DOI QR코드

DOI QR Code

Pluripotent stem cells from the perspective of developmental potential and their characteristics

  • In-Won Lee (Department of Animal Bioscience, College of Agriculture & Life Sciences, Gyeongsang National University) ;
  • Sang-Ki Baek (Gyeongsangnamdo Livestock Experiment Station) ;
  • Yeon-Ji Lee (Department of Animal Bioscience, College of Agriculture & Life Sciences, Gyeongsang National University) ;
  • Tae-Suk Kim (Department of Animal Bioscience, College of Agriculture & Life Sciences, Gyeongsang National University) ;
  • Bo-Gyeong Seo (Division of Life Science, College of Natural Sciences, Gyeongsang National University) ;
  • Cheol Hwangbo (Division of Life Science, College of Natural Sciences, Gyeongsang National University) ;
  • Joon-Hee Lee (Department of Animal Bioscience, College of Agriculture & Life Sciences, Gyeongsang National University)
  • Received : 2024.12.09
  • Accepted : 2024.12.24
  • Published : 2024.12.31

Abstract

Pluripotent stem cells (PSCs) are undifferentiated cells with the potential to develop into all cell types in the body. They have the potential to replenish cells in tissues and organs, and have unique properties that make them a powerful tool for regenerative therapy. Embryonic stem cells (ESCs) derived from the inner cell mass of the blastocyst of pre-implantation embryo and epiblast stem cells (EpiSCs) derived from the epiblast layer of post-implantation embryo are the well-known PSCs. These stem cells can differentiate into any of three germ layers of germ cells (endoderm, mesoderm and ectoderm). Additionally, induced pluripotent stem cells (iPSCs) refer to adult somatic cells reprogrammed to return to the pluripotent state by introducing specific factors. This is a breakthrough in stem cell research because ethical concerns such as fertilized embryo destruction can be avoided. PSCs have tremendous potential in treating degenerative cells by generating the cells needed to replace damaged cells, which can also allow to generate specific cell types to study the mechanisms of the disease and create disease models that screen for potential drugs. However, if the proliferative capacity of PSCs is not controlled, there is a risk that tumors will form, as this can lead to uncontrolled growth in their proliferative capacity. In addition, when PSCs are used for therapeutic purposes, there is a risk that the body's immune system rejects the transplanted cells when the transplanted cells do not originate from the patient's own tissue. Taken together, PSC is the foundation of stem cell research and regenerative medicine, providing disease treatment and animal development understanding. We would like to explain the classification of PSCs based on their developmental potential, the types of PSCs (ESCs, EpiSCs and iPSCs), their pluripotent status (naïve vs. primed) and alkaline phosphatase (AP) in PSCs and PSCs in domestic animals.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea funded by the Korean Government (2020R1l1A3072689) Republic of Korea. In-Won Lee, Yeon-Ji Lee and Bo-Gyeong Seo were supported by the scholarship from the BK21Plus Program, Ministry of Education, Republic of Korea.

References

  1. Alberio R, Croxall N, Allegrucci C. 2010. Pig epiblast stem cells depend on activin/nodal signaling for pluripotency and self-renewal. Stem Cells Dev. 19:1627-1636. https://doi.org/10.1089/scd.2010.0012
  2. Aboul-Soud MAM, Alzahrani AJ, Mahmoud A. 2021. Induced pluripotent stem cells (iPSCs)-roles in regenerative therapies, disease modelling and drug screening. Cells 10:2319.
  3. Baek SK, Jeon SB, Seo BG, Hwangbo C, Shin KC, Choi JW, An CS, Jeong MA, Kim TS, Lee JH. 2021. The presence or absence of alkaline phosphatase activity to discriminate pluripotency characteristics in porcine epiblast stem cell-like cells. Cell Reprogram. 23:221-238. https://doi.org/10.1089/cell.2021.0014
  4. Baek SK, Lee IW, Lee YJ, Seo BG, Choi JW, Kim TS, Hwangbo C, Lee JH. 2023. Comparative pluripotent characteristics of porcine induced pluripotent stem cells generated using different viral transduction systems. J. Anim. Reprod. Biotechnol. 38:275-290. https://doi.org/10.12750/JARB.38.4.275
  5. Bayerl J, Ayyash M, Shani T, Manor YS, Gafni O, Massarwa R, Kalma Y, Aguilera-Castrejon A, Zerbib M, Amir H, Sheban D, Geula S, Mor N, Weinberger L, Naveh Tassa S, Krupalnik V, Oldak B, Livnat N, Tarazi S, Tawil S, Wildschutz E, Ashouokhi S, Lasman L, Rotter V, Hanna S, Ben-Yosef D, Novershtern N, Viukov S, Hanna JH. 2021. Principles of signaling pathway modulation for enhancing human naive pluripotency induction. Cell Stem Cell 28:1549-1565.e12. https://doi.org/10.1016/j.stem.2021.04.001
  6. Blanpain C, Horsley V, Fuchs E. 2007. Epithelial stem cells: turning over new leaves. Cell 128:445-458. https://doi.org/10.1016/j.cell.2007.01.014
  7. Brons IG, Smithers LE, Trotter MW, Rugg-Gunn P, Sun B, Chuva de Sousa Lopes SM, Howlett SK, Clarkson A, Ahrlund Richter L, Pedersen RA, Vallier L. 2007. Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448:191-195. https://doi.org/10.1038/nature05950
  8. Buecker C, Chen HH, Polo JM, Daheron L, Bu L, Barakat TS, Okwieka P, Porter A, Gribnau J, Hochedlinger K, Geijsen N. 2010. A murine ESC-like state facilitates transgenesis and homologous recombination in human pluripotent stem cells. Cell Stem Cell 6:535-546. https://doi.org/10.1016/j.stem.2010.05.003
  9. Chen LR, Shiue YL, Bertolini L, Medrano JF, BonDurant RH, Anderson GB. 1999. Establishment of pluripotent cell lines from porcine preimplantation embryos. Theriogenology 52:195-212. https://doi.org/10.1016/S0093-691X(99)00122-3
  10. Choi IY, Lim H, Lee G. 2014. Efficient generation human induced pluripotent stem cells from human somatic cells with Sendai-virus. J. Vis. Exp. 86:51406. https://doi.org/10.3791/51406-v
  11. Dahéron L, Opitz SL, Zaehres H, Lensch MW, Andrews PW, Itskovitz-Eldor J, Daley GQ. 2004. LIF/STAT3 signaling fails to maintain self-renewal of human embryonic stem cells. Stem Cells 22:770-778. https://doi.org/10.1634/stemcells.22-5-770
  12. Eistetter HR. 1988. A mouse pluripotent embryonal stem cell line stage-specifically regulates expression of homeo-box containing DNA sequences during differentiation in vitro. Eur. J. Cell Biol 45:315-321.
  13. Esteban MA, Xu J, Yang J, Peng M, Qin D, Li W, Jiang Z, Chen J, Deng K, Zhong M, Cai J, Lai L, Pei D. 2009. Generation of induced pluripotent stem cell lines from Tibetan miniature pig. J. Biol. Chem. 284:17634-17640. https://doi.org/10.1074/jbc.M109.008938
  14. Evans MJ and Kaufman MH. 1981. Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154-156. https://doi.org/10.1038/292154a0
  15. Evans MJ, Notarianni S, Laurie S, Moor RM. 1990. Derivation and preliminary characterization of pluripotent cell lines from porcine and bovine blastocysts. Theriogenology 33:125-128. https://doi.org/10.1016/0093-691X(90)90603-Q
  16. Ezashi T, Telugu BP, Alexenko AP, Sachdev S, Sinha S, Roberts RM. 2009. Derivation of induced pluripotent stem cells from pig somatic cells. Proc. Natl. Acad. Sci. U. S. A. 106:10993-10998. https://doi.org/10.1073/pnas.0905284106
  17. Fusaki N, Ban H, Nishiyama A, Saeki K, Hasegawa M. 2009. Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 85:348-362. https://doi.org/10.2183/pjab.85.348
  18. Gandolfi F, Pennarossa G, Maffei S, Brevini T. 2012. Why is it so difficult to derive pluripotent stem cells in domestic ungulates? Reprod. Domest. Anim. 47 Suppl 5:11-7. https://doi.org/10.1111/j.1439-0531.2012.02106.x
  19. Ginis I, Luo Y, Miura T, Thies S, Brandenberger R, Gerecht-Nir S, Amit M, Hoke A, Carpenter MK, Itskovitz-Eldor J, Rao MS. 2004. Differences between human and mouse embryonic stem cells. Dev. Biol. 269:360-380. https://doi.org/10.1016/j.ydbio.2003.12.034
  20. Gong G, Roach ML, Jiang L, Yang X, Tian XC. 2010. Culture conditions and enzymatic passaging of bovine ESC-like cells. Cell Reprogram. 12:151-160. https://doi.org/10.1089/cell.2009.0049
  21. Han DW, Tapia N, Joo JY, Greber B, Araúzo-Bravo MJ, Bernemann C, Ko K, Wu G, Stehling M, Do JT, Schöler HR. 2010. Epiblast stem cell subpopulations represent mouse embryos of distinct pregastrulation stages. Cell 143:617-627. https://doi.org/10.1016/j.cell.2010.10.015
  22. Hanna J, Cheng AW, Saha K, Kim J, Lengner CJ, Soldner F, Cassady JP, Muffat J, Carey BW, Jaenisch R. 2010a. Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs. Proc. Natl. Acad. Sci. U. S. A. 107:9222-9227. https://doi.org/10.1073/pnas.1004584107
  23. Hanna JH, Saha K, Jaenisch R. 2010b. Pluripotency and cellular reprogramming: facts, hypotheses, unresolved issues. Cell 143:508-525. https://doi.org/10.1016/j.cell.2010.10.008
  24. Heard E. 2004. Recent advances in X-chromosome inactivation. Curr. Opin. Cell. Biol. 16:247-255. https://doi.org/10.1016/j.ceb.2004.03.005
  25. Hima BA and Srilatha B. 2011. Potency of various types of stem cells and their transplantation. J. Stem Cell Res. Ther. 1:3.
  26. Hochereau-de Reviers MT and Perreau C. 1993. In vitro culture of embryonic disc cells from porcine blastocysts. Reprod. Nutr. Dev. 33:475-483. https://doi.org/10.1051/rnd:19930508
  27. Jaenisch R and Young R. 2008. Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell 132:567-582. https://doi.org/10.1016/j.cell.2008.01.015
  28. Jeon SB, Seo BG, Baek SK, Lee HG, Shin JH, Lee IW, Kim HJ, Moon SY, Shin KC, Choi JW, Kim TS, Lee JH, Hwangbo C. 2021. Endothelial cells differentiated from porcine epiblast stem cells. Cell Reprogram. 23:89-98. https://doi.org/10.1089/cell.2020.0088
  29. Karagiannis P, Takahashi K, Saito M, Yoshida Y, Okita K, Watanabe A, Inoue H, Yamashita JK, Todani M, Nakagawa M, Osawa M, Yashiro Y, Yamanaka S, Osafune K. 2019. Induced pluripotent stem cells and their use in human models of disease and development. Physiol. Rev. 99:79-114. https://doi.org/10.1152/physrev.00039.2017
  30. Keefer CL, Pant D, Blomberg L, Talbot NC. 2007. Challenges and prospects for the establishment of embryonic stem cell lines of domesticated ungulates. Anim. Reprod. Sci. 98:147-168. https://doi.org/10.1016/j.anireprosci.2006.10.009
  31. Kim D, Kim CH, Moon JI, Chung YG, Chang MY, Han BS, Ko S, Yang E, Cha KY, Lanza R, Kim KS. 2009. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4:472-476. https://doi.org/10.1016/j.stem.2009.05.005
  32. Kobayashi E, Enosawa S, Nagashima H. 2017. Experimental hepatocyte transplantation in pigs. Methods Mol. Biol. 1506:149-160. https://doi.org/10.1007/978-1-4939-6506-9_10
  33. Kues WA and Niemann H. 2011. Advances in farm animal transgenesis. Prev. Vet. Med. 102:146-156. https://doi.org/10.1016/j.prevetmed.2011.04.009
  34. Lee JB, Kim JM, Kim SJ, Park JH, Hong SH, Roh SI, Kim MK, Yoon HS. 2005. Comparative characteristics of three human embryonic stem cell lines. Mol. Cells. 19:31-38. https://doi.org/10.1016/S1016-8478(23)24499-4
  35. Leitch HG, Okamura D, Durcova-Hills G, Stewart CL, Gardner RL, Matsui Y, Papaioannou VE. 2014. On the fate of primordial germ cells injected into early mouse embryos. Dev. Biol. 385:155-159. https://doi.org/10.1016/j.ydbio.2013.11.014
  36. Levitt MD, Hapak SM, Levitt DG. 2022. Alkaline phosphatase pathophysiology with emphasis on the seldom-discussed role of defective elimination in unexplained elevations of serum alp - a case report and literature review. Clin. Exp. Gastroenterol. 15:41-49. https://doi.org/10.2147/CEG.S345531
  37. Li P, Tong C, Mehrian-Shai R, Jia L, Wu N, Yan Y, Maxson RE, Schulze EN, Song H, Hsieh CL, Pera MF, Ying QL. 2008. Germline competent embryonic stem cells derived from rat blastocysts. Cell 135:1299-1310. https://doi.org/10.1016/j.cell.2008.12.006
  38. Li W, Wei W, Zhu S, Zhu J, Shi Y, Lin T, Hao E, Hayek A, Deng H, Ding S. 2009. Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors. Cell Stem Cell 4:16-19. https://doi.org/10.1016/j.stem.2008.11.014
  39. Liu H, Yang H, Zhu D, Sui X, Li J, Liang Z, Xu L, Chen Z, Yao A, Zhang L, Zhang X, Yi X, Liu M, Xu S, Zhang W, Lin H, Xie L, Lou J, Zhang Y, Xi J, Deng H. 2014. Systematically labeling developmental stage-specific genes for the study of pancreatic β-cell differentiation from human embryonic stem cells. Cell Res. 24:1181-1200. https://doi.org/10.1038/cr.2014.118
  40. Martin GR. 1981. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc. Natl. Acad. Sci. U. S. A. 78:7634-7638. https://doi.org/10.1073/pnas.78.12.7634
  41. Najm FJ, Chenoweth JG, Anderson PD, Nadeau JH, Redline RW, McKay RD, Tesar PJ. 2011. Isolation of epiblast stem cells from preimplantation mouse embryos. Cell Stem Cell 8:318-325. https://doi.org/10.1016/j.stem.2011.01.016
  42. Nichols J and Smith A. 2009. Naive and primed pluripotent states. Cell Stem Cell 4:487-492. https://doi.org/10.1016/j.stem.2009.05.015
  43. Niemann H and Kues WA. 2007. Transgenic farm animals: an update. Reprod. Fertil. Dev. 19:762-770. https://doi.org/10.1071/RD07040
  44. Nowak-Imialek M, Kues W, Carnwath JW, Niemann H. 2011. Pluripotent stem cells and reprogrammed cells in farm animals. Microsc. Microanal. 17:474-497. https://doi.org/10.1017/S1431927611000080
  45. O'Connor MD, Kardel MD, Iosfina I, Youssef D, Lu M, Li MM, Vercauteren S, Nagy A, Eaves CJ. 2008. Alkaline phosphatase-positive colony formation is a sensitive, specific, and quantitative indicator of undifferentiated human embryonic stem cells. Stem Cells 26:1109-1116. https://doi.org/10.1634/stemcells.2007-0801
  46. Odorico JS, Kaufman DS, Thomson JA. 2001. Multilineage differentiation from human embryonic stem cell lines. Stem Cells 19:193-204. https://doi.org/10.1634/stemcells.19-3-193
  47. Okita K and Yamanaka S. 2010. Induction of pluripotency by defined factors. Exp. Cell Res 316:2565-2570. https://doi.org/10.1016/j.yexcr.2010.04.023
  48. Ozawa M, Sakatani M, Hankowski KE, Terada N, Dobbs KB, Hansen PJ. 2012. Importance of culture conditions during the morula-to-blastocyst period on capacity of inner cell mass cells of bovine blastocysts for establishment of selfrenewing pluripotent cells. Theriogenology 78:1243-51.e1-2. https://doi.org/10.1016/j.theriogenology.2012.05.020
  49. Pant D and Keefer CL. 2009. Expression of pluripotency-related genes during bovine inner cell mass explant culture. Cloning Stem Cells 11:355-365. https://doi.org/10.1089/clo.2008.0078
  50. Pashaiasl M, Khodadadi K, Holland MK, Verma PJ. 2010. The efficient generation of cell lines from bovine parthenotes. Cell Reprogram. 12:571-579. https://doi.org/10.1089/cell.2009.0118
  51. Patel S, Bonora G, Sahakyan A, Kim R, Chronis C, Langerman J, Fitz-Gibbon S, Rubbi L, Skelton RJP, Ardehali R, Pellegrini M, Lowry WE, Clark AT, Plath K. 2017. Human embryonic stem cells do not change their x inactivation status during differentiation. Cell Rep. 18:54-67. https://doi.org/10.1016/j.celrep.2016.11.054
  52. Piedrahita JA, Anderson GB, Bondurant RH. 1990. On the isolation of embryonic stem cells: comparative behavior of murine, porcine and ovine embryos. Theriogenology 34:879-901. https://doi.org/10.1016/0093-691X(90)90559-C
  53. Reubinoff BE, Pera MF, Fong CY, Trounson A, Bongso A. 2000. Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat. Biotechnol. 18:399-404. https://doi.org/10.1038/74447
  54. Romito A and Cobellis G. 2016. Pluripotent stem cells: current understanding and future directions. Stem Cells Int. 2016:9451492. https://doi.org/10.1155/2016/9451492
  55. Rossant J. 2008. Stem cells and early lineage development. Cell 132:527-531. https://doi.org/10.1016/j.cell.2008.01.039
  56. Rostovskaya M, Stirparo GG, Smith A. 2019. Capacitation of human naïve pluripotent stem cells for multi-lineage differentiation. Development 146:dev172916. https://doi.org/10.1242/dev.172916
  57. Shamblott MJ, Axelman J, Wang S, Bugg EM, Littlefield JW, Donovan PJ, Blumenthal PD, Huggins GR, Gearhart JD. 1998. Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc. Natl. Acad. Sci. U. S. A. 95:13726-13731. https://doi.org/10.1073/pnas.95.23.13726
  58. Shin JH, Seo BG, Lee IW, Kim HJ, Seo EC, Lee KM, Jeon SB, Baek SK, Kim TS, Lee JH, Choi JW, Hwangbo C, Lee JH. 2022. Functional characterization of endothelial cells differentiated from porcine epiblast stem cells. Cells 11:1524. https://doi.org/10.3390/cells11091524
  59. Smith AG, Heath JK, Donaldson DD, Wong GG, Moreau J, Stahl M, Rogers D. 1988. Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature 336:688-690. https://doi.org/10.1038/336688a0
  60. Stadtfeld M and Hochedlinger K. 2010. Induced pluripotency: history, mechanisms, and applications. Genes Dev. 24:2239-2263. https://doi.org/10.1101/gad.1963910
  61. Štefková K, Procházková J, Pacherník J. 2015. Alkaline phosphatase in stem cells. Stem Cells Int. 2015:628368. https://doi.org/10.1155/2015/628368
  62. Strojek RM, Reed MA, Hoover JL, Wagner TE. 1990. A method for cultivating morphologically undifferentiated embryonic stem cells from porcine blastocysts. Theriogenology 33:901-913. https://doi.org/10.1016/0093-691X(90)90825-E
  63. Surrati A, Linforth R, Fisk ID, Sottile V, Kim DH. 2016. Nondestructive characterisation of mesenchymal stem cell differentiation using LC-MS-based metabolite footprinting. Analyst 141:3776-3787. https://doi.org/10.1039/C6AN00170J
  64. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861-872. https://doi.org/10.1016/j.cell.2007.11.019
  65. Takahashi K and Yamanaka S. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663-676. https://doi.org/10.1016/j.cell.2006.07.024
  66. Telugu BP, Ezashi T, Roberts RM. 2010. The promise of stem cell research in pigs and other ungulate species. Stem Cell Rev. Rep. 6:31-41. https://doi.org/10.1007/s12015-009-9101-1
  67. ten Berge D, Kurek D, Blauwkamp T, Koole W, Maas A, Eroglu E, Siu RK, Nusse R. 2011. Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells. Nat. Cell Biol. 13:1070-1075. https://doi.org/10.1038/ncb2314
  68. Tesar PJ, Chenoweth JG, Brook FA, Davies TJ, Evans EP, Mack DL, Gardner RL, McKay RD. 2007. New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature 448:196-199. https://doi.org/10.1038/nature05972
  69. Thomson AJ, Pierart H, Meek S, Bogerman A, Sutherland L, Murray H, Mountjoy E, Downing A, Talbot R, Sartori C, Whitelaw CB, Freeman TC, Archibald AL, Burdon T. 2012. Reprogramming pig fetal fibroblasts reveals a functional LIF signaling pathway. Cell Reprogram 14:112-122. https://doi.org/10.1089/cell.2011.0078
  70. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. 1998. Embryonic stem cell lines derived from human blastocysts. Science 282:1145-1147. https://doi.org/10.1126/science.282.5391.1145
  71. Thomson JA, Kalishman J, Golos TG, Durning M, Harris CP, Becker RA, Hearn JP. 1995. Isolation of a primate embryonic stem cell line. Proc. Natl. Acad. Sci. U. S. A. 92:7844-7848. https://doi.org/10.1073/pnas.92.17.7844
  72. Tian Z, Yu T, Liu J, Wang T, Higuchi A. 2023. Introduction to stem cells. Prog. Mol. Biol. Transl. Sci. 199:3-32. https://doi.org/10.1016/bs.pmbts.2023.02.012
  73. Trusler O, Huang Z, Goodwin J, Laslett AL. 2018. Cell surface markers for the identification and study of human naive pluripotent stem cells. Stem Cell Res. 26:36-43. https://doi.org/10.1016/j.scr.2017.11.017
  74. Vallier L and Pedersen RA. 2005. Human embryonic stem cells: an in vitro model to study mechanisms controlling pluripotency in early mammalian development. Stem Cell Rev. 1:119-130. https://doi.org/10.1385/SCR:1:2:119
  75. Vimalraj S. 2020. Alkaline phosphatase: structure, expression and its function in bone mineralization. Gene 754:144855.
  76. Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A, Daley GQ, Brack AS, Collins JJ, Cowan C, Schlaeger TM, Rossi DJ. 2010. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7:618-630. https://doi.org/10.1016/j.stem.2010.08.012
  77. Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH. 1997. Viable offspring derived from fetal and adult mammalian cells. Nature 385:810-813. https://doi.org/10.1038/385810a0
  78. Wu B, Tian S, Hu R, Gao H, Yan B, Wang H, Zheng Y, Zhang Y, Wang Y. 2022a. Unbalanced development and progressive repair in human early mosaic and chimeric embryos. Med. Hypotheses 168:110967. https://doi.org/10.1016/j.mehy.2022.110967
  79. Wu JX, Xia T, She LP, Lin S, Luo XM. 2022b. Stem cell therapies for human infertility: advantages and challenges. Cell Transplant. 31:9636897221083252. https://doi.org/10.1177/09636897221083252
  80. Wu Z, Chen J, Ren J, Bao L, Liao J, Cui C, Rao L, Li H, Gu Y, Dai H, Zhu H, Teng X, Cheng L, Xiao L. 2009. Generation of pig induced pluripotent stem cells with a drug-inducible system. J. Mol. Cell Biol. 1:46-54. https://doi.org/10.1093/jmcb/mjp003
  81. Yamanaka S. 2007. Strategies and new developments in the generation of patient-specific pluripotent stem cells. Cell Stem Cell 1:39-49. https://doi.org/10.1016/j.stem.2007.05.012
  82. Yamanaka S. 2020. Pluripotent stem cell-based cell therapy promise and challenges. Cell Stem Cell 27:523-531. https://doi.org/10.1016/j.stem.2020.09.014
  83. Ying QL, Nichols J, Chambers I, Smith A. 2003. BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell 115:281-292. https://doi.org/10.1016/S0092-8674(03)00847-X
  84. Yu L, Wei Y, Duan J, Schmitz DA, Sakurai M, Wang L, Wang K, Zhao S, Hon GC, Wu J. 2021. Blastocyst-like structures generated from human pluripotent stem cells. Nature 591:620-626. https://doi.org/10.1038/s41586-021-03356-y