Interspecies Chimerism with Mammalian Pluripotent Stem Cells

Jun Wu, Aida Platero-Luengo, Masahiro Sakurai, Atsushi Sugawara, Maria Antonia Gil, Takayoshi Yamauchi, Keiichiro Suzuki, Yanina Soledad Bogliotti, Cristina Cuello, Mariana Morales Valencia, Daiji Okumura, Jingping Luo, Marcela Vilariño, Inmaculada Parrilla, Delia Alba Soto, Cristina A. Martinez, Tomoaki Hishida, Sonia Sánchez-Bautista, M. Llanos Martinez-Martinez, Huili WangAlicia Nohalez, Emi Aizawa, Paloma Martinez-Redondo, Alejandro Ocampo, Pradeep Reddy, Jordi Roca, Elizabeth A. Maga, Concepcion Rodriguez Esteban, W. Travis Berggren, Estrella Nuñez Delicado, Jeronimo Lajara, Isabel Guillen, Pedro Guillen, Josep M. Campistol, Emilio A. Martinez, Pablo Juan Ross, Juan Carlos Izpisua Belmonte

Research output: Contribution to journalArticle

172 Scopus citations

Abstract

Interspecies blastocyst complementation enables organ-specific enrichment of xenogenic pluripotent stem cell (PSC) derivatives. Here, we establish a versatile blastocyst complementation platform based on CRISPR-Cas9-mediated zygote genome editing and show enrichment of rat PSC-derivatives in several tissues of gene-edited organogenesis-disabled mice. Besides gaining insights into species evolution, embryogenesis, and human disease, interspecies blastocyst complementation might allow human organ generation in animals whose organ size, anatomy, and physiology are closer to humans. To date, however, whether human PSCs (hPSCs) can contribute to chimera formation in non-rodent species remains unknown. We systematically evaluate the chimeric competency of several types of hPSCs using a more diversified clade of mammals, the ungulates. We find that naïve hPSCs robustly engraft in both pig and cattle pre-implantation blastocysts but show limited contribution to post-implantation pig embryos. Instead, an intermediate hPSC type exhibits higher degree of chimerism and is able to generate differentiated progenies in post-implantation pig embryos.

Original languageEnglish (US)
Pages (from-to)473-486.e15
JournalCell
Volume168
Issue number3
DOIs
StatePublished - Jan 26 2017
Externally publishedYes

Keywords

  • CRISPR-Cas9
  • human naïve pluripotent stem cells
  • human-cattle chimeric embryo
  • human-pig chimeric embryo
  • interspecies blastocyst complementation
  • interspecies chimera
  • organ and tissue generation
  • pluripotent stem cells
  • zygote genome editing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Wu, J., Platero-Luengo, A., Sakurai, M., Sugawara, A., Gil, M. A., Yamauchi, T., Suzuki, K., Bogliotti, Y. S., Cuello, C., Morales Valencia, M., Okumura, D., Luo, J., Vilariño, M., Parrilla, I., Soto, D. A., Martinez, C. A., Hishida, T., Sánchez-Bautista, S., Martinez-Martinez, M. L., ... Izpisua Belmonte, J. C. (2017). Interspecies Chimerism with Mammalian Pluripotent Stem Cells. Cell, 168(3), 473-486.e15. https://doi.org/10.1016/j.cell.2016.12.036