Login Register Cart 0
Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Suppression of TGF-β and ERK Signaling Pathways as a New Strategy to Provide Rodent and Non-Rodent Pluripotent Stem Cells

Author(s): Maryam Farzaneh, Zahra Derakhshan, Jamal Hallajzadeh, Neda Hosseini Sarani, Armin Nejabatdoust and Seyed Esmaeil Khoshnam*

Volume 14, Issue 6, 2019

Page: [466 - 473] Pages: 8

DOI: 10.2174/1871527318666190314110529

Price: $65

Abstract

Stem cells are unspecialized cells and excellent model in developmental biology and a promising approach to the treatment of disease and injury. In the last 30 years, pluripotent embryonic stem (ES) cells were established from murine and primate sources, and display indefinite replicative potential and the ability to differentiate to all three embryonic germ layers. Despite large efforts in many aspects of rodent and non-rodent pluripotent stem cell culture, a number of diverse challenges remain. Natural and synthetic small molecules (SMs) strategy has the potential to overcome these hurdles. Small molecules are typically fast and reversible that target specific signaling pathways, epigenetic processes and other cellular processes. Inhibition of the transforming growth factor-β (TGF-β/Smad) and fibroblast growth factor 4 (FGF4)/ERK signaling pathways by SB431542 and PD0325901 small molecules, respectively, known as R2i, enhances the efficiency of mouse, rat, and chicken pluripotent stem cells passaging from different genetic backgrounds. Therefore, the application of SM inhibitors of TGF-β and ERK1/2 with leukemia inhibitory factor (LIF) allows the cultivation of pluripotent stem cells in a chemically defined condition. In this review, we discuss recently emerging evidence that dual inhibition of TGF-β and FGF signaling pathways plays an important role in regulating pluripotency in both rodent and non-rodent pluripotent stem cells.

Keywords: Stem cells, small molecules, TGF-β/Smad pathway, FGF4/ERK pathway, chemically defined condition, Pluripotent Stem Cells.

« Previous Next »
[1]
Li W, Ding S. Small molecules that modulate embryonic stem cell fate and somatic cell reprogramming. Trends Pharmacol Sci 2010; 31: 36-45.
[2]
Watt FM, Hogan BL. Out of Eden: Stem cells and their niches. Science 2000; 287: 1427-30.
[3]
Martin GR. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci 1981; 78: 7634-8.
[4]
Carpenter M, Rosler E, Rao M. Characterization and differentiation of human embryonic stem cells. Cloning Stem Cells 2003; 5: 79-88.
[5]
Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature 1981; 292: 154.
[6]
Kress C, Vandormael-Pournin S, Baldacci P, Cohen-Tannoudji M, Babinet C. Nonpermissiveness for mouse embryonic stem (ES) cell derivation circumvented by a single backcross to 129/Sv strain: Establishment of ES cell lines bearing the Om d conditional lethal mutation. Mamm Genome 1998; 9: 998-1001.
[7]
Hassani S-N, Totonchi M, Farrokhi A, et al. Simultaneous suppression of TGF-β and ERK signaling contributes to the highly efficient and reproducible generation of mouse embryonic stem cells from previously considered refractory and non-permissive strains. Stem Cell Rev Rep 2012; 8: 472-81.
[8]
Farzaneh M, Zare M, Hassani SN, Baharvand H. Effects of various culture conditions on pluripotent stem cell derivation from chick embryos. J Cell Biochem 2018; 119(8): 6325-36.
[9]
Farzaneh M, Attari F, Mozdziak P, Khoshnam S. The evolution of chicken stem cell culture methods. Brit Poultry Sci 2017; 58: 681-6.
[10]
Schugar R, Robbins P, Deasy B. Small molecules in stem cell self-renewal and differentiation. Gene Ther 2008; 15: 126.
[11]
Zhang Y, Li W, Laurent T, Ding S. Small molecules, big roles–the chemical manipulation of stem cell fate and somatic cell reprogramming. J Cell Sci 2012; 125: 5609-20.
[12]
Ying Q-L, Wray J, Nichols J, et al. The ground state of embryonic stem cell self-renewal. Nature 2008; 453: 519.
[13]
Hanna J, Markoulaki S, Mitalipova M, et al. Metastable pluripotent states in NOD-mouse-derived ESCs. Cell Stem Cell 2009; 4: 513-24.
[14]
Wray J, Kalkan T, Smith AG. Portland Press Limited 2010.
[15]
Valvezan AJ, Zhang F, Diehl JA, Klein PS. Adenomatous polyposis coli (APC) regulates multiple signaling pathways by enhancing glycogen synthase kinase-3 (GSK-3) activity. J Biol Chem 2012; 287: 3823-32.
[16]
Acevedo N, Wang X, Dunn RL, Smith GD. Glycogen synthase kinase‐3 regulation of chromatin segregation and cytokinesis in mouse preimplantation embryos. Mol Rep Dev Gamete Res 2007; 74: 178-88.
[17]
Jacobs KM, Bhave SR, Ferraro DJ, Jaboin JJ, Hallahan DE, Thotala D. GSK-3. Int J Cell Biol 2012; 2012930710
[18]
Beurel E, Grieco SF, Jope RS. Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases. Pharmacol Ther 2015; 148: 114-31.
[19]
Hassani S-N, Totonchi M, Sharifi-Zarchi A, et al. Inhibition of TGFβ signaling promotes ground state pluripotency. Stem Cell Rev Rep 2014; 10: 16-30.
[20]
Attari F, Sepehri H, Ansari H, et al. Efficient induction of pluripotency in primordial germ cells by dual inhibition of TGF-β and ERK signaling pathways. Stem Cells Dev 2014; 23: 1050-61.
[21]
Mohammadi A, Attari F, Babapour V, et al. Generation of Rat Embryonic Germ Cells via Inhibition of TGFß and MEK Pathways. Cell J (Yakhteh) 2015; 17: 288.
[22]
Matsuda T, Nakamura T, Nakao K, et al. STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells. EMBO J 1999; 18: 4261-9.
[23]
Ohtsuka S, Nakai-Futatsugi Y, Niwa H. LIF signal in mouse embryonic stem cells. JAK-STAT 2015; 4: 1-9.
[24]
Caron E, Ghosh S, Matsuoka Y, et al. A comprehensive map of the mTOR signaling network. Mol Syst Biol 2010; 6: 453.
[25]
Kaur A, Sharma S. Mammalian target of rapamycin (mTOR) as a potential therapeutic target in various diseases. Inflammopharmacology 2017; 25: 293-312.
[26]
Cherepkova MY, Sineva GS, Pospelov VA. Leukemia inhibitory factor (LIF) withdrawal activates mTOR signaling pathway in mouse embryonic stem cells through the MEK/ERK/TSC2 pathway. Cell Death Dis 2016; 7: e2050-0.
[27]
Ying Q-L, Nichols J, Chambers I, Smith A. BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell 2003; 115: 281-92.
[28]
Lanner F, Rossant J. The role of FGF/Erk signaling in pluripotent cells. Development 2010; 137: 3351-60.
[29]
Hamilton WB, Brickman JM. Erk signaling suppresses embryonic stem cell self-renewal to specify endoderm. Cell Rep 2014; 9: 2056-70.
[30]
Ornitz DM, Itoh N. The fibroblast growth factor signaling pathway. Wiley Interdiscip Rev Dev Biol 2015; 4: 215-66.
[31]
Hassani S-N, Totonchi M, Gourabi H, Schöler HR, Baharvand H. Signaling roadmap modulating naive and primed pluripotency. Stem Cells Dev 2013; 23: 193-208.
[32]
Coutu DL, Galipeau J. Roles of FGF signaling in stem cell self-renewal, senescence and aging. Aging (Albany NY) 2011; 3: 920.
[33]
Arkin MR, Wells JA. Small-molecule inhibitors of protein–protein interactions: progressing towards the dream. Nat Rev Drug Discov 2004; 3: 301.
[34]
Wu P-K, Park J-I. Seminars in oncology. Elsevier 2015; pp. 849-62.
[35]
Tighe A, Ray-Sinha A, Staples OD, Taylor SS. GSK-3 inhibitors induce chromosome instability. BMC Cell Biol 2007; 8: 34.
[36]
Bock AS, Leigh ND, Bryda EC. Effect of Gsk3 inhibitor CHIR99021 on aneuploidy levels in rat embryonic stem cells. In Vitro Cell Dev Biol Anim 2014; 50: 572-9.
[37]
Halder SK, Beauchamp RD, Datta PK. A specific inhibitor of TGF-β receptor kinase, SB-431542, as a potent antitumor agent for human cancers. Neoplasia 2005; 7: 509-21.
[38]
Park K-S. Tgf-Beta family signaling in embryonic stem cells. Int J Stem Cells 2011; 4: 18.
[39]
Hinck AP. Structural studies of the TGF‐βs and their receptors–insights into evolution of the TGF‐β superfamily. FEBS Lett 2012; 586: 1860-70.
[40]
Huang T, Hinck AP. Production, isolation, and structural analysis of ligands and receptors of the TGF-β superfamily, TGF-β Signaling. Methods Mol Biol 2016; 1344: 63-92.
[41]
Nickel J, ten Dijke P, Mueller TD. TGF-β family co-receptor function and signaling. Acta Biochim et Biophys Sin 2017; 50: 12-36.
[42]
Budi EH, Duan D, Derynck R. Transforming growth factor-β receptors and Smads: regulatory complexity and functional versatility. Trends Cell Biol 2017; 27: 658-72.
[43]
Inman GJ, Nicolás FJ, Callahan JF, et al. SB-431542 is a potent and specific inhibitor of transforming growth factor-β superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Mol Pharmacol 2002; 62: 65-74.
[44]
Hassani S-N, Pakzad M, Asgari B, Taei A, Baharvand H. Suppression of transforming growth factor β signaling promotes ground state pluripotency from single blastomeres. Human Reprod 2014; 29: 1739-48.
[45]
Saitou M. Germ cell specification in mice. Curr Opin Genet Dev 2009; 19: 386-95.
[46]
Eguizabal C, Shovlin TC, Durcova-Hills G, Surani A, McLaren A. Generation of primordial germ cells from pluripotent stem cells. Differentiation 2009; 78: 116-23.
[47]
Felici MD, Farini D, Dolci S. In or out stemness: Comparing growth factor signalling in mouse embryonic stem cells and primordial germ cells. Curr Stem Cell Res Ther 2009; 4: 87-97.
[48]
De Felici M. Nuclear reprogramming in mouse primordial germ cells: epigenetic contribution. Stem Cells Int 2011; 2011425863
[49]
Durcova-Hills G, Ainscough JF-X, McLaren A. Pluripotential stem cells derived from migrating primordial germ cells. Differentiation 2001; 68: 220-6.
[50]
Tada T, Tada M, Hilton K, et al. Epigenotype switching of imprintable loci in embryonic germ cells. Dev Genes Evol 1998; 207: 551-61.
[51]
Leitch HG, Blair K, Mansfield W, et al. Embryonic germ cells from mice and rats exhibit properties consistent with a generic pluripotent ground state. Development 2010; 137(14): 2279-87.
[52]
Medina M, Wandosell F. Deconstructing GSK-3: The fine regulation of its activity. Int J Alzheimers Dis 2011; 2011479249
[53]
Farzaneh M, Attari F, Khoshnam S, Mozdziak P. The method of chicken whole embryo culture using the eggshell windowing, surrogate eggshell and ex ovo culture system. Br Poult Sci 2018; 59: 240-4.
[54]
Farzaneh M, Khoshnam SE, Nokhbatolfoghahai M. First scientific record of two cases of partial twinning in the chick embryo, Gallus gallus domesticus. Veteri Record Case Rep 2016; 4e000353
[55]
Farzaneh M, Hassani SN, Mozdziak P, Baharvand H. Avian embryos and related cell lines: A convenient platform for recombinant proteins and vaccine production. Biotechnolo J 2017; 121600598
[56]
Farzaneh M, Khoshnam S, Mozdziak P. Concise review: Avian multipotent stem cells as a novel tool for investigating cell-based therapies. J Dairy Vet Anim Res 2017; 5: 00125.
[57]
Whyte J, Glover JD, Woodcock M, et al. FGF, insulin, and SMAD signaling cooperate for avian primordial germ cell self-renewal. Stem Cell Rep 2015; 5: 1171-82.
[58]
Collarini EJ, Leighton PA, Van de Lavoir M-C. Production of transgenic chickens using cultured primordial germ cells and gonocytes, microinjection. Springer 2019; pp. 403-30.
[59]
Hwang YS, Han JY. Transgenesis and Genome Editing in Poultry. Appl Genetics Genomics Poult Sci IntechOpen 2018.
[60]
Li R, Tang X, Xu S, et al. SC1 sustains the self‐renewal capacity and pluripotency of chicken blastodermal cells by inhibiting the phosphorylation of ERK1 and promoting the phosphorylation of Akt. Reprod Domest Anim 2018; 53: 1052-9.
[61]
Pamonsinlapatham P, Hadj-Slimane R, Lepelletier Y, et al. p120-Ras GTPase activating protein (RasGAP): A multi-interacting protein in downstream signaling. Biochimie 2009; 91: 320-8.
[62]
Noli L, Ogilvie C, Khalaf Y, Ilic D. Potential of human twin embryos generated by embryo splitting in assisted reproduction and research. Hum Reprod 2016; 23: 156-65.
[63]
Vajta G, Peura T, Holm P, et al. New method for culture of zona‐included or zona‐free embryos: The Well of the Well (WOW) system. Molecular reproduction and development: Incorporating gamete research. Hum Reprod 2000; 55: 256-64.
[64]
Swain J, Smith G. Advances in embryo culture platforms: Novel approaches to improve preimplantation embryo development through modifications of the microenvironment. Hum Reprod 2011; 17: 541-57.
[65]
Jayamohan H, Romanov V, Li H, et al. Advances in Microfluidics and Lab-on-a-Chip Technologies, Mol Diagn. (Third Edition). Elsevier 2017; pp. 197-217.
[66]
Saliba J, Daou A, Damiati S, Saliba J, El-Sabban M, Mhanna R. Development of microplatforms to mimic the in vivo architecture of CNS and PNS physiology and their diseases. Genes 2018; 9: 285.
[67]
Heo Y, Cabrera L, Bormann C, Shah C, Takayama S, Smith G. Dynamic microfunnel culture enhances mouse embryo development and pregnancy rates. Hum Reprod 2010; 25: 613-22.
[68]
Yekani F, Fazel‐Tabar M, Kowsari‐Esfahan R, et al. Enhancing developmental rate and quality of mouse single blastomeres into blastocysts using a microplatform. J Cell Physiol 2018; 233: 9070-6.
[69]
Yekani F, Azarnia M, Esfandiari F, Hassani SN, Baharvand H. Enhanced development of mouse single blastomeres into blastocysts via the simultaneous inhibition of TGF‐β and ERK pathways in microdroplet culture. J Cell Biochem 2018; 119(9): 7621-30.
[70]
Yu S, Ma H, Ow JR, et al. Zfp553 Is Essential for Maintenance and Acquisition of Pluripotency. Stem Cells Dev 2015; 25: 55-67.
[71]
Farzaneh M, Attari F, Khoshnam SE. Concise review: LIN28/let-7 signaling, a critical double-negative feedback loop during pluripotency, reprogramming, and Tumorigenicity. Cell Reprogram 2017; 19: 289-93.
[72]
Taleahmad S, Hassani SN, Hosseini GS, Baharvand H. Metabolic Signature of Pluripotent Stem Cells. Cell J 2018; 20: 388-95.
[73]
Dahan P, Lu V, Nguyen RM, Kennedy SA, Teitell MA. Metabolism in pluripotency: Both driver and passenger? J Biol Chem 2019; 294(14): 5420-9.
[74]
Hassani S-N, Moradi S, Taleahmad S, Braun T, Baharvand H. Transition of inner cell mass to embryonic stem cells: Mechanisms, facts, and hypotheses. Cell Mol Life Sci 2019; 76(5): 873-92.
[75]
Smith AG, Heath JK, Donaldson DD, et al. Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature 1988; 336: 688.
[76]
Gu W, Gaeta X, Sahakyan A, et al. Glycolytic metabolism plays a functional role in regulating human pluripotent stem cell state. Cell Stem Cell 2016; 19: 476-90.
[77]
Shyh-Chang N, Daley GQ. Metabolic switches linked to pluripotency and embryonic stem cell differentiation. Cell Metab 2015; 21: 349-50.
[78]
Lu C-W, Lin S-C, Chen K-F, Lai Y-Y, Tsai S-J. Induction of pyruvate dehydrogenase kinase-3 by hypoxia-inducible factor-1 promotes metabolic switch and drug resistance. J Biol Chem 2008; 283: 28106-14.
[79]
Varum S, Rodrigues AS, et al. Energy metabolism in human pluripotent stem cells and their differentiated counterparts. PloS One 2011; 6e20914
[80]
Zhao X, Guan J-L. Focal adhesion kinase and its signaling pathways in cell migration and angiogenesis. Adv Drug Deliv Rev 2011; 63: 610-5.
[81]
Taleahmad S, Mirzaei M, Samadian A, et al. Low focal adhesion signaling promotes ground state pluripotency of mouse embryonic stem cells. J Proteome Res 2017; 16: 3585-95.
[82]
Zhang K, Xu M, Su J, et al. Characterization and identification of the integrin family in silkworm, Bombyx mori. Gene 2014; 549: 149-55.
[83]
Totonchi M, Hassani S-N, Sharifi-Zarchi A, et al. Blockage of the epithelial-to-mesenchymal transition is required for embryonic stem cell derivation. Stem Cell Reports 2017; 9: 1275-90.
[84]
Khoshnam SE, Winlow W, Farzaneh M, Farbood Y, Moghaddam HF. Pathogenic mechanisms following ischemic stroke. Neurol Sci 2017; 38: 1167-86.
[85]
Khoshnam SE, Winlow W, Farbood Y, Moghaddam HF, Farzaneh M. Emerging roles of microRNAs in ischemic stroke: As possible therapeutic agents. J Stroke 2017; 19: 166.
[86]
Khoshnam SE, Winlow W, Farzaneh M. The interplay of MicroRNAs in the inflammatory mechanisms following ischemic stroke. J Neuropathol Exp Neurol 2017; 76: 548-61.
[87]
Guo L, Zhang H, Zhao Y, Yang S, Chen F. In-depth exploration of miRNA: A new approach to study miRNA at the miRNA/isomiR levels. Curr Bioinformatics 2014; 9: 522-30.
[88]
Shim J, Nam J-W. The expression and functional roles of microRNAs in stem cell differentiation. BMB Reports 2016; 49: 3.
[89]
Tiscornia G, Belmonte JCI. MicroRNAs in embryonic stem cell function and fate. Genes Development 2010; 24: 2732-41.
[90]
Farzaneh M, Alishahi M, Derakhshan Z, Sarani NH, Attari F, Khoshnam SE. The expression and functional roles of miRNAs in embryonic and lineage-specific stem cells. Curr Stem Cell Res Ther 2019; 14(3): 278-89.
[91]
Gunaratne PH. Embryonic stem cell microRNAs: Defining factors in induced pluripotent (iPS) and cancer (CSC) stem cells? Curr Stem Cell Res Ther 2009; 4: 168-77.
[92]
Moradi S, Sharifi-Zarchi A, Ahmadi A, et al. Small RNA Sequencing Reveals Dlk1-Dio3 Locus-Embedded MicroRNAs as Major Drivers of Ground-State Pluripotency. Stem Cell Reports 2017; 9: 2081-96.
[93]
Moradi S, Braun T, Baharvand H. miR-302b-3p Promotes Self-Renewal Properties in Leukemia Inhibitory Factor-Withdrawn Embryonic Stem Cells. Cell J (Yakhteh) 2018; 20: 61.

Rights & Permissions Print Cite
Article Metrics
56
2
© 2024 Bentham Science Publishers | Privacy Policy