A combination of small molecules directly reprograms mouse fibroblasts into neural stem cells

Jie Zheng, Kyung Ah Choi, Phil Jun Kang, Solji Hyeon, Suhyun Kwon, Jai Hee Moon, Insik Hwang, Yang In Kim, Yoon Sik Kim, Byung Sun Yoon, Gyuman Park, Jang Bo Lee, Sunghoi Hong, Seungkwon You

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The generation of induced neural stem cells (iNSCs) from somatic cells using defined factors provides new avenues for basic research and cell therapies for various neurological diseases, such as Parkinson's disease, Huntington's disease, and spinal cord injuries. However, the transcription factors used for direct reprogramming have the potential to cause unexpected genetic modifications, which limits their potential application in cell therapies. Here, we show that a combination of four chemical compounds resulted in cells directly acquiring a NSC identity; we termed these cells chemically-induced NSCs (ciNSCs). ciNSCs expressed NSC markers (Pax6, PLZF, Nestin, Sox2, and Sox1) and resembled NSCs in terms of their morphology, self-renewal, gene expression profile, and electrophysiological function when differentiated into the neuronal lineage. Moreover, ciNSCs could differentiate into several types of mature neurons (dopaminergic, GABAergic, and cholinergic) as well as astrocytes and oligodendrocytes in vitro. Taken together, our results suggest that stably expandable and functional ciNSCs can be directly reprogrammed from mouse fibroblasts using a combination of small molecules without any genetic manipulation, and will provide a new source of cells for cellular replacement therapy of neurodegenerative diseases.

Original languageEnglish
Pages (from-to)42-48
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume476
Issue number1
DOIs
Publication statusPublished - 2016 Jul 15

Fingerprint

Neural Stem Cells
Fibroblasts
Stem cells
Molecules
Cell- and Tissue-Based Therapy
Neurodegenerative diseases
Nestin
Chemical compounds
Gene expression
GABAergic Neurons
Cholinergic Agents
Neurons
Cholinergic Neurons
Dopaminergic Neurons
Huntington Disease
Oligodendroglia
Transcription Factors
Spinal Cord Injuries
Transcriptome
Astrocytes

Keywords

  • Lineage conversion
  • Neural stem cell
  • Reprogramming
  • Small molecules

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

A combination of small molecules directly reprograms mouse fibroblasts into neural stem cells. / Zheng, Jie; Choi, Kyung Ah; Kang, Phil Jun; Hyeon, Solji; Kwon, Suhyun; Moon, Jai Hee; Hwang, Insik; Kim, Yang In; Kim, Yoon Sik; Yoon, Byung Sun; Park, Gyuman; Lee, Jang Bo; Hong, Sunghoi; You, Seungkwon.

In: Biochemical and Biophysical Research Communications, Vol. 476, No. 1, 15.07.2016, p. 42-48.

Research output: Contribution to journalArticle

Zheng, Jie ; Choi, Kyung Ah ; Kang, Phil Jun ; Hyeon, Solji ; Kwon, Suhyun ; Moon, Jai Hee ; Hwang, Insik ; Kim, Yang In ; Kim, Yoon Sik ; Yoon, Byung Sun ; Park, Gyuman ; Lee, Jang Bo ; Hong, Sunghoi ; You, Seungkwon. / A combination of small molecules directly reprograms mouse fibroblasts into neural stem cells. In: Biochemical and Biophysical Research Communications. 2016 ; Vol. 476, No. 1. pp. 42-48.
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