Small molecule-based lineage switch of human adipose-derived stem cells into neural stem cells and functional GABAergic neurons

Jihye Park, Nayeon Lee, Jaekwang Lee, Eun Kyung Choe, Min Kyung Kim, Jeonghoon Lee, Min Soo Byun, Myong Wuk Chon, Seong Who Kim, Changjoon Lee, Ju Han Kim, Jun Soo Kwon, Mi Sook Chang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Cellular reprogramming using small molecules (SMs) without genetic modification provides a promising strategy for generating target cells for cell-based therapy. Human adipose-derived stem cells (hADSCs) are a desirable cell source for clinical application due to their self-renewal capacity, easy obtainability and the lack of safety concerns, such as tumor formation. However, methods to convert hADSCs into neural cells, such as neural stem cells (NSCs), are inefficient, and few if any studies have achieved efficient reprogramming of hADSCs into functional neurons. Here, we developed highly efficient induction protocols to generate NSC-like cells (iNSCs), neuron-like cells (iNs) and GABAergic neuron-like cells (iGNs) from hADSCs via SM-mediated inhibition of SMAD signaling without genetic manipulation. All induced cells adopted morphological, molecular and functional features of their bona fide counterparts. Electrophysiological data demonstrated that iNs and iGNs exhibited electrophysiological properties of neurons and formed neural networks in vitro. Microarray analysis further confirmed that iNSCs and iGNs underwent lineage switch toward a neural fate. Together, these studies provide rapid, reproducible and robust protocols for efficient generation of functional iNSCs, iNs and iGNs from hADSCs, which have utility for modeling disease pathophysiology and providing cell-therapy sources of neurological disorders.

Original languageEnglish
Article number10166
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1
Externally publishedYes

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GABAergic Neurons
Neural Stem Cells
Stem Cells
Cell- and Tissue-Based Therapy
Neurons
Microarray Analysis
Nervous System Diseases
Safety

ASJC Scopus subject areas

  • General

Cite this

Small molecule-based lineage switch of human adipose-derived stem cells into neural stem cells and functional GABAergic neurons. / Park, Jihye; Lee, Nayeon; Lee, Jaekwang; Choe, Eun Kyung; Kim, Min Kyung; Lee, Jeonghoon; Byun, Min Soo; Chon, Myong Wuk; Kim, Seong Who; Lee, Changjoon; Kim, Ju Han; Kwon, Jun Soo; Chang, Mi Sook.

In: Scientific Reports, Vol. 7, No. 1, 10166, 01.12.2017.

Research output: Contribution to journalArticle

Park, J, Lee, N, Lee, J, Choe, EK, Kim, MK, Lee, J, Byun, MS, Chon, MW, Kim, SW, Lee, C, Kim, JH, Kwon, JS & Chang, MS 2017, 'Small molecule-based lineage switch of human adipose-derived stem cells into neural stem cells and functional GABAergic neurons', Scientific Reports, vol. 7, no. 1, 10166. https://doi.org/10.1038/s41598-017-10394-y
Park, Jihye ; Lee, Nayeon ; Lee, Jaekwang ; Choe, Eun Kyung ; Kim, Min Kyung ; Lee, Jeonghoon ; Byun, Min Soo ; Chon, Myong Wuk ; Kim, Seong Who ; Lee, Changjoon ; Kim, Ju Han ; Kwon, Jun Soo ; Chang, Mi Sook. / Small molecule-based lineage switch of human adipose-derived stem cells into neural stem cells and functional GABAergic neurons. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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