Reprogramming of the pig primordial germ cells into pluripotent stem cells: a brief review

Abstract

Primordial germ cells (PGCs) are regarded as unipotent cells that can produce only either spermatogonia or oocytes. However, PGCs can be converted into the pluripotent state by first dedifferentiation to embryonic germ cells and then by reprogramming to induce them to become pluripotent stem cells (iPSCs). These two stages can be completely implemented with mouse cells. However, authentic porcine iPSCs have not been established. Here, we discuss recent advances in the stem cell field for obtaining iPSCs from PGCs. This knowledge will provide some clues which will contribute to the regulation of reprogramming to pluripotency in farm species.

Keywords

pig / pluripotent stem cells / primordial germ cells / reprogramming

References

[1] Bertocchini F, Chuva de Sousa Lopes S M. Germline development in amniotes: a paradigm shift in primordial germ cell specification. BioEssays, 2016, 38(8): 791–800

[2] Kimura T, Kaga Y, Sekita Y, Fujikawa K, Nakatani T, Odamoto M, Funaki S, Ikawa M, Abe K, Nakano T. Pluripotent stem cells derived from mouse primordial germ cells by small molecule compounds. Stem Cells, 2015, 33(1): 45–55

[3] Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 2007, 131(5): 861–872

[4] Park I H, Zhao R, West J A, Yabuuchi A, Huo H, Ince T A, Lerou P H, Lensch M W, Daley G Q. Reprogramming of human somatic cells to pluripotency with defined factors. Nature, 2008, 451(7175): 141–146

[5] Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K. Induced pluripotent stem cells generated without viral integration. Science, 2008, 322(5903): 945–949

[6] Li Y, Zhang Q, Yin X, Yang W, Du Y, Hou P, Ge J, Liu C, Zhang W, Zhang X, Wu Y, Li H, Liu K, Wu C, Song Z, Zhao Y, Shi Y, Deng H. Generation of iPSCs from mouse fibroblasts with a single gene, Oct4, and small molecules. Cell Research, 2011, 21(1): 196–204

[7] Lin T, Ambasudhan R, Yuan X, Li W, Hilcove S, Abujarour R, Lin X, Hahm H S, Hao E, Hayek A, Ding S. A chemical platform for improved induction of human iPSCs. Nature Methods, 2009, 6(11): 805–808

[8] Matsui Y, Zsebo K, Hogan B L. Derivation of pluripotential embryonic stem cells from murine primordial germ cells in culture. Cell, 1992, 70(5): 841–847

[9] Bazley F A, Liu C F, Yuan X, Hao H, All A H, De Los Angeles A, Zambidis E T, Gearhart J D, Kerr C L. Direct reprogramming of human primordial germ cells into induced pluripotent stem cells: efficient generation of genetically engineered germ cells. Stem Cells and Development, 2015, 24(22): 2634–2648

[10] Kobayashi T, Zhang H, Tang W W C, Irie N, Withey S, Klisch D, Sybirna A, Dietmann S, Contreras D A, Webb R, Allegrucci C, Alberio R, Surani M A. Principles of early human development and germ cell program from conserved model systems. Nature, 2017, 546(7658): 416–420

[11] McLaren A. Primordial germ cells in the mouse. Developmental Biology, 2003, 262(1): 1–15

[12] Ohinata Y, Payer B, O’Carroll D, Ancelin K, Ono Y, Sano M, Barton S C, Obukhanych T, Nussenzweig M, Tarakhovsky A, Saitou M, Surani M A. Blimp1 is a critical determinant of the germ cell lineage in mice. Nature, 2005, 436(7048): 207–213

[13] Nagamatsu G, Saito S, Takubo K, Suda T. Integrative analysis of the acquisition of pluripotency in PGCs reveals the mutually exclusive roles of Blimp-1 and AKT signaling. Stem Cell Reports, 2015, 5(1): 111–124

[14] Yamaji M, Seki Y, Kurimoto K, Yabuta Y, Yuasa M, Shigeta M, Yamanaka K, Ohinata Y, Saitou M. Critical function of Prdm14 for the establishment of the germ cell lineage in mice. Nature Genetics, 2008, 40(8): 1016–1022

[15] Klisch K, Contreras D A, Sun X, Brehm R, Bergmann M, Alberio R. The Sda/GM2-glycan is a carbohydrate marker of porcine primordial germ cells and of a subpopulation of spermatogonia in cattle, pigs, horses and llama. Reproduction, 2011, 142(5): 667–674

[16] Zhang Y, Ma J, Li H, Lv J, Wei R, Cong Y, Liu Z. bFGF signaling-mediated reprogramming of porcine primordial germ cells. Cell and Tissue Research, 2016, 364(2): 429–441

[17] Goel S, Sugimoto M, Minami N, Yamada M, Kume S, Imai H. Identification, isolation, and in vitro culture of porcine gonocytes. Biology of Reproduction, 2007, 77(1): 127–137

[18] Hyldig S M W, Ostrup O, Vejlsted M, Thomsen P D. Changes of DNA methylation level and spatial arrangement of primordial germ cells in embryonic day 15 to embryonic day 28 pig embryos. Biology of Reproduction, 2011, 84(6): 1087–1093

[19] Petkov S G, Reh W A, Anderson G B. Methylation changes in porcine primordial germ cells. Molecular Reproduction & Development, 2009, 76(1): 22

[20] Hyldig S M, Croxall N, Contreras D A, Thomsen P D and Alberio R. Epigenetic reprogramming in the porcine germ line. BMC Developmental Biology, 2011, 11(1): 1–11

[21] Ruggiu M, Speed R, Taggart M, McKay S J, Kilanowski F, Saunders P, Dorin J, Cooke H J. The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis. Nature, 1997, 389(6646): 73–77

[22] Tanaka S S, Toyooka Y, Akasu R, Katoh-Fukui Y, Nakahara Y, Suzuki R, Yokoyama M, Noce T. The mouse homolog of Drosophila Vasa is required for the development of male germ cells. Genes & Development, 2000, 14(7): 841–853

[23] Masui S, Nakatake Y, Toyooka Y, Shimosato D, Yagi R, Takahashi K, Okochi H, Okuda A, Matoba R, Sharov A A, Ko M S, Niwa H. Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nature Cell Biology, 2007, 9(6): 625–635

[24] Silva J, Nichols J, Theunissen T W, Guo G, van Oosten A L, Barrandon O, Wray J, Yamanaka S, Chambers I, Smith A. Nanog is the gateway to the pluripotent ground state. Cell, 2009, 138(4): 722–737

[25] Resnick J L, Bixler L S, Cheng L, Donovan P J. Long-term proliferation of mouse primordial germ cells in culture. Nature, 1992, 359(6395): 550–551

[26] Lopeziglesias P, Alcaina Y, Tapia N, Sabour D, Arauzobravo M J, Sainz de la Maza D, Berra E, O’Mara A N, Nistal M, Ortega S, Donovan P J, Schöler H R, De Miguel M P, Sainz d l M D, Berra E, Nunezomara A, Nistal M and Ortega S. Hypoxia induces pluripotency in primordial germ cells by HIF1a stabilization and Oct4 deregulation. Antioxidants & Redox Signalling, 2015, 22(3): 205–223

[27] Chen L R, Shiue Y L, Bertolini L, Medrano J F, BonDurant R H, Anderson G B. Establishment of pluripotent cell lines from porcine preimplantation embryos. Theriogenology, 1999, 52(2): 195–212

[28] Vassiliev I, Vassilieva S, Beebe L F S, Harrison S J, McIlfatrick S M, Nottle M B. In vitro and in vivo characterization of putative porcine embryonic stem cells. Cellular Reprogramming, 2010, 12(2): 223–230

[29] Shim H, Gutiérrez-Adán A, Chen L R, BonDurant R H, Behboodi E, Anderson G B. Isolation of pluripotent stem cells from cultured porcine primordial germ cells. Theriogenology, 1997, 57(5): 1089–1095

[30] Piedrahita J A, Moore K, Oetama B, Lee C K, Scales N, Ramsoondar J, Bazer F W, Ott T. Generation of transgenic porcine chimeras using primordial germ cell-derived colonies. Biology of Reproduction, 1998, 58(5): 1321–1329

[31] Dong X, Tsung H, Mu Y, Liu L, Chen H, Zhang L, Wang H, Feng S. Generation of chimeric piglets by injection of embryonic germ cells from inbred Wuzhishan miniature pigs into blastocysts. Xenotransplantation, 2014, 21(2): 140–148

[32] West F D, Terlouw S L, Kwon D J, Mumaw J L, Dhara S K, Hasneen K, Dobrinsky J R, Stice S L. Porcine induced pluripotent stem cells produce chimeric offspring. Stem Cells and Development, 2010, 19(8): 1211–1220

[33] Du X, Feng T, Yu D, Wu Y, Zou H, Ma S, Feng C, Huang Y, Ouyang H, Hu X, Pan D, Li N, Wu S. Barriers for deriving transgenefree pig iPS cells with episomal vectors. Stem Cells, 2015, 33(11): 3228–3238

[34] Chakritbudsabong W, Sariya L, Pamonsupornvichit S, Pronarkngver R, Chaiwattanarungruengpaisan S, Ferreira J N, Setthawong P, Phakdeedindan P, Techakumphu M, Tharasanit T, Rungarunlert S. Generation of a pig induced pluripotent stem cell (piPSC) line from embryonic fibroblasts by incorporating LIN28 to the four transcriptional factor-mediated reprogramming: VSMUi001-D. Stem Cell Research, 2017, 24: 21–24

[35] Montserrat N, Bahima E G, Batlle L, Häfner S, Rodrigues A M, González F, Izpisúa Belmonte J C. Generation of pig iPS cells: a model for cell therapy. Journal of Cardiovascular Translational Research, 2011, 4(2): 121–130

[36] Ezashi T, Telugu B P V L, Alexenko A P, Sachdev S, Sinha S, Roberts R M. Derivation of induced pluripotent stem cells from pig somatic cells. Proceedings of the National Academy of Sciences of the United States of America, 2009, 106(27): 10993–10998

[37] Wu Y, Li O, He C, Li Y, Li M, Liu X L, Wang Y, He Y. Generation and characterization of induced pluripotent stem cells from guinea pig fetal fibroblasts. Molecular Medicine Reports, 2017, 15(6): 3690–3698

[38] Hall V. Porcine embryonic stem cells: a possible source for cell replacement therapy. Stem Cell Reviews, 2008, 4(4): 275–282

[39] Onishi A, Iwamoto M, Akita T, Mikawa S, Takeda K, Awata T, Hanada H, Perry A C. Pig cloning by microinjection of fetal fibroblast nuclei. Science, 2000, 289(5482): 1188–1190

[40] Polejaeva I A, Chen S H, Vaught T D, Page R L, Mullins J, Ball S, Dai Y, Boone J, Walker S, Ayares D L, Colman A, Campbell K H. Cloned pigs produced by nuclear transfer from adult somatic cells. Nature, 2000, 407(6800): 86–90

[41] Maherali N, Sridharan R, Xie W, Utikal J, Eminli S, Arnold K, Stadtfeld M, Yachechko R, Tchieu J, Jaenisch R, Plath K, Hochedlinger K. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell, 2007, 1(1): 55–70

[42] Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein B E, Jaenisch R. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature, 2007, 448(7151): 318–324

[43] Pashai N, Hao H, All A, Gupta S, Chaerkady R, De Los Angeles A, Gearhart J D, Kerr C L. Genome-wide profiling of pluripotent cells reveals a unique molecular signature of human embryonic germ cells. PLoS One, 2012, 7(6): e39088

[44] Saitou M, Kagiwada S, Kurimoto K. Epigenetic reprogramming in mouse pre-implantation development and primordial germ cells. Development, 2012, 139(1): 15–31

[45] Mise N, Fuchikami T, Sugimoto M, Kobayakawa S, Ike F, Ogawa T, Tada T, Kanaya S, Noce T, Abe K. Differences and similarities in the developmental status of embryo-derived stem cells and primordial germ cells revealed by global expression profiling. Genes to Cells, 2008, 13(8): 863–877

[46] Niwa H, Miyazaki J, Smith A G. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nature Genetics, 2000, 24(4): 372–376

[47] Yamaguchi S, Kimura H, Tada M, Nakatsuji N, Tada T. Nanog expression in mouse germ cell development. Gene Expression Patterns Gep, 2005, 5(5): 639–646

Acknowledgements

This work was supported by the National Basic Research Program of China (2016YFA0100203) and the National Natural Science Foundation of China (31572399, 31272518).

Compliance with ethics guidelines

Qijing Lei, Qin Pan, Shuai Yu, Na Li, Shulin Chen, Kuldip Sidhu, and Jinlian Hua declare that they have no conflicts of interest or financial conflicts to disclose.

This article is a review and does not contain any studies with human or animal subjects performed by any of the authors.

RIGHTS & PERMISSIONS

The Author(s) 2018. Published by Higher Education Press. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0)