Skip to main content

Parthenogenetic Activation-Induced Pluripotent Stem Cells and Potential Applications

  • Chapter
  • First Online:
Stem Cells and Cancer Stem Cells, Volume 8

Part of the book series: Stem Cells and Cancer Stem Cells ((STEM,volume 8))

  • 1248 Accesses

Abstract

Parthenogenesis is the process by which an egg can develop into an embryo without fertilization. Parthenogenesis can be induced by artificial activation of an egg in mammals. Parthenogenetic embryos typically fail to develop past mid-gestation, mostly due to insufficient placental development. Therefore they should not be considered as living embryos. However, parthenogenetic embryonic stem (pES) cells can be generated from parthenogenetic embryos. While aberrant genomic imprinting limits development of parthenogenetic embryos, genomic imprinting undergoes reprogramming during isolation and culture of pES cells enabling pES cells developmental pluripotency and extensive differentiation capacity, similar to ES cells. Indeed, pES cells also are designated as parthenogenetic activation-induced pluripotent stem cells (paiPS). pES cells proliferate indefinitely and show genomic stability with minimal tumorigenesis, so they hold great promise for stem cell therapy. Damaged tissues and degenerative diseases could be treated by pES cells derived from patients’ own eggs, or from immunocompatible, banked pES cells. Presumably their derivation from a non viable embryo source would raise fewer ethical concerns than ES cells derived from embryos. Also, spare eggs are readily available from fertility clinics or can be retrieved from patients anticipating need for pES cell therapy. Patients facing radiation or chemo-therapy could bank eggs to preserve their fertility and also produce pES cells for potential cell therapy. This review focuses on the critical step for generation of pES, oocyte activation, reviews the mechanisms of genomic imprinting underlying pluripotency, provides an overview of potential applications of pES for clinical therapeutics, as well as potential drawbacks of pES cells and strategies to overcome those challenges.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Backs J, Stein P, Backs T, Duncan FE, Grueter CE, McAnally J, Qi X, Schultz RM, Olson EN (2009) The gamma isoform of CaM kinase II controls mouse egg activation by regulating cell cycle resumption. Proc Natl Acad Sci USA 107:81–86

    Article  PubMed  Google Scholar 

  • Barton SC, Surani MA, Norris ML (1984) Role of paternal and maternal genomes in mouse development. Nature 311:374–376

    Article  CAS  PubMed  Google Scholar 

  • Cheek TR, McGuinness OM, Vincent C, Moreton RB, Berridge MJ, Johnson MH (1993) Fertilisation and thimerosal stimulate similar calcium spiking patterns in mouse oocytes but by separate mechanisms. Development 119:179–189

    CAS  PubMed  Google Scholar 

  • Chen Z, Liu Z, Huang J, Amano T, Li C, Cao S, Wu C, Liu B, Zhou L, Carter MG, Keefe DL, Yang X, Liu L (2009) Birth of parthenote mice directly from parthenogenetic embryonic stem cells. Stem Cells 27:2136–2145

    Article  CAS  PubMed  Google Scholar 

  • De Sousa PA, Gardner J, Sneddon S, Pells S, Tye BJ, Dand P, Collins DM, Stewart K, Shaw L, Przyborski S, Cooke M, McLaughlin KJ, Kimber SJ, Lieberman BA, Wilmut I, Brison DR (2009) Clinically failed eggs as a source of normal human embryo stem cells. Stem Cell Res 2:188–197

    Article  PubMed  Google Scholar 

  • Deng MQ, Shen SS (2000) A specific inhibitor of p34(cdc2)/cyclin B suppresses fertilization-induced calcium oscillations in mouse eggs. Biol Reprod 62:873–878

    Article  CAS  PubMed  Google Scholar 

  • Eckardt S, Leu NA, Yanchik A, Hatada S, Kyba M, McLaughlin KJ (2011) Gene therapy by allele selection in a mouse model of beta-thalassemia. J Clin Invest 121:623–627

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fissore RA, Pinto-Correia C, Robl JM (1995) Inositol trisphosphate-induced calcium release in the generation of calcium oscillations in bovine eggs. Biol Reprod 53:766–774

    Article  CAS  PubMed  Google Scholar 

  • Fulka H, Hirose M, Inoue K, Ogonuki N, Wakisaka N, Matoba S, Ogura A, Mosko T, Kott T, Fulka J Jr (2011) Production of mouse embryonic stem cell lines from maturing oocytes by direct conversion of meiosis into mitosis. Stem Cells 29:517–527

    Article  CAS  PubMed  Google Scholar 

  • Hagemann LJ, Hillery-Weinhold FL, Leibfried Rutledge ML, First NL (1995) Activation of murine oocytes with Ca2+ ionophore and cycloheximide. J Exp Zool 271:57–61

    Article  CAS  PubMed  Google Scholar 

  • Hikichi T, Wakayama S, Mizutani E, Takashima Y, Kishigami S, Van Thuan N, Ohta H, Thuy Bui H, Nishikawa S, Wakayama T (2007) Differentiation potential of parthenogenetic embryonic stem cells is improved by nuclear transfer. Stem Cells 25:46–53

    Article  CAS  PubMed  Google Scholar 

  • Horii T, Kimura M, Morita S, Nagao Y, Hatada I (2008) Loss of genomic imprinting in mouse parthenogenetic embryonic stem cells. Stem Cells 26:79–88

    Article  CAS  PubMed  Google Scholar 

  • Hu Z, Wang L, Xie Z, Zhang X, Feng D, Wang F, Zuo B, Liu Z, Chen Z, Yang F, Liu L (2011) Quantitative proteomics analysis of parthenogenetically induced pluripotent stem cells. Protein Cell 2:631–646

    Article  CAS  PubMed  Google Scholar 

  • Huang J, Okuka M, Wang F, Zuo B, Liang P, Kalmbach K, Liu L, Keefe DL (2010) Generation of pluripotent stem cells from eggs of aging mice. Aging Cell 9:113–125

    Article  CAS  PubMed  Google Scholar 

  • Jedrusik A, Ajduk A, Pomorski P, Maleszewski M (2007) Mouse oocytes fertilised by ICSI during in vitro maturation retain the ability to be activated after refertilisation in metaphase II and can generate Ca2+ oscillations. BMC Dev Biol 7:72

    Article  PubMed Central  PubMed  Google Scholar 

  • Kim K, Lerou P, Yabuuchi A, Lengerke C, Ng K, West J, Kirby A, Daly MJ, Daley GQ (2007a) Histocompatible embryonic stem cells by parthenogenesis. Science 315:482–486

    Article  CAS  PubMed  Google Scholar 

  • Kim K, Ng K, Rugg-Gunn PJ, Shieh JH, Kirak O, Jaenisch R, Wakayama T, Moore MA, Pedersen RA, Daley GQ (2007b) Recombination signatures distinguish embryonic stem cells derived by parthenogenesis and somatic cell nuclear transfer. Cell Stem Cell 1:346–352

    Article  CAS  PubMed  Google Scholar 

  • Kono T (2006) Genomic imprinting is a barrier to parthenogenesis in mammals. Cytogenet Genome Res 113:31–35

    Article  CAS  PubMed  Google Scholar 

  • Kono T, Obata Y, Wu Q, Niwa K, Ono Y, Yamamoto Y, Park ES, Seo JS, Ogawa H (2004) Birth of parthenogenetic mice that can develop to adulthood. Nature 428:860–864

    Article  CAS  PubMed  Google Scholar 

  • Li C, Chen Z, Liu Z, Huang J, Zhang W, Zhou L, Keefe DL, Liu L (2009) Correlation of expression and methylation of imprinted genes with pluripotency of parthenogenetic embryonic stem cells. Hum Mol Genet 18:2177–2187

    Article  CAS  PubMed  Google Scholar 

  • Liu L, Ju JC, Yang X (1998) Parthenogenetic development and protein patterns of newly matured bovine oocytes after chemical activation. Mol Reprod Dev 49:298–307

    Article  CAS  PubMed  Google Scholar 

  • Liu L, Deng M, Tian X, Yang X (2002) Activation of mammalian oocytes: principles and practice. In: Tulsiani DRP (ed) Introduction to mammalian reproduction. Kluwer Academic Publishers, MA: Boston

    Google Scholar 

  • Liu N, Enkemann SA, Liang P, Hersmus R, Zanazzi C, Huang J, Wu C, Chen Z, Looijenga LH, Keefe DL, Liu L (2010) Genome-wide gene expression profiling reveals aberrant MAPK and Wnt signaling pathways associated with early parthenogenesis. J Mol Cell Biol 2:333–344

    Article  CAS  PubMed  Google Scholar 

  • Liu Z, Hu Z, Pan X, Li M, Togun TA, Tuck D, Pelizzola M, Huang J, Ye X, Yin Y, Liu M, Li C, Chen Z, Wang F, Zhou L, Chen L, Keefe DL, Liu L (2011) Germline competency of parthenogenetic embryonic stem cells from immature oocytes of adult mouse ovary. Hum Mol Genet 20:1339–1352

    Article  CAS  PubMed  Google Scholar 

  • Loren J, Lacham-Kaplan O (2006) The employment of strontium to activate mouse oocytes: effects on spermatid-injection outcome. Reproduction 131:259–267

    Article  CAS  PubMed  Google Scholar 

  • Lu Z, Zhu W, Yu Y, Jin D, Guan Y, Yao R, Zhang YA, Zhang Y, Zhou Q (2010) Derivation and long-term culture of human parthenogenetic embryonic stem cells using human foreskin feeders. J Assist Reprod Genet 27:285–291

    Article  PubMed  Google Scholar 

  • Mai Q, Yu Y, Li T, Wang L, Chen MJ, Huang SZ, Zhou C, Zhou Q (2007) Derivation of human embryonic stem cell lines from parthenogenetic blastocysts. Cell Res 17:1008–1019

    Article  CAS  PubMed  Google Scholar 

  • McGrath J, Solter D (1984) Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37:179–183

    Article  CAS  PubMed  Google Scholar 

  • Miyazaki S, Ito M (2006) Calcium signals for egg activation in mammals. J Pharmacol Sci 100:545–552

    Article  CAS  PubMed  Google Scholar 

  • Obata Y, Kaneko-Ishino T, Koide T, Takai Y, Ueda T, Domeki I, Shiroishi T, Ishino F, Kono T (1998) Disruption of primary imprinting during oocyte growth leads to the modified expression of imprinted genes during embryogenesis. Development 125:1553–1560

    CAS  PubMed  Google Scholar 

  • Presicce GA, Yang X (1994) Parthenogenetic development of bovine oocytes matured in vitro for 24 hr and activated by ethanol and cycloheximide. Mol Reprod Dev 38:380–385

    Article  CAS  PubMed  Google Scholar 

  • Revazova ES, Turovets NA, Kochetkova OD, Kindarova LB, Kuzmichev LN, Janus JD, Pryzhkova MV (2007) Patient-specific stem cell lines derived from human parthenogenetic blastocysts. Cloning Stem Cells 9:432–449

    Article  CAS  PubMed  Google Scholar 

  • Runft LL, Jaffe LA, Mehlmann LM (2002) Egg activation at fertilization: where it all begins. Dev Biol 245:237–254

    Article  CAS  PubMed  Google Scholar 

  • Sanchez-Pernaute R, Lee H, Patterson M, Reske-Nielsen C, Yoshizaki T, Sonntag KC, Studer L, Isacson O (2008) Parthenogenetic dopamine neurons from primate embryonic stem cells restore function in experimental Parkinson’s disease. Brain 131:2127–2139

    Article  PubMed  Google Scholar 

  • Tulsiani D (2003) Introduction to mammalian reproduction. Kluwer Academic Publishers, Boston

    Book  Google Scholar 

  • Vincent C, Cheek TR, Johnson MH (1992) Cell cycle progression of parthenogenetically activated mouse oocytes to interphase is dependent on the level of internal calcium. J Cell Sci 103(Pt 2):389–396

    CAS  PubMed  Google Scholar 

  • Wang WH, Abeydeera LR, Prather RS, Day BN (1998) Functional analysis of activation of porcine oocytes by spermatozoa, calcium ionophore, and electrical pulse. Mol Reprod Dev 51:346–353

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lin Liu .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Yin, Y., Liu, N., Keefe, D.L., Liu, L. (2012). Parthenogenetic Activation-Induced Pluripotent Stem Cells and Potential Applications. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 8. Stem Cells and Cancer Stem Cells, vol 8. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4798-2_22

Download citation

Publish with us

Policies and ethics