TY - JOUR
T1 - Induction of human pluripotent stem cells into kidney tissues by synthetic mRNAs encoding transcription factors
AU - Hiratsuka, Ken
AU - Monkawa, Toshiaki
AU - Akiyama, Tomohiko
AU - Nakatake, Yuki
AU - Oda, Mayumi
AU - Goparaju, Sravan Kumar
AU - Kimura, Hiromi
AU - Chikazawa-Nohtomi, Nana
AU - Sato, Saeko
AU - Ishiguro, Keiichiro
AU - Yamaguchi, Shintaro
AU - Suzuki, Sayuri
AU - Morizane, Ryuji
AU - Ko, Shigeru
AU - Itoh, Hiroshi
AU - Ko, Minoru
N1 - Funding Information:
This study was partly supported by the Research Center Network for Realization of Regenerative Medicine, Japan Agency for Medical Research and Development (AMED) (to MSHK); the CREST program from the Japan Science and Technology Agency (JST) (to MSHK); by the Keio University Medical Science Fund – The Mitsunada Sakaguchi Laboratory (to MSHK); Kumamoto university IMEG Joint Research Projects (2017) (to KH); Grant–in-Aid for Research Activity Start-up (23890203, 16H07177) (to RM and KH); Grant-in-Aid for Exploratory Research (26670432) (to HI); Grant-in-Aid for Scientific Research (C) (15K09273) (to TM); Keio Medical Association Research Promotion Fund (2017) (to KH); Keio University Grant-in-Aid for Encouragement of Young Medical Scientists (2016) (to KH); Keio University Grant-in-Aid for Encouragement of Young Medical Scientists (2015) (to KH).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - The derivation of kidney tissues from human pluripotent stem cells (hPSCs) and its application for replacement therapy in end-stage renal disease have been widely discussed. Here we report that consecutive transfections of two sets of synthetic mRNAs encoding transcription factors can induce rapid and efficient differentiation of hPSCs into kidney tissues, termed induced nephron-like organoids (iNephLOs). The first set - FIGLA, PITX2, ASCL1 and TFAP2C, differentiated hPSCs into SIX2+SALL1+ nephron progenitor cells with 92% efficiency within 2 days. Subsequently, the second set - HNF1A, GATA3, GATA1 and EMX2, differentiated these cells into PAX8+LHX1+ pretubular aggregates in another 2 days. Further culture in both 2-dimensional and 3-dimensional conditions produced iNephLOs containing cells characterized as podocytes, proximal tubules, and distal tubules in an additional 10 days. Global gene expression profiles showed similarities between iNephLOs and the human adult kidney, suggesting possible uses of iNephLOs as in vitro models for kidneys.
AB - The derivation of kidney tissues from human pluripotent stem cells (hPSCs) and its application for replacement therapy in end-stage renal disease have been widely discussed. Here we report that consecutive transfections of two sets of synthetic mRNAs encoding transcription factors can induce rapid and efficient differentiation of hPSCs into kidney tissues, termed induced nephron-like organoids (iNephLOs). The first set - FIGLA, PITX2, ASCL1 and TFAP2C, differentiated hPSCs into SIX2+SALL1+ nephron progenitor cells with 92% efficiency within 2 days. Subsequently, the second set - HNF1A, GATA3, GATA1 and EMX2, differentiated these cells into PAX8+LHX1+ pretubular aggregates in another 2 days. Further culture in both 2-dimensional and 3-dimensional conditions produced iNephLOs containing cells characterized as podocytes, proximal tubules, and distal tubules in an additional 10 days. Global gene expression profiles showed similarities between iNephLOs and the human adult kidney, suggesting possible uses of iNephLOs as in vitro models for kidneys.
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U2 - 10.1038/s41598-018-37485-8
DO - 10.1038/s41598-018-37485-8
M3 - Article
C2 - 30696889
AN - SCOPUS:85060766182
SN - 2045-2322
VL - 9
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 913
ER -
