التفاصيل البيبلوغرافية
| العنوان: |
Molecular cascades and cell-type specific signatures in ASD revealed by single cell genomics. |
| المؤلفون: |
Wamsley B, Bicks L, Cheng Y, Kawaguchi R, Quintero D, Grundman J, Liu J, Xiao S, Hawken N, Margolis M, Mazariegos S, Geschwind DH |
| المصدر: |
BioRxiv : the preprint server for biology [bioRxiv] 2023 Mar 10. Date of Electronic Publication: 2023 Mar 10. |
| نوع المنشور: |
Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: |
Understanding how genetic variation exerts its effects on the human brain in health and disease has been greatly informed by functional genomic characterization. Studies over the last decade have demonstrated robust evidence of convergent transcriptional and epigenetic profiles in post-mortem cerebral cortex from individuals with Autism Spectrum Disorder (ASD). Here, we perform deep single nuclear (sn) RNAseq to elucidate changes in cell composition, cellular transcriptomes and putative candidate drivers associated with ASD, which we corroborate using snATAC-seq and spatial profiling. We find changes in cell state composition representing transitions from homeostatic to reactive profiles in microglia and astrocytes, a pattern extending to oligodendrocytes and blood brain barrier cells. We identify profound changes in differential expression involving thousands of genes across neuronal and glial subtypes, of which a substantial portion can be accounted for by specific transcription factor networks that are significantly enriched in common and rare genetic risk for ASD. These data, which are available as part of the PsychENCODE consortium, provide robust causal anchors and resultant molecular phenotypes for understanding ASD changes in human brain. |
| التعليقات: |
Update in: Science. 2024 May 24;384(6698):eadh2602. (PMID: 38781372) |
| معلومات مُعتمدة: |
U01 MH115746 United States MH NIMH NIH HHS |
| تواريخ الأحداث: |
Date Created: 20230322 Latest Revision: 20240603 |
| رمز التحديث: |
20240603 |
| مُعرف محوري في PubMed: |
PMC10029000 |
| DOI: |
10.1101/2023.03.10.530869 |
| PMID: |
36945369 |
| قاعدة البيانات: |
MEDLINE |
