Directed Differentiation of Human Pluripotent Cells to Ureteric Bud Kidney Progenitor-Like Cells

Yun Xia, Emmanuel Nivet, Ignacio Sancho-Martinez, Thomas Gallegos, Keiichiro Suzuki, Daiji Okamura, Min Zu Wu, Ilir Dubova, Concepcion Rodriguez Esteban, Nuria Montserrat, Josep M. Campistol, Juan Carlos Izpisua Belmonte*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

274 Scopus citations

Abstract

Diseases affecting the kidney constitute a major health issue worldwide. Their incidence and poor prognosis affirm the urgent need for the development of new therapeutic strategies. Recently, differentiation of pluripotent cells to somatic lineages has emerged as a promising approach for disease modelling and cell transplantation. Unfortunately, differentiation of pluripotent cells into renal lineages has demonstrated limited success. Here we report on the differentiation of human pluripotent cells into ureteric-bud-committed renal progenitor-like cells. The generated cells demonstrated rapid and specific expression of renal progenitor markers on 4-day exposure to defined media conditions. Further maturation into ureteric bud structures was accomplished on establishment of a three-dimensional culture system in which differentiated human cells assembled and integrated alongside murine cells for the formation of chimeric ureteric buds. Altogether, our results provide a new platform for the study of kidney diseases and lineage commitment, and open new avenues for the future application of regenerative strategies in the clinic.

Original languageEnglish (US)
Pages (from-to)1507-1515
Number of pages9
JournalNature Cell Biology
Volume15
Issue number12
DOIs
StatePublished - Dec 2013
Externally publishedYes

Bibliographical note

Funding Information:
We thank M. Schwarz for administrative support. We thank J. Kasuboski from Waitt Advanced Biophotonics Core at Salk for help with imaging processing. We thank B. C. Lu for his suggestions regarding kidney dissection and organ culture. Y.X. and K.S. were partially supported by the California Institute for Regenerative Medicine. I.S-M. was partially supported by a Nomis Foundation postdoctoral fellowship. Work in the laboratory of J.C.I.B. was supported by grants from Fundacion Cellex, the G. Harold and L. Y. Mathers Charitable Foundation, The Leona M. and Harry B. Helmsley Charitable Trust, IPSEN Foundation, Fundació La Marató de TV3 (121330), CIBER BBN and ISCIII-TERCEL-MINECO.

ASJC Scopus subject areas

  • Cell Biology

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