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

doi:10.1038/s41587-019-0373-y

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

Research output: Contribution to journal › Letter › peer-review

74 Scopus citations

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 kidney^1,2. 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 lineages^3–7. 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 language	English
Pages (from-to)	297-302
Number of pages	6
Journal	Nature Biotechnology
Volume	38
Issue number	3
DOIs	https://doi.org/10.1038/s41587-019-0373-y
State	Published - 1 Mar 2020
Externally published	Yes

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41587-019-0373-y

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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

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title = "Generation of human endothelium in pig embryos deficient in ETV2",

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.",

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

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doi = "10.1038/s41587-019-0373-y",

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AU - Das, Satyabrata

AU - Koyano-Nakagawa, Naoko

AU - Gafni, Ohad

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AU - Singh, Bhairab N.

AU - Rasmussen, Tara

AU - Pan, Xiaoyan

AU - Choi, Kyung Dal

AU - Mickelson, Daniel

AU - Gong, Wuming

AU - Pota, Pruthvi

AU - Weaver, Cyprian V.

AU - Kren, Stefan

AU - Hanna, Jacob H.

AU - Yannopoulos, Demetris

AU - Garry, Mary G.

AU - Garry, Daniel J.

PY - 2020/3/1

Y1 - 2020/3/1

N2 - 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.

AB - 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.

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Generation of human endothelium in pig embryos deficient in ETV2

Abstract

ASJC Scopus subject areas

UN SDGs

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