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 Guillen; Josep M. Campistol; Concepcion Rodriguez Esteban; Pablo J. Ross; Alan Saghatelian; Bing Ren; Joseph R. Ecker; Juan Carlos Izpisua Belmonte

doi:10.1038/nature14413

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 journal › Article › peer-review

194 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	316-321
Number of pages	6
Journal	NATURE
Volume	521
Issue number	7552
DOIs	https://doi.org/10.1038/nature14413
State	Published - May 21 2015
Externally published	Yes

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). J.R.E.is 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

UN SDGs

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

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10.1038/nature14413

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Wu, J., Okamura, D., Li, M., Suzuki, K., Luo, C., Ma, L., He, Y., Li, Z., Benner, C., Tamura, I., Krause, M. N., Nery, J. R., Du, T., Zhang, Z., Hishida, T., Takahashi, Y., Aizawa, E., Kim, N. Y., Lajara, J., ... Belmonte, J. C. I. (2015). An alternative pluripotent state confers interspecies chimaeric competency. NATURE, 521(7552), 316-321. https://doi.org/10.1038/nature14413

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title = "An alternative pluripotent state confers interspecies chimaeric competency",

abstract = "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.",

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

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{\textquoteright}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). J.R.E.is 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.",

year = "2015",

month = may,

day = "21",

doi = "10.1038/nature14413",

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Wu, J, Okamura, D, Li, M, Suzuki, K, Luo, C, Ma, L, He, Y, Li, Z, Benner, C, Tamura, I, Krause, MN, Nery, JR, Du, T, Zhang, Z, Hishida, T, Takahashi, Y, Aizawa, E, Kim, NY, Lajara, J, Guillen, P, Campistol, JM, Esteban, CR, Ross, PJ, Saghatelian, A, Ren, B, Ecker, JR & Belmonte, JCI 2015, 'An alternative pluripotent state confers interspecies chimaeric competency', NATURE, vol. 521, no. 7552, pp. 316-321. https://doi.org/10.1038/nature14413

TY - JOUR

T1 - An alternative pluripotent state confers interspecies chimaeric competency

AU - Wu, Jun

AU - Okamura, Daiji

AU - Li, Mo

AU - Suzuki, Keiichiro

AU - Luo, Chongyuan

AU - Ma, Li

AU - He, Yupeng

AU - Li, Zhongwei

AU - Benner, Chris

AU - Tamura, Isao

AU - Krause, Marie N.

AU - Nery, Joseph R.

AU - Du, Tingting

AU - Zhang, Zhuzhu

AU - Hishida, Tomoaki

AU - Takahashi, Yuta

AU - Aizawa, Emi

AU - Kim, Na Young

AU - Lajara, Jeronimo

AU - Guillen, Pedro

AU - Campistol, Josep M.

AU - Esteban, Concepcion Rodriguez

AU - Ross, Pablo J.

AU - Saghatelian, Alan

AU - Ren, Bing

AU - Ecker, Joseph R.

AU - Belmonte, Juan Carlos Izpisua

N1 - 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). J.R.E.is 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.

PY - 2015/5/21

Y1 - 2015/5/21

N2 - 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.

AB - 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.

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DO - 10.1038/nature14413

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SN - 0028-0836

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SP - 316

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JO - NATURE

JF - NATURE

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ER -

An alternative pluripotent state confers interspecies chimaeric competency

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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