Open Access Peer-reviewed

Main Phenotype Subphases in Reprogramming Somatic Cells as a Model of Cellular Differentiation Process

Victor Valdespino1,, Patricia M Valdespino2, Victor Valdespino Junio3

1Health Attention Department, Universidad Autónoma Metropolitana, México

2Institute of Ecology. Universidad Nacional Autónoma de México, México

3Medical Ambulatory Attention Unit. Instituto Mexicano del Seguro Social, México

American Journal of Biomedical Research. 2013, 1(3), 48-56. DOI: 10.12691/ajbr-1-3-2
Published online: August 25, 2017

Abstract

The cellular differentiation process involves complex genetic, epigenetic and signaling pathways systems. The analysis of a specific model of cellular differentiation may contribute to understand the global mechanisms. The cellular differentiation process based on the experimental reprogramming of somatic cells (terminally differentiated cells) to induced pluripotent stem cells (iPSCs) can be used a study model of cellular differentiation. The cellular differentiation process includes constitutive changes in DNA damage response, chromatin remodeling, nuclear receptors, cell cycle regulation, apoptosis induction, cell adhesion and motility changes, immune recognition, metabolism routes, intercellular communication and in response to environment signals. It also includes the acquisition of changes into specialized cell subphenotypes as changes of shape, overproduction of organelles, suborganelles, control position of the mitotic spindle, preferential-transit signaling pathways and production of biomolecules with specialized functions. Different temporo-spatial genetic/epigenetic gene expression patterns and translational and posttranslational processes have been shown in the reprogramming of somatic cells. We analyze the main phenotype changes from fibroblast to iPSC (in cell cycle and cell adhesion/motility) to come after reprogramming, and use these changes as a model of cellular differentiation process.

Keywords:

cellular differentiation model, reprogramming, induced pluripotent stem cells, phenotype subphase
[1]  Iglesias-Bartolome R, Gutkind JS.” Signaling circuitries controlling stem cell fate: to be or not to be”. Current Opin Cell Biol, 23(6):716-723, Dec. 2011.View Article  PubMed
 
[2]  Cohen DE, Melton D. “Turning Straw into gold: directing cell fate for regenerative medicine”. Nat Rev Gen,12 (4):243-252. Apr. 2011View Article  PubMed
 
[3]  Izpisua JCB. “Reprogramming development and aging: cell differentiation as a malleable process”. Curr Opin Cell Biol, 24:713-715. Dec. 2012.View Article  PubMed
 
[4]  Sabour D, Schoeler HR. “Reprogramming and the mammalian germline: the Weismann barrier revisited”. Curr Opin Cell Biol, 24:716-723. Dec. 2012.View Article  PubMed
 
[5]  Takahashi K, Yamanaka S. “Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors”. Cell,126 (4):663-676. Aug. 2006.View Article  PubMed
 
[6]  Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. “Induction of pluripotent stem cells from adult human fibroblast by defined factors”. Cell, 131:861-872. Nov. 2007.View Article  PubMed
 
[7]  Sanges D. Cosma MP.” Reprogramming cell fate to pluripotency: the decision-making signaling pathways”. Int J Dev Biol, 54 (11-12):1575-1587. 2010.View Article  PubMed
 
[8]  Plath K, Lowry WE. “Progress in undestanding reprogramming to the induced pluripotent state”. Nat Rev Gen, 12(4):253-26., Apr. 2011.View Article  PubMed
 
[9]  Nie B, Wang H, Laurent T, Ding S. “Cellular reprogramming: a small molecule perspective”. Curr Opin Cell Biol, 24:784-792. Dec. 2012.View Article  PubMed
 
[10]  Narsinh KH, Sun N, Sanchez-Freire V, Lee AS, Almeida P, Hu S, et al. “Single cell transcriptional profiling reveals heterogeneity of human induced pluripotent stem cells”. J Clin Invest,121(3):1217-1222. Mar. 2011.View Article  PubMed
 
[11]  Valdespino V, Valdespino PM, Valdespino VJr. “Genomic-epigenomic signaling pathways changes in celular differentitation process”. Am J Biomed Res, 1(2):35-42, 2013.View Article
 
[12]  Stadtfeld M, Maherali N, Breaullt DT, Hochedlinger K. “Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse”. Cell Stem Cell, 2(3):230-240. Mar. 2008.View Article  PubMed
 
[13]  Paap B, Plath K. “Reprogramming to pluripotency: stepwise resetting of the epigenetic landscape”. Cell Res, 21(3):486-501. Mar. 2011.View Article  PubMed
 
[14]  Taby R. Ossa JP. “Cancer epigenetics”. CA Cancer J Clin, 60(6):376-392.Nov-Dec. 2010.View Article  PubMed
 
[15]  Polo JM, Liu S, Figueroa ME, Kulalert W, Eminli S, Tan KY, et al. “Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells”. Nat Biotechol, 28(8):848-855. Aug. 2010.View Article  PubMed
 
[16]  Rando TA, Chang HY. “Aging, rejuvenation, and epigenetic reprogramming: resetting the aging clock”. Cell, 148 (1-2):46-57. Jan. 2012.View Article  PubMed
 
[17]  Mahmoudi S, Brunet A. “Aging and reprogramming: a tow-way street”. Curr Opin Cell Biol, 24:744-756. Dec. 2012.View Article  PubMed
 
[18]  Freije JMP, Lopez-Otin C. “Reprogramming aging and progeria”. Curr Opin Cell Biol, 24:757-764. Dec. 2012.View Article  PubMed
 
[19]  Liu GH, Ding Z, Izpisua JCB. “IPSC technology to study human aging and aging-related disorders”. Curr Opin Cell Biol, 24:765-774. Dec. 2012.View Article  PubMed
 
[20]  Furusawa C, Kaneko K. “A dynamical-systems view of stem cell biology”. Science, 228(6104):215-217. Oct. 2012.View Article  PubMed
 
[21]  Xu RH, Peck RM, Li DS, Feng X, Ludwing T, Thomson JA. “Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cells”. Nat Methods, 2 (3):185-190. Mar. 2005.View Article  PubMed
 
[22]  Ng HH, Surani MA. “The transcriptional and signaling networks of pluripotency”. Nat Cell Biol, 13(5):490-496, May.2011.
 
[23]  Banito A, Rashid ST, Acosta JC, Li S, Pereira CF, Geti I, et al. “Senescence impairs successful reprogramming to pluripotent stem cells”. Genes Dev, 23(18):2134-2139. Sep. 2009.View Article  PubMed
 
[24]  Meshorer E, Misteli T. “Chromatin in pluripotent embryonic stem cells and differentiation”. Nat Rev Mol Cell Biol, 7(7):540-546. Jul. 2006.View Article  PubMed
 
[25]  Heng JC, Feng B, Han J, Jiang J, Kraus P, Ng JH, et al. “The nuclear receptor Nr5a2 can replace Oct4 the reprogramming of murine somatic cells to pluripotent cells”. Cell Stem Cell, 6(2):167-174. Feb. 2010.View Article  PubMed
 
[26]  Denholtz M, Plath K.” Pluripotency in 3D:genome organization in pluripotent”. Cell Stem Cell, 24(6):793-801. Dec. 2012.
 
[27]  Zhu S, Li W, Zhou H, Wei W, Ambasudhan R, Lin T, et al. “Reprogramming of human primary somatic cells by OCT4 and chemical compounds” Cell Stem Cell, 7(6):651-655. Dec. 2010.View Article  PubMed
 
[28]  Samavarchi-Tehrani P, Golipour A, David L, Sung HK, Beyer TA, Datti A, et al. “Functional genomics reveals a BMP-driven mesenchymal-to-epithelial transition in the initiation of somatic cell reprogramming” Cell Stem Cell, 7(1):64-77. Jul. 2010.View Article  PubMed
 
[29]  Li R, Liang J, Ni S, Zhou T, Qing X, Li H, He W, et al. “A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblast”. Cell Stem Cell, 7(1):51-63. Jul. 2010.View Article  PubMed
 
[30]  Castanon I, Gonazlez-Gaitan M. “Oriented cell division in vertebrate embryogenesis” Curr Opin Cell Biol, 23:697-704. Dec. 2011.View Article  PubMed
 
[31]  Hussein SM, Batada NN, Vuoristo S, Ching RW, Autio R, Narva E, et al. “Copy number variation and selection during reprogramming to pluripotency”. Nature, 471(7336): 58-62. Mar. 2011.View Article  PubMed
 
[32]  Lister R, Pelizzola M, Kida YS, Hawkins RD, Nery JR, Hon G, et al. “Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells”. Nature, 471(7336):68-73. Mar. 2011.View Article  PubMed
 
[33]  Robinton DA, Daley GQ. “The promise of induced pluripotent stem cells in research and therapy”. Nature, 481(7381):295-306. Jan. 2012.View Article  PubMed
 
[34]  Maeda Y.” Cell-cycle checkpoint for transition from cell division to differentiation”. Develop Growth Differ, 53:463-481. 2011.View Article  PubMed
 
[35]  Katto J, Mahlknecht U. “Epigenetic regulation of cellular adhesion in cancer”. Carcinogenesis, 32(10):1414-1418. Jun. 2011.View Article  PubMed
 
[36]  Klusza S, Deng WM. “At the crossroads of differentiation and proliferation: precise control of cell-cycle changes by multiples signaling pathways in Drosophila follicle cells”. Bioessays, 33(2):124-134. Feb. 2011.View Article  PubMed
 
[37]  Poulson ND, Lechler T. “Asymmetric cell divisions in the epidermis”. Int Rev Cell Mol Biol, 295:199-232. 2012.View Article  PubMed
 
[38]  Holmberg J and Perlmann. “Maintaining differentiated cellular identity”. Nat Rev Genet, 13 (6): 429-439. June 2012.View Article  PubMed
 
[39]  Enver T, Pera M, Peterson C, Andrew PW. “Stem cell states, fates and the rules of attraction”. Cell Stem Cell, 4(5):387-397. May. 2009.
 
[40]  Guo G, Huss M, Tong GQ, Wang C, Li Sun L, Clarke ND, Robson P. “Resolution of cell fate decisions revealed by single cell gene expression analysis from zygote or blastocyst”. Dev Cell, 18(4):675-685. Apr. 2010.View Article  PubMed
 
[41]  Hanna JH, Saha K, Jaenisch R.” Pluripotency and cellular reprogramming: facts, hyphoteses, unresolved issues”. Cell, 143 (4):508-524, Nov. 2010.View Article  PubMed
 
[42]  Li M, Liu GH, Izpisua BJC. “Navigating the epigenetic landscape of pluripotent stem cells”. Nat Rev Mol Cell Biol, 13(8):524-535, Aug. 2012.View Article  PubMed
 
[43]  Chin MH, Mason MJ, Xie W, Volinia S, Singer M, Peterson C, et al. “Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures”. Cell Stem Cell, 5(1):111-123. Jul. 2009.View Article  PubMed
 
[44]  Winkler T, Cantilena A, Metais JY, Xu X, Nguyen AD, Borate B, et al. “No evidence for clonal selection due to lentiviral integration sites in human induced pluripotent stem cells”. Stem Cells, 28(4):687-694. Apr. 2010.View Article  PubMed
 
[45]  Jopling C, Boue S, Izpisua JCB.” Dedifferentiation, transdifferentiation and reprogramming: three routes to regeneration”. Nat Rev Mol Cell Biol, 12(2):79-89. Feb. 2011.View Article  PubMed
 
[46]  Loh YH, Yang L, Yang JC, Li H, Collins JJ, Daley GQ.”Genomic approaches to deconstruct pluripotency”. Annu Rev Genomics Hum Genet, 12:165-185. Sep.2011.View Article  PubMed
 
[47]  Tachibana M, Amato P, Sparman M, Marti NG, Tippner-Hedges R, Ma H, Kang E, et al. “Human embryonic stem cells derived by somatic cell nuclear transfer”. Cell, 153:1-11. May. 2013.
 
[48]  Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, Lee TI, et al. “Polycomb complexes repress developmental regulators in murine embryonic stem cells”. Nature, 441 (7091):349-353. May. 2006.