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.
authors.affiliation: The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA.
authors.forename: Daiji
authors.initials: D
authors.lastname: Okamura
authors.affiliation: The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA.
authors.forename: Mo
authors.initials: M
authors.lastname: Li
authors.affiliation: The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: 1] Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] The Salk Institute for Biological Studies, Genomic Analysis Laboratory, La Jolla, California 92037, USA.
authors.forename: Chongyuan
authors.initials: C
authors.lastname: Luo
authors.affiliation: The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: The Salk Institute for Biological Studies, Genomic Analysis Laboratory, La Jolla, California 92037, USA.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: He
authors.affiliation: The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: The Salk Institute for Biological Studies, Integrated Genomics, La Jolla, California 92037, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Benner
authors.affiliation: The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA.
authors.forename: Isao
authors.initials: I
authors.lastname: Tamura
authors.affiliation: The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA.
authors.forename: Marie N
authors.initials: MN
authors.lastname: Krause
authors.affiliation: The Salk Institute for Biological Studies, Genomic Analysis Laboratory, La Jolla, California 92037, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Nery
authors.affiliation: Ludwig Institute for Cancer Research, University of California, San Diego School of Medicine, Department of Cellular and Molecular Medicine, 9500 Gilman Drive, La Jolla, California 92093-0653, USA.
authors.forename: Tingting
authors.initials: T
authors.lastname: Du
authors.affiliation: The Salk Institute for Biological Studies, Genomic Analysis Laboratory, La Jolla, California 92037, USA.
authors.forename: Zhuzhu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hishida
authors.affiliation: 1] The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA [2] Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8577, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA.
authors.forename: Emi
authors.initials: E
authors.lastname: Aizawa
authors.affiliation: The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA.
authors.forename: Na Young
authors.initials: NY
authors.lastname: Kim
authors.affiliation: Grado en Medicina, Universidad Católica, San Antonio de Murcia, Campus de los Jerónimos, 135, Guadalupe 30107, Spain.
authors.forename: Jeronimo
authors.initials: J
authors.lastname: Lajara
authors.affiliation: 1] Grado en Medicina, Universidad Católica, San Antonio de Murcia, Campus de los Jerónimos, 135, Guadalupe 30107, Spain [2] Fundacion Pedro Guillen, Clínica Cemtro, Avenida Ventisquero de la Condesa, 42, 28035 Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Guillen
authors.affiliation: Hospital Clinic of Barcelona, Carrer Villarroel, 170, 08036 Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Campistol
authors.affiliation: The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA.
authors.forename: Concepcion Rodriguez
authors.initials: CR
authors.lastname: Esteban
authors.affiliation: University of California, Davis, Davis, California 95616, USA.
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: Ross
authors.affiliation: The Salk Institute for Biological Studies, Peptide Biology Laboratory, La Jolla, California 92037, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Saghatelian
authors.affiliation: Ludwig Institute for Cancer Research, University of California, San Diego School of Medicine, Department of Cellular and Molecular Medicine, 9500 Gilman Drive, La Jolla, California 92093-0653, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Ren
authors.affiliation: 1] Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] The Salk Institute for Biological Studies, Genomic Analysis Laboratory, La Jolla, California 92037, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Ecker
authors.affiliation: The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Izpisua Belmonte
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002460:Cell Line; D002678:Chimera; D053595:Embryonic Stem Cells / Q000166:cytology; D005260:Female; D005855:Germ Layers / Q000166:cytology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D008297:Male; D051379:Mice; D002679:Pan troglodytes; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D044968:Regenerative Medicine; D013045:Species Specificity