Cellular and axonal transport phenotypes due to the C9ORF72 HRE in iPSC motor and sensory neurons.
Stem Cell Reports
; 19(7): 957-972, 2024 Jul 09.
Article
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| MEDLINE
| ID: mdl-38876108
ABSTRACT
Induced pluripotent stem cell (iPSC)-derived motor neurons (MNs) from patients with amyotrophic lateral sclerosis (ALS) and the C9ORF72 hexanucleotide repeat expansion (HRE) have multiple cellular phenotypes, but which of these accurately reflect the biology underlying the cell-specific vulnerability of ALS is uncertain. We therefore compared phenotypes due to the C9ORF72 HRE in MNs with sensory neurons (SNs), which are relatively spared in ALS. The iPSC models were able to partially reproduce the differential gene expression seen between adult SNs and MNs. We demonstrated that the typical hallmarks of C9ORF72-ALS, including RNA foci and dipeptide formation, as well as specific axonal transport defects, occurred equally in MNs and SNs, suggesting that these in vitro phenotypes are not sufficient to explain the cell-type selectivity of ALS in isolation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fenotipo
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Células Receptoras Sensoriales
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Transporte Axonal
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Expansión de las Repeticiones de ADN
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Células Madre Pluripotentes Inducidas
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Proteína C9orf72
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Esclerosis Amiotrófica Lateral
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Neuronas Motoras
Límite:
Humans
Idioma:
En
Revista:
Stem Cell Reports
Año:
2024
Tipo del documento:
Article