Induction of human pluripotent stem cells into kidney tissues by synthetic mRNAs
encoding transcription factors.
Authors 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
SBH, Itoh H, Ko MSH
Submitted By Submitted Externally on 5/13/2019
Status Published
Journal Scientific reports
Year 2019
Date Published 1/1/2019
Volume : Pages 9 : 913
PubMed Reference 30696889
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.

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