TY  - JOUR
A1  - Lobentanzer, Sebastian
A1  - Hanin, Geula
A1  - Klein, Jochen
A1  - Soreq, Hermona
T1  - Integrative transcriptomics reveals sexually dimorphic microRNA control of the cholinergic/neurokine interface in schizophrenia and bipolar disorder
T2  - Cell Reports
N2  - RNA sequencing analyses are often limited to identifying lowest p value transcripts, which does not address polygenic phenomena. To overcome this limitation, we developed an integrative approach that combines large-scale transcriptomic meta-analysis of patient brain tissues with single-cell sequencing data of CNS neurons, short RNA sequencing of human male- and female-originating cell lines, and connectomics of transcription factor and microRNA interactions with perturbed transcripts. We used this pipeline to analyze cortical transcripts of schizophrenia and bipolar disorder patients. Although these pathologies show massive transcriptional parallels, their clinically well-known sexual dimorphisms remain unexplained. Our method reveals the differences between afflicted men and women and identifies disease-affected pathways of cholinergic transmission and gp130-family neurokine controllers of immune function interlinked by microRNAs. This approach may open additional perspectives for seeking biomarkers and therapeutic targets in other transmitter systems and diseases.
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/73733
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-737338
SN  - 2211-1247
VL  - 29
IS  - 3
SP  - 764
EP  - 777.e5
PB  - Cell Press
CY  - Maryland Heights, MO
ER  -