Profiling gene expression in the human dentate gyrus granule cell layer reveals insights into schizophrenia and its genetic risk
Jaffe, AE; Hoeppner, DJ; Saito, T; Blanpain, L; Ukaigwe, J; Burke, EE; Collado-Torres, L; Tao, R; Tajinda, K; Maynard, KR; Tran, MN; Martinowich, K; Deep-Soboslay, A; Shin, JH; Kleinman, JE; Weinberger, DR; Matsumoto, M; Hyde, TM
| HERO ID | 7355910 |
|---|---|
| In Press | No |
| Year | 2020 |
| Title | Profiling gene expression in the human dentate gyrus granule cell layer reveals insights into schizophrenia and its genetic risk |
| Authors | Jaffe, AE; Hoeppner, DJ; Saito, T; Blanpain, L; Ukaigwe, J; Burke, EE; Collado-Torres, L; Tao, R; Tajinda, K; Maynard, KR; Tran, MN; Martinowich, K; Deep-Soboslay, A; Shin, JH; Kleinman, JE; Weinberger, DR; Matsumoto, M; Hyde, TM |
| Journal | Nature Neuroscience |
| Volume | 23 |
| Issue | 4 |
| Page Numbers | 510-519 |
| Abstract | 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. |
| Doi | 10.1038/s41593-020-0604-z |
| Pmid | 32203495 |
| Wosid | WOS:000519843200001 |
| Url | http://www.nature.com/articles/s41593-020-0604-z |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |