Induction of human pluripotent stem cells into kidney tissues by synthetic mRNAs encoding transcription factors.
Ken HiratsukaToshiaki MonkawaTomohiko AkiyamaYuhki NakatakeMayumi OdaSravan Kumar GoparajuHiromi KimuraNana Chikazawa-NohtomiSaeko SatoKei-Ichiro IshiguroShintaro YamaguchiSayuri SuzukiRyuji MorizaneShigeru B H KoHiroshi ItohMinoru S H KoPublished in: Scientific reports (2019)
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.
Keyphrases
- pluripotent stem cells
- transcription factor
- endothelial cells
- induced apoptosis
- replacement therapy
- end stage renal disease
- gene expression
- induced pluripotent stem cells
- high glucose
- chronic kidney disease
- cell cycle arrest
- peritoneal dialysis
- oxidative stress
- smoking cessation
- drug induced
- young adults
- nuclear factor
- endoplasmic reticulum stress