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

doi:10.1038/ncb2872

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 journal › Article › peer-review

278 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 language	English (US)
Pages (from-to)	1507-1515
Number of pages	9
Journal	Nature Cell Biology
Volume	15
Issue number	12
DOIs	https://doi.org/10.1038/ncb2872
State	Published - Dec 2013
Externally published	Yes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ncb2872

Cite this

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title = "Directed Differentiation of Human Pluripotent Cells to Ureteric Bud Kidney Progenitor-Like Cells",

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.",

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

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, Fundaci{\'o} La Marat{\'o} de TV3 (121330), CIBER BBN and ISCIII-TERCEL-MINECO.",

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AU - Suzuki, Keiichiro

AU - Okamura, Daiji

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AU - Dubova, Ilir

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AU - Montserrat, Nuria

AU - Campistol, Josep M.

AU - Izpisua Belmonte, Juan Carlos

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AB - 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.

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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