Integrated Single-Cell RNA-seq and ATAC-seq Reveals Heterogeneous Differentiation of CD4 + Naive T Cell Subsets is Associated with Response to Antidepressant Treatment in Major Depressive Disorder.

Autor: Sun Z; The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, China., Zhang B; College of Life Sciences, Beijing Normal University, Beijing, 100875, China., Zhou J; The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, China., Luo Y; The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, China., Zhu X; The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, China., Wang Y; The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, China., He Y; The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, China., Zheng P; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China., Zhang L; The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, China., Yang J; The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, China.; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, 100069, China., Wang G; The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, China.; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, 100069, China.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Aug; Vol. 11 (30), pp. e2308393. Date of Electronic Publication: 2024 Jun 13.
DOI: 10.1002/advs.202308393
Abstrakt: The mechanism involved in major depressive disorder (MDD) is well-studied but the mechanistic origin of the heterogeneous antidepressant effect remains largely unknown. Single-cell RNA-sequencing (scRNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) on peripheral blood mononuclear cells from 8 healthy individuals and 8 MDD patients before or after 12 weeks of antidepressant treatment is performed. scRNA-seq analysis reveals a lower proportion of naive T cells, particularly CD4 + 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 + naive T population in responders characterized by enhanced mitogen-activated protein kinases (MAPK) pathway is identified. E-twenty six (ETS) is proposed as an upstream regulator of the MAPK pathway and heterogeneous differentiation in activated CD4 + naive T population is associated with the response to antidepressant treatment in MDD patients. A distinct immune feature manifested by CD4 + naive T cells during antidepressant treatment in MDD is identified. Collectively, this proposes the molecular mechanism that underlies the heterogeneous antidepressant outcomes for MDD.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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