TY - JOUR
T1 - Interspecies Chimerism with Mammalian Pluripotent Stem Cells
AU - Wu, Jun
AU - Platero-Luengo, Aida
AU - Sakurai, Masahiro
AU - Sugawara, Atsushi
AU - Gil, Maria Antonia
AU - Yamauchi, Takayoshi
AU - Suzuki, Keiichiro
AU - Bogliotti, Yanina Soledad
AU - Cuello, Cristina
AU - Morales Valencia, Mariana
AU - Okumura, Daiji
AU - Luo, Jingping
AU - Vilariño, Marcela
AU - Parrilla, Inmaculada
AU - Soto, Delia Alba
AU - Martinez, Cristina A.
AU - Hishida, Tomoaki
AU - Sánchez-Bautista, Sonia
AU - Martinez-Martinez, M. Llanos
AU - Wang, Huili
AU - Nohalez, Alicia
AU - Aizawa, Emi
AU - Martinez-Redondo, Paloma
AU - Ocampo, Alejandro
AU - Reddy, Pradeep
AU - Roca, Jordi
AU - Maga, Elizabeth A.
AU - Esteban, Concepcion Rodriguez
AU - Berggren, W. Travis
AU - Nuñez Delicado, Estrella
AU - Lajara, Jeronimo
AU - Guillen, Isabel
AU - Guillen, Pedro
AU - Campistol, Josep M.
AU - Martinez, Emilio A.
AU - Ross, Pablo Juan
AU - Izpisua Belmonte, Juan Carlos
N1 - Funding Information:
J.C.I.B. dedicates this paper to Dr. Rafael Matesanz, Director of the Spain's National Organ Transplant Organization. Rafael's work has helped save thousands of patients in need of an organ. He constitutes a relentless inspiration for those of us trying to understand and alleviate human disease. The authors are grateful to Xiomara Lucas, Maria Dolores Ortega, Moises Gonzalvez, Jose Antonio Godinez, and Jesus Gomis for their assistance throughout this work. We thank the staff of the Agropor S.A. and Porcisan S.A. piggeries (Murcia, Spain) for the help and excellent management of animals. We thank Joan Rowe, Bret McNabb, Aaron Prinz, and Kent Parker and their crews for excellent assistance with embryo transfers and pig care at UC Davis. We thank Mako Yamamoto for help with mouse embryo dissection. We would like to thank Uri Manor of the Salk Waitt Advanced Biophotonics Core for technical advice on imaging analysis. We would like to thank the Salk Stem Cell Core for providing cell culture reagents. We would like to thank May Schwarz and Peter Schwarz for administrative help. We thank David O'Keefe for critical reading and editing of the manuscript. This experimental study was supported by The Fundación Séneca (GERM 19892/GERM/15), Murcia, Spain. The MINECO is acknowledged for their grant-based support (BES-2013-064087 and BES-2013-064069) (to C.A.M and A.N.). P.J.R was supported by a UC Davis Academic Senate New Research grant. Work in the laboratory of J.C.I.B. was supported by the UCAM, Fundacion Dr. Pedro Guillen, G. Harold and Leila Y. Mathers Charitable Foundation, and The Moxie Foundation.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/1/26
Y1 - 2017/1/26
N2 - 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.
AB - 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.
KW - CRISPR-Cas9
KW - human naïve pluripotent stem cells
KW - human-cattle chimeric embryo
KW - human-pig chimeric embryo
KW - interspecies blastocyst complementation
KW - interspecies chimera
KW - organ and tissue generation
KW - pluripotent stem cells
KW - zygote genome editing
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U2 - 10.1016/j.cell.2016.12.036
DO - 10.1016/j.cell.2016.12.036
M3 - Article
C2 - 28129541
AN - SCOPUS:85010695864
SN - 0092-8674
VL - 168
SP - 473-486.e15
JO - Cell
JF - Cell
IS - 3
ER -