Generation of Human Neurons by microRNA-Mediated Direct Conversion of Dermal Fibroblasts

Victoria A. Church, Kitra Cates, Lucia Capano, Shivani Aryal, Woo Kyung Kim, Andrew S. Yoo

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

2 Scopus citations

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.

Original languageEnglish
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages77-100
Number of pages24
DOIs
StatePublished - 2021

Publication series

NameMethods in Molecular Biology
Volume2239
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • Aging
  • Cortical neuron
  • Human neuron
  • Medium spiny neuron
  • Motor neuron
  • Neurogenesis
  • Neuronal cell-fate
  • Neuronal reprogramming
  • miN
  • miRNA-mediated direct conversion

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