Format

Send to

Choose Destination
Cell. 2017 Jan 26;168(3):473-486.e15. doi: 10.1016/j.cell.2016.12.036.

Interspecies Chimerism with Mammalian Pluripotent Stem Cells.

Author information

1
Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.
2
Department of Animal Medicine and Surgery, University of Murcia Campus de Espinardo, 30100 Murcia, Spain.
3
Department of Animal Science, University of California Davis, One Shields Avenue, Davis, CA 95616, USA.
4
Universidad Católica San Antonio de Murcia (UCAM) Campus de los Jerónimos, N° 135 Guadalupe 30107 Murcia, Spain.
5
Clinica Centro Fundación Pedro Guillén, Clínica CEMTRO, Avenida Ventisquero de la Condesa 42, 28035 Madrid, Spain.
6
Universidad Católica San Antonio de Murcia (UCAM) Campus de los Jerónimos, N° 135 Guadalupe 30107 Murcia, Spain; Clinica Centro Fundación Pedro Guillén, Clínica CEMTRO, Avenida Ventisquero de la Condesa 42, 28035 Madrid, Spain.
7
Hospital Clínico de Barcelona-IDIBAPS, Universitat de Barcelona, 08007 Barcelona, Spain.
8
Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: belmonte@salk.edu.

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.

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

PMID:
28129541
PMCID:
PMC5679265
DOI:
10.1016/j.cell.2016.12.036
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center