{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:32:07Z","timestamp":1792787527568,"version":"4.5.0"},"reference-count":74,"publisher":"Wiley","license":[{"start":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T00:00:00Z","timestamp":1574035200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03EB020770"],"award-info":[{"award-number":["R03EB020770"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1652992"],"award-info":[{"award-number":["1652992"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FSU","award":["R03EB020770"],"award-info":[{"award-number":["R03EB020770"]}]},{"name":"FSU","award":["1652992"],"award-info":[{"award-number":["1652992"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Stem Cells International"],"published-print":{"date-parts":[[2019,11,18]]},"abstract":"<jats:p>\n                    Brain spheroids or organoids derived from human pluripotent stem cells (hiPSCs) are still not capable of completely recapitulating\n                    <jats:italic>in vivo<\/jats:italic>\n                    human brain tissue, and one of the limitations is lack of microglia. To add built-in immune function, coculture of the dorsal forebrain spheroids with isogenic microglia-like cells (D-MG) was performed in our study. The three-dimensional D-MG spheroids were analyzed for their transcriptome and compared with isogenic microglia-like cells (MG). Cortical spheroids containing microglia-like cells displayed different metabolic programming, which may affect the associated phenotype. The expression of genes related to glycolysis and hypoxia signaling was increased in cocultured D-MG spheroids, indicating the metabolic shift to aerobic glycolysis, which is in favor of M1 polarization of microglia-like cells. In addition, the metabolic pathways and the signaling pathways involved in cell proliferation, cell death, PIK3\/AKT\/mTOR signaling, eukaryotic initiation factor 2 pathway, and Wnt and Notch pathways were analyzed. The results demonstrate the activation of mTOR and p53 signaling, increased expression of Notch ligands, and the repression of NF-\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B and canonical Wnt pathways, as well as the lower expression of cell cycle genes in the cocultured D-MG spheroids. This analysis indicates that physiological 3-D microenvironment may reshape the immunity of\n                    <jats:italic>in vitro<\/jats:italic>\n                    cortical spheroids and better recapitulate\n                    <jats:italic>in vivo<\/jats:italic>\n                    brain tissue function for disease modeling and drug screening.\n                  <\/jats:p>","DOI":"10.1155\/2019\/2382534","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T18:30:40Z","timestamp":1574101840000},"page":"1-21","source":"Crossref","is-referenced-by-count":36,"title":["Genomics Analysis of Metabolic Pathways of Human Stem Cell-Derived Microglia-Like Cells and the Integrated Cortical Spheroids"],"prefix":"10.1155","volume":"2019","author":[{"given":"Julie","family":"Bejoy","sequence":"first","affiliation":[{"name":"Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuegang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8903-1801","authenticated-orcid":true,"given":"Liqing","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thien","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Jeske","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4720-4671","authenticated-orcid":true,"given":"S\u00e9bastien","family":"Sart","sequence":"additional","affiliation":[{"name":"Hydrodynamics Laboratory (LadHyX)-Department of Mechanics, Ecole Polytechnique, CNRS-UMR7646, 91128 Palaiseau, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Xiang Amy","family":"Sang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, USA"},{"name":"Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida, 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