Animal Bioscience

  • 제38권3호
  • /
  • Pages.444-453
  • /
  • 2025
  • /
  • 2765-0189(pISSN)
  • /
  • 2765-0235(eISSN)
아세아태평양축산학회 (Asian Australasian Association of Animal Production Societies)
권호 표지
DOI QR코드

DOI QR Code

Mitochondrial morphology and energy metabolism in reprogrammed porcine expanded potential stem cells

  • Yun Ju Lee (Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University) ;
  • Jae Hoon Song (Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University) ;
  • Je Woo Lee (Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University) ;
  • Tae Kyung Hong (Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University) ;
  • Sang Jun Uhm (Department of Animal Science, Sangji University) ;
  • Kwonho Hong (Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University) ;
  • Jeong Tae Do (Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University)
  • 투고 : 2024.07.22
  • 심사 : 2024.08.26
  • 발행 : 2025.03.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Objective: Expanded potential stem cells (EPSCs) are stem cells that can differentiate into embryonic and extraembryonic lineages, including extraembryonic endoderm and trophoblast lineages. Therefore, EPSCs have great potential in advancing regenerative medicine, elucidating disease mechanisms, and exploring early embryonic development. However, the generation and characterization of EPSCs in pigs have not been thoroughly explored. In this study, we successfully generated porcine EPSCs (pEPSCs). Methods: We reprogrammed porcine fetal fibroblasts (PFFs) using an integration-free method with Sendai virus vectors. Results: The resulting pEPSCs expressed key pluripotency markers and demonstrated the ability to differentiate between embryonic and extraembryonic lineages. Notably, reprogramming into pEPSCs was associated with a transformation of mitochondrial morphology from the elongated form observed in PFFs to a globular shape, reflecting potential alterations in energy metabolism. We observed significant remodeling of mitochondrial morphology and a subsequent shift towards glycolytic energy dependence during the reprogramming of PFFs into pEPSCs. Conclusion: Our findings provide valuable insights into the characteristics of EPSCs in pigs and highlight their potential applications in regenerative medicine, disease modeling, and emerging fields such as cell-based meat production.

키워드

과제정보

This paper was supported by Konkuk University in 2024.

참고문헌

  1. Evans MJ, Kaufman MH. Establishment in culture of pluri­potential cells from mouse embryos. Nature 1981;292:154­6.https://doi.org/10.1038/292154a0
  2. Thomson JA, Itskovitz-­Eldor J, Shapiro SS, et al. Embryonicstem cell lines derived from human blastocysts. Science 1998;282:1145­7. https://doi.org/10.1126/science.282.5391.1145
  3. Nichols J, Smith A. Naive and primed pluripotent states. Cell Stem Cell 2009;4:487­92. https://doi.org/10.1016/j.stem.2009.05.015
  4. Beddington RS, Robertson EJ. An assessment of the developmental potential of embryonic stem cells in the midgestation mouse embryo. Development 1989;105:733-7. https://doi.org/10.1242/dev.105.4.733
  5. Yang J, Ryan DJ, Wang W, et al. Establishment of mouse expanded potential stem cells. Nature 2017;550:393­7.https://doi.org/10.1038/nature24052
  6. Gao X, Nowak-­Imialek M, Chen X, et al. Establishment ofporcine and human expanded potential stem cells. Nat Cell Biol 2019;21:687­99. https://doi.org/10.1038/s41556­019­0333­2
  7. Xu J, Yu L, Guo J, et al. Generation of pig induced pluripotent stem cells using an extended pluripotent stem cell culture system. Stem Cell Res Ther 2019;10:193. https://doi.org/10.1186/s13287­019­1303­0
  8. Xiang J, Wang H, Zhang Y, et al. LCDM medium supports the derivation of bovine extended pluripotent stem cells with embryonic and extraembryonic potency in bovine–mouse chimeras from iPSCs and bovine fetal fibroblasts. FEBS J 2021;288:4394­411. https://doi.org/10.1111/febs.15744
  9. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006;126:663­76. https://doi.org/10.1016/j.cell.2006.07.024
  10. Okita K, Nakagawa M, Hyenjong H, Ichisaka T, Yamanaka S. Generation of mouse induced pluripotent stem cells without viral vectors. Science 2008;322:949­53. https://doi.org/10.1126/science.1164270
  11. Nakanishi M, Otsu M. Development of Sendai virus vectors and their potential applications in gene therapy and regen­erative medicine. Curr Gene Ther 2012;12:410­6. https://doi.org/10.2174/156652312802762518
  12. Zhou H, Wu S, Joo JY, et al. Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 2009;4:381­4. https://doi.org/10.1016/j.stem.2009.04.005
  13. Warren L, Manos PD, Ahfeldt T, et al. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 2010;7:618­30. https://doi.org/10.1016/j.stem.2010.08.012
  14. Anokye-Danso F, Trivedi CM, Juhr D, et al. Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell 2011;8:376-88. https://doi.org/10.1016/j.stem.2011.03.001
  15. Hou P, Li Y, Zhang X, et al. Pluripotent stem cells induced from mouse somatic cells by small-­molecule compounds. Science 2013;341:651­4. https://doi.org/10.1126/science.
  16. Seo BJ, Choi J, La H, et al. Role of mitochondrial fission­related genes in mitochondrial morphology and energymetabolism in mouse embryonic stem cells. Redox Biol 2020;36:101599. https://doi.org/10.1016/j.redox.2020.101599
  17. Zick M, Rabl R, Reichert AS. Cristae formation-linking ultrastructure and function of mitochondria. Biochim Biophys Acta Mol Cell Res 2009;1793:5-19. https://doi.org/10.1016/j.bbamcr.2008.06.013
  18. Rossignol R, Gilkerson R, Aggeler R, Yamagata K, Remington SJ, Capaldi RA. Energy substrate modulates mitochondrial structure and oxidative capacity in cancer cells. Cancer Res 2004;64:985-93. https://doi.org/10.1158/0008-5472.can-03-1101
  19. Choi HW, Kim JH, Chung MK, et al. Mitochondrial and metabolic remodeling during reprogramming and differentiation of the reprogrammed cells. Stem Cells Dev 2015;24:1366-73. https://doi.org/10.1089/scd.2014.0561
  20. Seo BJ, Yoon SH, Do JT. Mitochondrial dynamics in stem cells and differentiation. Int J Mol Sci 2018;19:3893. https://doi.org/10.3390/ijms19123893
  21. Yang Y, Liu B, Xu J, et al. Derivation of pluripotent stem cells with in Vivo embryonic and extraembryonic potency. Cell 2017;169:243-57. https://doi.org/10.1016/j.cell.2017.02.005
  22. Choi HW, Kim JS, Choi S, et al. Neural stem cells differentiated from iPS cells spontaneously regain pluripotency. Stem Cells 2014:32:2596-604. https://doi.org/10.1002/stem.1757
  23. Yu Z, Zhou S, Liu M, et al. Porcine pluripotent stem cells established from LCDM medium with characteristics differ from human and mouse extended pluripotent stem cells. Stem Cells 2022;40:751-62. https://doi.org/10.1093/stmcls/sxac034
  24. Zhou W, Choi M, Margineantu D, et al. HIF1α induced switch from bivalent to exclusively glycolytic metabolism during ESC-to-EpiSC/hESC transition. EMBO J 2012;31:2103-16. https://doi.org/10.1038/emboj.2012.71
  25. Song JH, Choi J, Hong YJ, et al. Developmental potency and metabolic traits of extended pluripotency are faithfully transferred to somatic cells via cell fusion-induced repro-gramming. Cells 2022;11:3266. https://doi.org/10.3390/cells11203266
  26. Pfaff O, Hildebrandt C, Waelbroeck M, et al. The (S)-(+)-enantiomer of dimethindene: a novel M2-selective muscarinic receptor antagonist. Eur T Pharmacol 1995;286:229-40. https://doi.org/10.1016/0014-2999(9.2)00454-7
  27. Ockenga W, Kuhne S, Bocksberger S, Banning A, Tikkanen R. Non-neuronal functions of the m2 muscarinic acetylcholine receptor. Genes 2013;4:171-97. https://doi.org/10.3390/genes4020171
  28. Chang Q, Chen S, Yang T. The GPCR antagonistic drug CM-20 stimulates mitochondrial activity in human RPE cells. Open Biochem J 2022;16:e1874091X2206270. https://doi,org/10.2174/1874091X-v16-e2206270