Generation of rat blood vasculature and hematopoietic cells in rat-mouse chimeras by blastocyst complementation

Xiaomin Wang; Hui Shi; Juanjuan Zhou; Qingjian Zou; Quanjun Zhang; Shixue Gou; Pengfei Chen; Lisha Mou; Nana Fan; Yangyang Suo; Zhen Ouyang; Chengdan Lai; Quanmei Yan; Liangxue Lai

doi:10.1016/j.jgg.2020.05.002

Volume 47 Issue 5

May 2020

Turn off MathJax

Article Contents

Article Navigation > Journal of Genetics and Genomics > 2020 > 47(5): 249-261

PDF( 5470 KB)

Generation of rat blood vasculature and hematopoietic cells in rat-mouse chimeras by blastocyst complementation

doi: 10.1016/j.jgg.2020.05.002

Xiaomin Wang^{a, b, 1},
Hui Shi^{a, b, 1},
Juanjuan Zhou^{a, i, 1},
Qingjian Zou^f,
Quanjun Zhang^{a, c, d, e},
Shixue Gou^{a, b},
Pengfei Chen^{g, h},
Lisha Mou^g,
Nana Fan^{a, c, d, e},
Yangyang Suo^{a, j},
Zhen Ouyang^{a, c, d, e},
Chengdan Lai^{a, c, d, e},
Quanmei Yan^{a, c, d, e},
Liangxue Lai^{a, c, d, e, f, j}

a
CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China
b
University of Chinese Academy of Sciences, Beijing, 100049, China
c
Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou, 510005, China
d
Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China
e
Research Unit of Generation of Large Animal Disease Models, Chinese Academy of Medical Sciences (2019RU015), Guangzhou, 510530, China
f
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, 529020, China
g
Shenzhen Xenotransplantation Medical Engineering Research and Development Center, Institute of Translational Medicine, Shenzhen University Health Science Center, Shenzhen University School of Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518035, China
h
Department of Central Laboratory, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, China
i
School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China
j
Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, 511436, China

More Information

Corresponding author: E-mail address: yan_quanmei@gibh.ac.cn (Quanmei Yan); E-mail address: lai_liangxue@gibh.ac.cn (Liangxue Lai)
Publish Date: 2020-05-25

Abstract

Abstract

Interspecies chimera through blastocyst complementation could be an alternative approach to create human organs in animals by using human pluripotent stem cells. A mismatch of the major histocompatibility complex of vascular endothelial cells between the human and host animal will cause graft rejection in the transplanted organs. Therefore, to achieve a transplantable organ in animals without rejection, creation of vascular endothelial cells derived from humans within the organ is necessary. In this study, to explore whether donor xeno-pluripotent stem cells can compensate for blood vasculature in host animals, we generated rat-mouse chimeras by injection of rat embryonic stem cells (rESCs) into mouse blastocysts with deficiency of Flk-1 protein, which is associated with endothelial and hematopoietic cell development. We found that rESCs could differentiate into vascular endothelial and hematopoietic cells in the rat-mouse chimeras. The whole yolk sac (YS) of Flk-1 rat-mouse chimera was full of rat blood vasculature. Rat genes related to vascular endothelial cells, arteries, and veins, blood vessels formation process, as well as hematopoietic cells, were highly expressed in the YS. Our results suggested that rat vascular endothelial cells could undergo proliferation, migration, and self-assembly to form blood vasculature and that hematopoietic cells could differentiate into B cells, T cells, and myeloid cells in rat-mouse chimeras, which was able to rescue early embryonic lethality caused byFlk-1 deficiency in mouse.
- Blastocyst complementation,
- Interspecies chimera,
- Intraspecies chimera,
- Vascular endothelial cell,
- Hematopoietic cell

These authors contributed equally to this work.

FullText(HTML)

References(40)

References

[1]	Bandopadhyay, R., Orte, C., Lawrenson, J.G., Reid, A.R., De, S.S., and Allt, G. 2001. Contractile proteins in pericytes at the blood-brain and blood-retinal barriers. J. Neurocytol. 30, 35-44.
[2]	Carmeliet, P. 2000a. Mechanisms of angiogenesis and arteriogenesis. Nat. Med. 6, 389-395.
[3]	Carmeliet, P. 2000b. Developmental biology. One cell, two fates. Nature 408, 43-45.
[4]	Cooney, A.J., Tsukiyama, T., Kato-Itoh, M., Nakauchi, H., and Ohinata, Y. 2014. A comprehensive system for generation and evaluation of induced pluripotent stem cells using piggyBac transposition. PloS One 9, e92973.
[5]	Costa, G., Kouskoff, V., and Lacaud, G. 2012. Origin of blood cells and HSC production in the embryo. Trends Immunol. 33, 215-223.
[6]	Crisan, M., Corselli, M., Chen, W.C., and Peault, B. 2012. Perivascular cells for regenerative medicine. J. Cell Mol. Med. 16, 2851-2860.
[7]	Crisan, M., Yap, S., Casteilla, L., Chen, C.W., Corselli, M., Park, T.S., Andriolo, G., Sun, B., Zheng, B., Zhang, L., Norotte, C., Teng, P.N., Traas, J., Schugar, R., Deasy, B.M., Badylak, S., Buhring, H.J., Giacobino, J.P., Lazzari, L., Huard, J., and Peault, B. 2008. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3, 301-313.
[8]	Cross, M.J., Dixelius, J., Matsumoto, T., and Claesson-Welsh, L. 2003. VEGF-receptor signal transduction. Trends Biochem. Sci. 28, 488-494.
[9]	Du, C., Narayanan, K., Leong, M.F., Ibrahim, M.S., Chua, Y.P., Khoo, V.M., and Wan, A.C. 2016. Functional kidney bioengineering with pluripotent stem-cell-derived renal progenitor cells and decellularized kidney scaffolds. Adv Healthc Mater 5, 2080-2091.
[10]	Gomes, M.E., Rodrigues, M.T., Domingues, R.M.A., and Reis, R.L. 2017. Tissue engineering and regenerative medicine: new trends and directions-a year in review. Tissue Eng. B Rev. 23, 211-224.
[11]	Goto, T., Hara, H., Sanbo, M., Masaki, H., Sato, H., Yamaguchi, T., Hochi, S., Kobayashi, T., Nakauchi, H., and Hirabayashi, M. 2019. Generation of pluripotent stem cell-derived mouse kidneys in Sall1-targeted anephric rats. Nat. Commun. 10, 451.
[12]	Hall, A.P. 2006. Review of the pericyte during angiogenesis and its role in cancer and diabetic retinopathy. Toxicol. Pathol. 34, 763-775.
[13]	Hamanaka, S., Umino, A., Sato, H., Hayama, T., Yanagida, A., Mizuno, N., Kobayashi, T., Kasai, M., Suchy, F.P., Yamazaki, S., Masaki, H., Yamaguchi, T., and Nakauchi, H. 2018. Generation of vascular endothelial cells and hematopoietic cells by blastocyst complementation. Stem Cell Rep 11, 988-997.
[14]	Huang, K., Zhu, Y., Ma, Y., Zhao, B., Fan, N., Li, Y., Song, H., Chu, S., Ouyang, Z., Zhang, Q., Xing, Q., Lai, C., Li, N., Zhang, T., Gu, J., Kang, B., Shan, Y., Lai, K., Huang, W., Mai, Y., Wang, Q., Li, J., Lin, A., Zhang, Y., Zhong, X., Liao, B., Lai, L., Chen, J., Pei, D., and Pan, G. 2018. BMI1 enables interspecies chimerism with human pluripotent stem cells. Nat. Commun. 9, 4649.
[15]	Isotani, A., Hatayama, H., Kaseda, K., Ikawa, M., and Okabe, M. 2011. Formation of a thymus from rat ES cells in xenogeneic nude mouse<-->rat ES chimeras. Gene Cell. 16, 397-405.
[16]	Kitahara, H., Yagi, H., Tajima, K., Okamoto, K., Yoshitake, A., Aeba, R., Kudo, M., Kashima, I., Kawaguchi, S., Hirano, A., Kasai, M., Akamatsu, Y., Oka, H., Kitagawa, Y., and Shimizu, H. 2016. Heterotopic transplantation of a decellularized and recellularized whole porcine heart. Interact. Cardiovasc. Thorac. Surg. 22, 571-579.
[17]	Kobayashi, T., Yamaguchi, T., Hamanaka, S., Kato-Itoh, M., Yamazaki, Y., Ibata, M., Sato, H., Lee, Y.S., Usui, J., Knisely, A.S., Hirabayashi, M., and Nakauchi, H. 2010. Generation of rat pancreas in mouse by interspecific blastocyst injection of pluripotent stem cells. Cell 142, 787-799.
[18]	Kubis, N., and Levy, B.I. 2003. Vasculogenesis and angiogenesis: molecular and cellular controls. Part 1: growth factors. Intervent Neuroradiol. 9, 227-237.
[19]	Lacaud, G., and Kouskoff, V. 2017. Hemangioblast, hemogenic endothelium, and primitive versus definitive hematopoiesis. Exp. Hematol. 49, 19-24.
[20]	Lux, C.T., Yoshimoto, M., McGrath, K., Conway, S.J., Palis, J., and Yoder, M.C. 2008. All primitive and definitive hematopoietic progenitor cells emerging before E10 in the mouse embryo are products of the yolk sac. Blood 111, 3435-3438.
[21]	Mascetti, V.L., and Pedersen, R.A. 2016. Human-mouse chimerism validates human stem cell pluripotency. Cell Stem Cell 18, 67-72.
[22]	Mazzini, L., Gelati, M., Profico, D.C., Sgaravizzi, G., Projetti Pensi, M., Muzi, G., Ricciolini, C., Rota Nodari, L., Carletti, S., Giorgi, C., Spera, C., Domenico, F., Bersano, E., Petruzzelli, F., Cisari, C., Maglione, A., Sarnelli, M.F., Stecco, A., Querin, G., Masiero, S., Cantello, R., Ferrari, D., Zalfa, C., Binda, E., Visioli, A., Trombetta, D., Novelli, A., Torres, B., Bernardini, L., Carriero, A., Prandi, P., Servo, S., Cerino, A., Cima, V., Gaiani, A., Nasuelli, N., Massara, M., Glass, J., Soraru, G., Boulis, N.M., and Vescovi, A.L. 2015. Human neural stem cell transplantation in ALS: initial results from a phase I trial. J. Transl. Med. 13, 17.
[23]	Ozerdem, U., and Stallcup, W.B. 2003. Early contribution of pericytes to angiogenic sprouting and tube formation. Angiogenesis 6, 241-249.
[24]	Palis, J., Robertson, S., Kennedy, M., Wall, C., and Keller, G. 1999. Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. Development 126, 5073-5084.
[25]	Patel, J.J., Srivastava, S., and Siow, R.C. 2016. Isolation, culture, and characterization of vascular smooth muscle cells. Methods Mol. Biol. 1430, 91-105.
[26]	Pettinato, G., Lehoux, S., Ramanathan, R., Salem, M.M., He, L.X., Muse, O., Flaumenhaft, R., Thompson, M.T., Rouse, E.A., Cummings, R.D., Wen, X., and Fisher, R.A. 2019. Generation of fully functional hepatocyte-like organoids from human induced pluripotent stem cells mixed with Endothelial Cells. Sci. Rep. 9, 8920.
[27]	Picelli, S., Faridani, O.R., Bjorklund, A.K., Winberg, G., Sagasser, S., and Sandberg, R. 2014. Full-length RNA-seq from single cells using Smart-seq2. Nat. Protoc. 9, 171-181.
[28]	Raza, A., Franklin, M.J., and Dudek, A.Z. 2010. Pericytes and vessel maturation during tumor angiogenesis and metastasis. Am. J. Hematol. 85, 593-598.
[29]	Sakurai, Y., Ohgimoto, K., Kataoka, Y., Yoshida, N., and Shibuya, M. 2004. Essential role of Flk-1 (VEGF receptor 2) tyrosine residue 1173 in vasculogenesis in mice. Proc. Natl. Acad. Sci. U. S. A. 102, 1076-1081.
[30]	Sakurai, Y., Ohgimoto, K., Kataoka, Y., Yoshida, N., and Shibuya, M. 2005. Essential role of Flk-1 (VEGF receptor 2) tyrosine residue 1173 in vasculogenesis in mice. Proc. Natl. Acad. Sci. U. S. A. 102, 1076-1081.
[31]	Salaris, F., and Rosa, A. 2019. Construction of 3D in vitro models by bioprinting human pluripotent stem cells: challenges and opportunities. Brain Res. 1723, 146393.
[32]	Shalaby, F., Ho, J., Stanford, W.L., Fischer, K.D., Schuh, A.C., Schwartz, L., Bernstein, A., and Rossant, J. 1997a. A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis. Cell 89, 981-990.
[33]	Shalaby, F., Rossant, J., Yamaguchi, T.P., Gertsenstein, M., Wu, X.F., Breitman, M.L., and Schuh, A.C. 1995. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 376, 62-66.
[34]	Shalaby F., Ho J., Stanford W.L., Fischer K.D., Schuh A.C., Schwartz L., Bernstein A., and J., R. 1997b. A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis. Cell 89, 981-990.
[35]	van Dijk, C.G., Nieuweboer, F.E., Pei, J.Y., Xu, Y.J., Burgisser, P., van Mulligen, E., el Azzouzi, H., Duncker, D.J., Verhaar, M.C., and Cheng, C. 2015. The complex mural cell: pericyte function in health and disease. Int. J. Cardiol. 190, 75-89.
[36]	Wang, X., Li, T., Cui, T., Yu, D., Liu, C., Jiang, L., Feng, G., Wang, L., Fu, R., Zhang, X., Hao, J., Wang, Y., Wang, L., Zhou, Q., Li, W., and Hu, B. 2018. Human embryonic stem cells contribute to embryonic and extraembryonic lineages in mouse embryos upon inhibition of apoptosis. Cell Res. 28, 126-129.
[37]	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., Vilarino, M., Parrilla, I., Soto, D.A., Martinez, C.A., Hishida, T., Sanchez-Bautista, S., Martinez-Martinez, M.L., Wang, H., Nohalez, A., Aizawa, E., Martinez-Redondo, P., Ocampo, A., Reddy, P., Roca, J., Maga, E.A., Esteban, C.R., Berggren, W.T., Nunez Delicado, E., Lajara, J., Guillen, I., Guillen, P., Campistol, J.M., Martinez, E.A., Ross, P.J., and Izpisua Belmonte, J.C. 2017. Interspecies chimerism with mammalian pluripotent stem cells. Cell 168, 473-486.
[38]	Yamaguchi, T., Sato, H., Kato-Itoh, M., Goto, T., Hara, H., Sanbo, M., Mizuno, N., Kobayashi, T., Yanagida, A., Umino, A., Ota, Y., Hamanaka, S., Masaki, H., Rashid, S.T., Hirabayashi, M., and Nakauchi, H. 2017. Interspecies organogenesis generates autologous functional islets. Nature 542, 191-196.
[39]	Yang, Y., Liu, B., Xu, J., Wang, J., Wu, J., Shi, C., Xu, Y., Dong, J., Wang, C., Lai, W., Zhu, J., Xiong, L., Zhu, D., Li, X., Yang, W., Yamauchi, T., Sugawara, A., Li, Z., Sun, F., Li, X., Li, C., He, A., Du, Y., Wang, T., Zhao, C., Li, H., Chi, X., Zhang, H., Liu, Y., Li, C., Duo, S., Yin, M., Shen, H., Belmonte, J.C.I., and Deng, H. 2017. Derivation of pluripotent stem cells with in vivo embryonic and extraembryonic potency. Cell 169, 243-257.
[40]	Zhou, Q., Li, L., and Li, J. 2015. Stem cells with decellularized liver scaffolds in liver regeneration and their potential clinical applications. Liver Int. 35, 687-694.