Details

Autor(en) / Beteiligte

• Jaffe, Andrew E
• Hoeppner, Daniel J
• Saito, Takeshi
• Blanpain, Lou
• Ukaigwe, Joy
• Burke, Emily E
• Collado-Torres, Leonardo
• Tao, Ran
• Tajinda, Katsunori
• Maynard, Kristen R
• Tran, Matthew N
• Martinowich, Keri
• Deep-Soboslay, Amy
• Shin, Joo Heon
• Kleinman, Joel E
• Weinberger, Daniel R
• Matsumoto, Mitsuyuki
• Hyde, Thomas M

Titel

Profiling gene expression in the human dentate gyrus granule cell layer reveals insights into schizophrenia and its genetic risk

Ist Teil von

• Nature neuroscience, 2020-04, Vol.23 (4), p.510-519

Ort / Verlag

United States

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• Specific cell populations may have unique contributions to schizophrenia but may be missed in studies of homogenate tissue. Here laser capture microdissection followed by RNA sequencing (LCM-seq) was used to transcriptomically profile the granule cell layer of the dentate gyrus (DG-GCL) in human hippocampus and contrast these data to those obtained from bulk hippocampal homogenate. We identified widespread cell-type-enriched aging and genetic effects in the DG-GCL that were either absent or directionally discordant in bulk hippocampus data. Of the ~9 million expression quantitative trait loci identified in the DG-GCL, 15% were not detected in bulk hippocampus, including 15 schizophrenia risk variants. We created transcriptome-wide association study genetic weights from the DG-GCL, which identified many schizophrenia-associated genetic signals not found in transcriptome-wide association studies from bulk hippocampus, including GRM3 and CACNA1C. These results highlight the improved biological resolution provided by targeted sampling strategies like LCM and complement homogenate and single-nucleus approaches in human brain.