-title":"The limitless applications of single-cell metabolomics","volume":"71","author":"Guo","year":"2021","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"szaf037","DOI":"10.1093\/stcltm\/szaf037","article-title":"Artificial intelligence and systems biology analysis in stem cell research and therapeutics development","volume":"14","author":"Hinterseher","year":"2025","journal-title":"Stem Cells Transl. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/s41467-025-55825-x","article-title":"Mitochondrial segmentation and function prediction in live-cell images with deep learning","volume":"16","author":"Ding","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_69","first-page":"100379","article-title":"Integrating transcriptomic data with metabolic model unravels the electron transfer mechanisms of Methanosarcina barkeri","volume":"28","author":"Tang","year":"2025","journal-title":"Water Res. X"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Steach, H., Viswanath, S., He, Y., Zhang, X., Ivanova, N., Hirn, M., Perlmutter, M., and Krishnaswamy, S. (2023). Inferring Metabolic States from Single Cell Transcriptomic Data via Geometric Deep Learning. bioRxiv, preprint.","DOI":"10.1101\/2023.12.05.570153"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"016112","DOI":"10.1063\/5.0188476","article-title":"3D convolutional neural networks predict cellular metabolic pathway use from fluorescence lifetime decay data","volume":"8","author":"Hu","year":"2024","journal-title":"APL Bioeng."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"15760","DOI":"10.1038\/s41598-024-66591-z","article-title":"Noninvasive, label-free image approaches to predict multimodal molecular markers in pluripotency assessment","volume":"14","author":"Akiyoshi","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"27436","DOI":"10.1038\/s41598-025-09846-7","article-title":"Creating interpretable deep learning models to identify species using environmental DNA sequences","volume":"15","author":"Waggoner","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Kalleberg, J., Rissman, J., and Schnabel, R.D. (2024). Overcoming Limitations to Deep Learning in Domesticated Animals with TrioTrain. bioRxiv, preprint.","DOI":"10.1101\/2024.04.15.589602"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/s41586-023-06139-9","article-title":"Transfer learning enables predictions in network biology","volume":"618","author":"Theodoris","year":"2023","journal-title":"Nature"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Pan, L., Gao, Q., Wei, K., Yu, Y., Qin, G., and Wang, T. (2025). A robust transfer learning approach for high-dimensional linear regression to support integration of multi-source gene expression data. PLoS Comput. Biol., 21.","DOI":"10.1371\/journal.pcbi.1012739"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"110774","DOI":"10.1016\/j.celrep.2022.110774","article-title":"Cell-cycle exit and stem cell differentiation are coupled through regulation of mitochondrial activity in the Drosophila testis","volume":"39","author":"Phillimore","year":"2022","journal-title":"Cell Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1038\/s41556-019-0332-3","article-title":"Mitochondrial fusion regulates lipid homeostasis and stem cell maintenance in the Drosophila testis","volume":"21","author":"Uyemura","year":"2019","journal-title":"Nat. Cell Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/4\/1884\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T05:12:31Z","timestamp":1771305151000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/4\/1884"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,15]]},"references-count":78,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27041884"],"URL":"https:\/\/doi.org\/10.3390\/ijms27041884","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,15]]}}}