TY - JOUR
T1 - A combination of small molecules directly reprograms mouse fibroblasts into neural stem cells
AU - Zheng, Jie
AU - Choi, Kyung Ah
AU - Kang, Phil Jun
AU - Hyeon, Solji
AU - Kwon, Suhyun
AU - Moon, Jai Hee
AU - Hwang, Insik
AU - Kim, Yang In
AU - Kim, Yoon Sik
AU - Yoon, Byung Sun
AU - Park, Gyuman
AU - Lee, Jangbo
AU - Hong, Sunghoi
AU - You, Seungkwon
N1 - Funding Information:
This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation of Korea funded by the Korean Ministry of Science, ICT & Future Planning (MSIP) NRF-2010-0020347 , NRF-2014M3A9D3034158 and NRF-2012M3A9C6050131 , a grant of the Korea Health Technology R&D Project , Ministry of Health & Welfare Grant A120392 , A12039212010000300 and School of Life Sciences and Biotechnology for BK21 PLUS, Korea University.
Publisher Copyright:
© 2016 Published by Elsevier Inc.
PY - 2016/7/15
Y1 - 2016/7/15
N2 - 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.
AB - 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.
KW - Lineage conversion
KW - Neural stem cell
KW - Reprogramming
KW - Small molecules
UR - http://www.scopus.com/inward/record.url?scp=84970028617&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2016.05.080
DO - 10.1016/j.bbrc.2016.05.080
M3 - Article
C2 - 27207831
AN - SCOPUS:84970028617
SN - 0006-291X
VL - 476
SP - 42
EP - 48
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -