Article ; Online: Single-cell dissection of the human motor and prefrontal cortices in ALS and FTLD.
2024 Volume 187, Issue 8, Page(s) 1971–1989.e16
Abstract: Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) share many clinical, pathological, and genetic features, but a detailed understanding of their associated transcriptional alterations across vulnerable cortical cell types ... ...
| Abstract | Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) share many clinical, pathological, and genetic features, but a detailed understanding of their associated transcriptional alterations across vulnerable cortical cell types is lacking. Here, we report a high-resolution, comparative single-cell molecular atlas of the human primary motor and dorsolateral prefrontal cortices and their transcriptional alterations in sporadic and familial ALS and FTLD. By integrating transcriptional and genetic information, we identify known and previously unidentified vulnerable populations in cortical layer 5 and show that ALS- and FTLD-implicated motor and spindle neurons possess a virtually indistinguishable molecular identity. We implicate potential disease mechanisms affecting these cell types as well as non-neuronal drivers of pathogenesis. Finally, we show that neuron loss in cortical layer 5 tracks more closely with transcriptional identity rather than cellular morphology and extends beyond previously reported vulnerable cell types. |
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| MeSH term(s) | Animals ; Humans ; Mice ; Amyotrophic Lateral Sclerosis/genetics ; Amyotrophic Lateral Sclerosis/metabolism ; Amyotrophic Lateral Sclerosis/pathology ; Frontotemporal Dementia/genetics ; Frontotemporal Lobar Degeneration/genetics ; Frontotemporal Lobar Degeneration/metabolism ; Frontotemporal Lobar Degeneration/pathology ; Gene Expression Profiling ; Neurons/metabolism ; Prefrontal Cortex/metabolism ; Prefrontal Cortex/pathology ; Single-Cell Gene Expression Analysis | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2024-03-22 | ||||||||||
| Publishing country | United States | ||||||||||
| Document type | Journal Article | ||||||||||
| ZDB-ID | 187009-9 | ||||||||||
| ISSN | 1097-4172 ; 0092-8674 | ||||||||||
| ISSN (online) | 1097-4172 | ||||||||||
| ISSN | 0092-8674 | ||||||||||
| DOI | 10.1016/j.cell.2024.02.031 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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