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Single\u2010cell RNA\u2010sequencing (scRNA\u2010seq) and assay for transposase\u2010accessible chromatin using sequencing (ATAC\u2010seq) on peripheral blood mononuclear cells from 8 healthy individuals and 8 MDD patients before or after 12 weeks of antidepressant treatment is performed. scRNA\u2010seq analysis reveals a lower proportion of naive T cells, particularly CD4\n                    <jats:sup>+<\/jats:sup>\n                    naive T cells, in MDD patients compared to controls, and in nonresponders versus responders at the baseline. Flow cytometry data analysis of an independent cohort of 35 patients and 40 healthy individuals confirms the findings. Enrichment analysis of differentially expressed genes indicated obvious immune activation in responders. A specific activated CD4\n                    <jats:sup>+<\/jats:sup>\n                    naive T population in responders characterized by enhanced mitogen\u2010activated protein kinases (MAPK)\u00a0pathway is identified. E\u2010twenty six (ETS) is proposed as an upstream regulator of the MAPK pathway and heterogeneous differentiation in activated CD4\n                    <jats:sup>+<\/jats:sup>\n                    naive T population is associated with the response to antidepressant treatment in MDD patients. A distinct immune feature manifested by CD4\n                    <jats:sup>+<\/jats:sup>\n                    naive T cells during antidepressant treatment in MDD is identified. Collectively, this proposes the molecular mechanism that underlies the heterogeneous antidepressant outcomes for MDD.\n                  <\/jats:p>","DOI":"10.1002\/advs.202308393","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T03:35:09Z","timestamp":1718249709000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Integrated Single\u2010Cell RNA\u2010seq and ATAC\u2010seq Reveals Heterogeneous Differentiation of CD4\n                    <sup>+<\/sup>\n                    Naive T Cell Subsets is Associated with Response to Antidepressant Treatment in Major Depressive Disorder"],"prefix":"10.1002","volume":"11","author":[{"given":"Zuoli","family":"Sun","sequence":"first","affiliation":[{"name":"The National Clinical Research Center for Mental Disorders &amp; Beijing Key Laboratory of Mental Disorders Beijing Anding Hospital Capital Medical University  Beijing 100088 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