{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:29:31Z","timestamp":1792160971030,"version":"4.4.0"},"reference-count":69,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"721","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2023,11,8]]},"abstract":"<jats:p>Inflammation early in life is a clinically established risk factor for autism spectrum disorders and schizophrenia, yet the impact of inflammation on human brain development is poorly understood. The cerebellum undergoes protracted postnatal maturation, making it especially susceptible to perturbations contributing to the risk of developing neurodevelopmental disorders. Here, using single-cell genomics of postmortem cerebellar brain samples, we characterized the postnatal development of cerebellar neurons and glia in 1- to 5-year-old children, comparing individuals who had died while experiencing inflammation with those who had died as a result of an accident. Our analyses revealed that inflammation and postnatal cerebellar maturation are associated with extensive, overlapping transcriptional changes primarily in two subtypes of inhibitory neurons: Purkinje neurons and Golgi neurons. Immunohistochemical analysis of a subset of these postmortem cerebellar samples revealed no change to Purkinje neuron soma size but evidence for increased activation of microglia in those children who had experienced inflammation. Maturation-associated and inflammation-associated gene expression changes included genes implicated in neurodevelopmental disorders. A gene regulatory network model integrating cell type\u2013specific gene expression and chromatin accessibility identified seven temporally specific gene networks in Purkinje neurons and suggested that inflammation may be associated with the premature down-regulation of developmental gene expression programs.<\/jats:p>","DOI":"10.1126\/scitranslmed.ade1283","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T13:59:10Z","timestamp":1697119150000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":31,"title":["A single-cell genomic atlas for maturation of the human cerebellum during early childhood"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6443-7509","authenticated-orcid":true,"given":"Seth A.","family":"Ament","sequence":"first","affiliation":[{"name":"Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA."},{"name":"Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA."},{"name":"UM-MIND, University of Maryland School of Medicine, Baltimore, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia","family":"Cortes-Gutierrez","sequence":"additional","affiliation":[{"name":"Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5910-9647","authenticated-orcid":true,"given":"Brian R.","family":"Herb","sequence":"additional","affiliation":[{"name":"Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA."},{"name":"Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelina","family":"Mocci","sequence":"additional","affiliation":[{"name":"Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA."},{"name":"Department of Pain Sciences, University of Maryland School of Nursing, Baltimore, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6818-6380","authenticated-orcid":true,"given":"Carlo","family":"Colantuoni","sequence":"additional","affiliation":[{"name":"Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA."},{"name":"Departments of Neurology and Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2243-4726","authenticated-orcid":true,"given":"Margaret M.","family":"McCarthy","sequence":"additional","affiliation":[{"name":"UM-MIND, University of Maryland School of Medicine, Baltimore, MD, USA."},{"name":"Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2018.06.008"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aag3194"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/121.4.561"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/123.5.1051"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-019-0152-2"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.08.016"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-018-0952-3"},{"key":"e_1_3_2_9_2","first-page":"123","article-title":"The compartmental restriction of cerebellar interneurons","volume":"6","author":"Giacomo Consalez G.","year":"2013","unstructured":"G. Giacomo Consalez, R. Hawkes, The compartmental restriction of cerebellar interneurons. Front. Neural Circuits 6, 123 (2013).","journal-title":"Front. Neural Circuits"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.189605"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2018.05.013"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04711-3"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-012-0355-9"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.2007.164.4.647"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2008.01.003"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-1350"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2012.08032.x"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1262-16.2016"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-018-0363-8"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00872-y"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.39981"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03220-z"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2021.06.004"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61705-0"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04556-w"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/2040-2392-4-36"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2012.146"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx191"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-014-0141-7"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-37284-1"},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","unstructured":"M. Sepp K. Leiss I. Sarropoulos F. Murat K. Okonechnikov P. Joshi E. Leushkin N. Mbengue C. Schneider J. Schmidt N. Trost L. Sp\u00e4nig P. Giere P. Khaitovich S. Lisgo M. Palkovits L. M. Kutscher S. Anders M. Cardoso-Moreira S. M. Pfister H. Kaessmann Cellular development and evolution of the mammalian cerebellum. bioRxiv 2021.12.20.473443 (2021). https:\/\/doi.org\/10.1101\/2021.12.20.473443.","DOI":"10.1101\/2021.12.20.473443"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01104-0"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature20612"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03145-z"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08186"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00857-4"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3404"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012776"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.267989.115"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-020-01155-1"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00754-9"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1186\/2040-2392-2-5"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.09.017"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03566-5"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01022-8"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nic.2016.03.011"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.155.9.1288"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11310"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12627"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.339"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2019.06.013"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01061-1"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1874-1"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/nargab\/lqaa078"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts040"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4402"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0326-7"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-210491"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4042"},{"key":"e_1_3_2_63_2","doi-asserted-by":"crossref","unstructured":"T. Stuart A. Srivastava C. Lareau R. Satija Multimodal single-cell chromatin analysis with Signac. bioRxiv 2020.11.09.373613 (2020).","DOI":"10.1101\/2020.11.09.373613"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv145"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.06.044"},{"key":"e_1_3_2_67_2","doi-asserted-by":"crossref","unstructured":"F. Wagner Y. Yan I. Yanai K-nearest neighbor smoothing for high-throughput single-cell RNA-Seq data. bioRxiv 10.1101\/217737 (2018). https:\/\/doi.org\/10.1101\/217737.","DOI":"10.1101\/217737"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2019.01.002"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05688-9"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.ade1283","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T13:35:13Z","timestamp":1705412113000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.ade1283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,8]]},"references-count":69,"journal-issue":{"issue":"721","published-print":{"date-parts":[[2023,11,8]]}},"alternative-id":["10.1126\/scitranslmed.ade1283"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.ade1283","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,8]]},"assertion":[{"value":"2022-07-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eade1283"}}