Single-cell dissection of the human motor and prefrontal cortices in ALS and FTLD.
Cell
; 187(8): 1971-1989.e16, 2024 Apr 11.
Article
em En
| MEDLINE
| ID: mdl-38521060
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Córtex Pré-Frontal
/
Degeneração Lobar Frontotemporal
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Esclerose Lateral Amiotrófica
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2024
Tipo de documento:
Article