An alternative pluripotent state confers interspecies chimaeric competency

Jun Wu, Daiji Okamura, Mo Li, Keiichiro Suzuki, Chongyuan Luo, Li Ma, Yupeng He, Zhongwei Li, Chris Benner, Isao Tamura, Marie N. Krause, Joseph R. Nery, Tingting Du, Zhuzhu Zhang, Tomoaki Hishida, Yuta Takahashi, Emi Aizawa, Na Young Kim, Jeronimo Lajara, Pedro GuillenJosep M. Campistol, Concepcion Rodriguez Esteban, Pablo J. Ross, Alan Saghatelian, Bing Ren, Joseph R. Ecker, Juan Carlos Izpisua Belmonte*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

174 Scopus citations


Pluripotency, the ability to generate any cell type of the body, is an evanescent attribute of embryonic cells. Transitory pluripotent cells can be captured at different time points during embryogenesis and maintained as embryonic stem cells or epiblast stem cells in culture. Since ontogenesis is a dynamic process in both space and time, it seems counterintuitive that these two temporal states represent the full spectrum of organismal pluripotency. Here we show that by modulating culture parameters, a stem-cell type with unique spatial characteristics and distinct molecular and functional features, designated as region-selective pluripotent stem cells (rsPSCs), can be efficiently obtained from mouse embryos and primate pluripotent stem cells, including humans. The ease of culturing and editing the genome of human rsPSCs offers advantages for regenerative medicine applications. The unique ability of human rsPSCs to generate post-implantation interspecies chimaeric embryos may facilitate our understanding of early human development and evolution.

Original languageEnglish (US)
Pages (from-to)316-321
Number of pages6
Issue number7552
StatePublished - May 21 2015
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgements We would like to thank S. Mitalipov and J. Thomson for providing rhesusESCs andiPSCs, respectively, F. Gage for providingchimpanzee iPSCs, K. Zhang for assistance with cell line derivation, M. Ku of the H. A. and Mary K. Chapman Charitable Foundations Genomic Sequencing Core for performing RNA-seq and mouse ChIP-seq experiments, M. Chang of the Integrative Genomic and Bioinformatics Core for bioinformatics analysis, W. T. Berggren and the staff of the Salk STEM Core for preparation of custom-mTeSR1 base medium and supply of validated stem culture materials, G. Pao and K. Hasegawa for discussions, Y. Dayn from transgenic core facility and J.Luoforblastocystinjections,Y.Tsunekawafor providingthe mutanteGFPhuman ESCs reporter line, E. O’Connor and K. Marquez of Human Embryonic Stem Cell Core Facility of Sanford Consortium for Regenerative Medicine for FACS sorting, R. H. Benitez, A. Goebl, R. D. Soligalia for assistance with genome editing, M. F. Pera for critical reading of the manuscript, and M. Schwarz, and P. Schwarz for administrative help. M.L. and K.S. are supported by a California Institute for Regenerative Medicine Training Grant. We thank J. L. Mendoza for his support on this project. This work was fundedin part byUCAM (mouse studies). anInvestigator of the Howard Hughes Medical Institute. P.G. was supported by Fundacion Pedro Guillen. Work in the laboratory of J.C.I.B. was supported by G. Harold and Leila Y. Mathers Charitable Foundation, The Leona M. and Harry B. Helmsley Charitable Trust and The Moxie Foundation.

ASJC Scopus subject areas

  • General


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