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

4 Citations (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

ASJC Scopus subject areas

  • General

Cite this

Hiratsuka, K., Monkawa, T., Akiyama, T., Nakatake, Y., Oda, M., Goparaju, S. K., 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, 9(1), [913]. https://doi.org/10.1038/s41598-018-37485-8