Generation of Human Neurons by microRNA-Mediated Direct Conversion of Dermal Fibroblasts.
Methods Mol Biol
; 2239: 77-100, 2021.
Article
in En
| MEDLINE
| ID: mdl-33226614
ABSTRACT
MicroRNAs (miRNAs), miR-9/9*, and miR-124 (miR-9/9*-124) display fate-reprogramming activities when ectopically expressed in human fibroblasts by erasing the fibroblast identity and evoking a pan-neuronal state. In contrast to induced pluripotent stem cell-derived neurons, miRNA-induced neurons (miNs) retain the biological age of the starting fibroblasts through direct fate conversion and thus provide a human neuron-based platform to study cellular properties inherent in aged neurons and model adult-onset neurodegenerative disorders using patient-derived cells. Furthermore, expression of neuronal subtype-specific transcription factors in conjunction with miR-9/9*-124 guides the miNs to distinct neuronal fates, a feature critical for modeling disorders that affect specific neuronal subtypes. Here, we describe the miR-9/9*-124-based neuronal reprogramming protocols for the generation of several disease-relevant neuronal subtypes striatal medium spiny neurons, cortical neurons, and spinal cord motor neurons.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
MicroRNAs
/
Cellular Reprogramming
/
Neurogenesis
/
Motor Neurons
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Methods Mol Biol
Journal subject:
BIOLOGIA MOLECULAR
Year:
2021
Document type:
Article
Affiliation country:
United States