Induction of human pluripotent stem cells into kidney tissues by synthetic mRNAs encoding transcription factors

Ken Hiratsuka, Toshiaki Monkawa, Tomohiko Akiyama, Yuki Nakatake, Mayumi Oda, Sravan Kumar Goparaju, Hiromi Kimura, Nana Chikazawa-Nohtomi, Saeko Sato, Keiichiro Ishiguro, Shintaro Yamaguchi, Sayuri Suzuki, Ryuji Morizane, Shigeru Ko, Hiroshi Itoh, Minoru Ko

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Article number913
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

Fingerprint

Pluripotent Stem Cells
Organoids
Nephrons
Transcription Factors
Kidney
Messenger RNA
Podocytes
Transcriptome
Chronic Kidney Failure
Transfection
Stem Cells

ASJC Scopus subject areas

  • General

Cite this

Induction of human pluripotent stem cells into kidney tissues by synthetic mRNAs encoding transcription factors. / Hiratsuka, Ken; Monkawa, Toshiaki; Akiyama, Tomohiko; Nakatake, Yuki; Oda, Mayumi; Goparaju, Sravan Kumar; Kimura, Hiromi; Chikazawa-Nohtomi, Nana; Sato, Saeko; Ishiguro, Keiichiro; Yamaguchi, Shintaro; Suzuki, Sayuri; Morizane, Ryuji; Ko, Shigeru; Itoh, Hiroshi; Ko, Minoru.

In: Scientific Reports, Vol. 9, No. 1, 913, 01.12.2019.

Research output: Contribution to journalArticle

Hiratsuka, K, Monkawa, T, Akiyama, T, Nakatake, Y, Oda, M, Goparaju, SK, Kimura, H, Chikazawa-Nohtomi, N, Sato, S, Ishiguro, K, Yamaguchi, S, Suzuki, S, Morizane, R, Ko, S, Itoh, H & Ko, M 2019, 'Induction of human pluripotent stem cells into kidney tissues by synthetic mRNAs encoding transcription factors', Scientific Reports, vol. 9, no. 1, 913. https://doi.org/10.1038/s41598-018-37485-8
Hiratsuka, Ken ; Monkawa, Toshiaki ; Akiyama, Tomohiko ; Nakatake, Yuki ; Oda, Mayumi ; Goparaju, Sravan Kumar ; Kimura, Hiromi ; Chikazawa-Nohtomi, Nana ; Sato, Saeko ; Ishiguro, Keiichiro ; Yamaguchi, Shintaro ; Suzuki, Sayuri ; Morizane, Ryuji ; Ko, Shigeru ; Itoh, Hiroshi ; Ko, Minoru. / Induction of human pluripotent stem cells into kidney tissues by synthetic mRNAs encoding transcription factors. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
@article{5ee4782f174942e186b258ae5dac183c,
title = "Induction of human pluripotent stem cells into kidney tissues by synthetic mRNAs encoding transcription factors",
abstract = "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.",
author = "Ken Hiratsuka and Toshiaki Monkawa and Tomohiko Akiyama and Yuki Nakatake and Mayumi Oda and Goparaju, {Sravan Kumar} and Hiromi Kimura and Nana Chikazawa-Nohtomi and Saeko Sato and Keiichiro Ishiguro and Shintaro Yamaguchi and Sayuri Suzuki and Ryuji Morizane and Shigeru Ko and Hiroshi Itoh and Minoru Ko",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41598-018-37485-8",
language = "English",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=85060766182&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060766182&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-37485-8

DO - 10.1038/s41598-018-37485-8

M3 - Article

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 913

ER -