An alternative pluripotent state confers interspecies chimaeric competency

• Published in: Nature (London) Vol. 521; no. 7552; pp. 316 - 321
• Main Authors: Wu, Jun, Okamura, Daiji, Li, Mo, Suzuki, Keiichiro, Luo, Chongyuan, Ma, Li, He, Yupeng, Li, Zhongwei, Benner, Chris, Tamura, Isao, Krause, Marie N., Nery, Joseph R., Du, Tingting, Zhang, Zhuzhu, Hishida, Tomoaki, Takahashi, Yuta, Aizawa, Emi, Kim, Na Young, Lajara, Jeronimo, Guillen, Pedro, Campistol, Josep M., Esteban, Concepcion Rodriguez, Ross, Pablo J., Saghatelian, Alan, Ren, Bing, Ecker, Joseph R., Belmonte, Juan Carlos Izpisua
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.05.2015; Nature Publishing Group
• Subjects: 631/532/2064/2158; Animals; Cell Culture Techniques - methods; Cell Line; Chimera; Cloning; Embryonic growth stage; Embryonic Stem Cells - cytology; Embryos; Epigenetics; Female; Gene expression; Germ Layers - cytology; Humanities and Social Sciences; Humans; Induced Pluripotent Stem Cells - cytology; Male; Metabolism; Mice; Morphology; multidisciplinary; Pan troglodytes; Pluripotent Stem Cells - cytology; Pluripotent Stem Cells - metabolism; Regenerative Medicine; Science; Species Specificity; Stem cells
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/nature14413

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. A previously unknown type of stem cell that can engraft in specific regions of the mouse epiblast is described; these region-selective pluripotent stem cells display notable intra- and inter-specific chimaera competency and will help to further our understanding of mammalian development. An alternative stem cell state Embryonic stem cells and epiblast stem cells represent two commonly accepted pluripotent states, derived from distinct time points during mouse embryogenesis. By modulating signalling components in the culture medium used for derivation of pluripotent stem cells from mouse epiblasts, Izpisua Belmonte and colleagues have identified an additional stem cell state with characteristics distinct from these two classes. These cells can engraft in specific regions of the mouse epiblast and are thus named region-selective pluripotent stem cells (rsPSCs). Cells with similar properties were also obtained from cultures of mouse and primate pluripotent stem cell lines. The study of rsPSCs will allow further understanding of mammalian development.