TY - JOUR
T1 - Vasopressin-secreting neurons derived from human embryonic stem cells through specific induction of dorsal hypothalamic progenitors
AU - Ogawa, Koichiro
AU - Suga, Hidetaka
AU - Ozone, Chikafumi
AU - Sakakibara, Mayu
AU - Yamada, Tomiko
AU - Kano, Mayuko
AU - Mitsumoto, Kazuki
AU - Kasai, Takatoshi
AU - Kodani, Yu
AU - Nagasaki, Hiroshi
AU - Yamamoto, Naoki
AU - Hagiwara, Daisuke
AU - Goto, Motomitsu
AU - Banno, Ryoichi
AU - Sugimura, Yoshihisa
AU - Arima, Hiroshi
N1 - Funding Information:
We would like to thank Dr. Yohei Okada (Aichi Medical University) for detailed advice on the coating recipe of dissociation cultures. We are grateful to Akane Yasui for technical support, and to the members of the Arima lab for discussions. This work was supported by grants from Projects for Technological Development (H.S.) of the Research Center Network for Realization of Regenerative Medicine from the Japan Science and Technology Agency (JST) and the Japan Agency for Medical Research and Development (AMED), grants-in-aid for Scientific Research (H.S.) from The Ministry of Education, Culture, Sports, Science and Technology (MEXT), and Nagoya University Hospital Funding for Clinical Research (H.S.).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Arginine-vasopressin (AVP) neurons exist in the hypothalamus, a major region of the diencephalon, and play an essential role in water balance. Here, we established the differentiation method for AVP-secreting neurons from human embryonic stem cells (hESCs) by recapitulating in vitro the in vivo embryonic developmental processes of AVP neurons. At first, the differentiation efficiency was improved. That was achieved through the optimization of the culture condition for obtaining dorsal hypothalamic progenitors. Secondly, the induced AVP neurons were identified by immunohistochemistry and these neurons secreted AVP after potassium chloride stimulation. Additionally, other hypothalamic neuropeptides were also detected, such as oxytocin, corticotropin-releasing hormone, thyrotropin-releasing hormone, pro-opiomelanocortin, agouti-related peptide, orexin, and melanin-concentrating hormone. This is the first report describing the generation of secretory AVP neurons derived from hESCs. This method will be applicable to research using disease models and, potentially, for regenerative medicine of the hypothalamus.
AB - Arginine-vasopressin (AVP) neurons exist in the hypothalamus, a major region of the diencephalon, and play an essential role in water balance. Here, we established the differentiation method for AVP-secreting neurons from human embryonic stem cells (hESCs) by recapitulating in vitro the in vivo embryonic developmental processes of AVP neurons. At first, the differentiation efficiency was improved. That was achieved through the optimization of the culture condition for obtaining dorsal hypothalamic progenitors. Secondly, the induced AVP neurons were identified by immunohistochemistry and these neurons secreted AVP after potassium chloride stimulation. Additionally, other hypothalamic neuropeptides were also detected, such as oxytocin, corticotropin-releasing hormone, thyrotropin-releasing hormone, pro-opiomelanocortin, agouti-related peptide, orexin, and melanin-concentrating hormone. This is the first report describing the generation of secretory AVP neurons derived from hESCs. This method will be applicable to research using disease models and, potentially, for regenerative medicine of the hypothalamus.
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U2 - 10.1038/s41598-018-22053-x
DO - 10.1038/s41598-018-22053-x
M3 - Article
C2 - 29483626
AN - SCOPUS:85042693673
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 3615
ER -