Generation of human endothelium in pig embryos deficient in ETV2

Satyabrata Das, Naoko Koyano-Nakagawa, Ohad Gafni, Geunho Maeng, Bhairab N Singh, Tara Rasmussen, Xiaoyan Pan, Kyung-Dal Choi, Daniel Mickelson, Wuming Gong, Pruthvi Pota, Cyprian V Weaver, Stefan Kren, Jacob H Hanna, Demetris Yannopoulos, Mary G Garry, Daniel J Garry

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Abstract

The scarcity of donor organs may be addressed in the future by using pigs to grow humanized organs with lower potential for immunological rejection after transplantation in humans. Previous studies have demonstrated that interspecies complementation of rodent blastocysts lacking a developmental regulatory gene can generate xenogeneic pancreas and kidney1,2. However, such organs contain host endothelium, a source of immune rejection. We used gene editing and somatic cell nuclear transfer to engineer porcine embryos deficient in ETV2, a master regulator of hematoendothelial lineages3-7. ETV2-null pig embryos lacked hematoendothelial lineages and were embryonic lethal. Blastocyst complementation with wild-type porcine blastomeres generated viable chimeric embryos whose hematoendothelial cells were entirely donor-derived. ETV2-null blastocysts were injected with human induced pluripotent stem cells (hiPSCs) or hiPSCs overexpressing the antiapoptotic factor BCL2, transferred to synchronized gilts and analyzed between embryonic day 17 and embryonic day 18. In these embryos, all endothelial cells were of human origin.

Original languageEnglish (US)
Pages (from-to)297-302
Number of pages6
JournalNature biotechnology
Volume38
Issue number3
DOIs
StatePublished - Feb 24 2020

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PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

Cite this

Das, S., Koyano-Nakagawa, N., Gafni, O., Maeng, G., Singh, B. N., Rasmussen, T., Pan, X., Choi, K-D., Mickelson, D., Gong, W., Pota, P., Weaver, C. V., Kren, S., Hanna, J. H., Yannopoulos, D., Garry, M. G., & Garry, D. J. (2020). Generation of human endothelium in pig embryos deficient in ETV2. Nature biotechnology, 38(3), 297-302. https://doi.org/10.1038/s41587-019-0373-y