TY - JOUR
T1 - Controlling the Regional Identity of hPSC-Derived Neurons to Uncover Neuronal Subtype Specificity of Neurological Disease Phenotypes
AU - Imaizumi, Kent
AU - Sone, Takefumi
AU - Ibata, Keiji
AU - Fujimori, Koki
AU - Yuzaki, Michisuke
AU - Akamatsu, Wado
AU - Okano, Hideyuki
N1 - Funding Information:
We are grateful to Y. Okada (Aichi Medical University) and T. Matsumoto (Ajinomoto) for technical assistance, helpful advice, and discussions; T. Abe (Keio University) for statistical analysis; and all members of the H.O. laboratory for encouragement and kind support. We also thank Y. Okada for the HB9-Venus reporter, M. Itakura (Kitasato University) for antibodies, N. Nakatsuji and H. Suemori (Kyoto University) for hESC clones, S. Yamanaka and M. Nakagawa (Kyoto University) for hiPSC clones (253G1 and 201B7), H. Inoue (Kyoto University) for ALS iPSC clones, and N. Suzuki and D. Ito (Keio University) for AD iPSC clones. This work was supported by funding from the Project for the Realization of Regenerative Medicine and Support for Core Institutes for iPS Cell Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT) (to H.O. and W.A.); the Research Center Network for Realization Research Centers/Projects of Regenerative Medicine (the Program for Intractable Disease Research utilizing disease-specific iPS Cells) from the Japan Science and Technology Agency (JST) and the Japan Agency for Medical Research and Development (AMED) (to H.O.); Scientific Research on Innovative Area, a MEXT Grant-in-Aid Project FY2014-2018 “Brain Protein Aging and Dementia Control” (to H.O.); New Energy and Industrial Technology Development Organization (to H.O. and W.A.); and the Keio University Medical Science Fund (to K. Imaizumi). H.O. is a paid scientific advisory board member for SanBio Co., Ltd.
Publisher Copyright:
© 2015 The Authors.
PY - 2015/12/8
Y1 - 2015/12/8
N2 - The CNS contains many diverse neuronal subtypes, and most neurological diseases target specific subtypes. However, the mechanism of neuronal subtype specificity of disease phenotypes remains elusive. Although in vitro disease models employing human pluripotent stem cells (PSCs) have great potential to clarify the association of neuronal subtypes with disease, it is currently difficult to compare various PSC-derived subtypes. This is due to the limited number of subtypes whose induction is established, and different cultivation protocols for each subtype. Here, we report a culture system to control the regional identity of PSC-derived neurons along the anteroposterior (A-P) and dorsoventral (D-V) axes. This system was successfully used to obtain various neuronal subtypes based on the same protocol. Furthermore, we reproduced subtype-specific phenotypes of amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) by comparing the obtained subtypes. Therefore, our culture system provides new opportunities for modeling neurological diseases with PSCs.
AB - The CNS contains many diverse neuronal subtypes, and most neurological diseases target specific subtypes. However, the mechanism of neuronal subtype specificity of disease phenotypes remains elusive. Although in vitro disease models employing human pluripotent stem cells (PSCs) have great potential to clarify the association of neuronal subtypes with disease, it is currently difficult to compare various PSC-derived subtypes. This is due to the limited number of subtypes whose induction is established, and different cultivation protocols for each subtype. Here, we report a culture system to control the regional identity of PSC-derived neurons along the anteroposterior (A-P) and dorsoventral (D-V) axes. This system was successfully used to obtain various neuronal subtypes based on the same protocol. Furthermore, we reproduced subtype-specific phenotypes of amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) by comparing the obtained subtypes. Therefore, our culture system provides new opportunities for modeling neurological diseases with PSCs.
UR - http://www.scopus.com/inward/record.url?scp=84949537366&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84949537366&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2015.10.005
DO - 10.1016/j.stemcr.2015.10.005
M3 - Article
C2 - 26549851
AN - SCOPUS:84949537366
VL - 5
SP - 1010
EP - 1022
JO - Stem Cell Reports
JF - Stem Cell Reports
SN - 2213-6711
IS - 6
ER -