SCD  Vol.5 No.1 , January 2015
An Insight on Small Molecule Induced Foot-Print Free Naive Pluripotent Stem Cells in Livestock
Bona fide embryonic stem cell (ESC) lines from livestock species have been challenging to derive and maintain, contrasting mouse and human ESCs. However, induced pluripotent stem cells (iPSC) generated by reprogramming somatic cells tender an option, as they display characteristic features of ESC. The comprehension that induced pluripotent stem cells (iPSC) could be created with in no time also holds the potential of allowing pluripotent cells to be derived from animal models vital in biomedical research. Endeavors to produce bona fide pluripotent stem cells (PSC) from livestock have been going on for more than two decades. But, attempts to derive bona fide livestock iPS cells have met with limited success. Recently it’s been reported that small molecules can augment reprogramming efficiency and may be used to substitute few or all transcription factors used for reprogramming. It is assumed that the reprogramming factors are conserved among species, and this small molecule reprogramming approach will probably apply to livestock species as well. So this review will focus mainly on the accomplishments of small molecules on accelerating cell reprogramming and obtaining naive pluripotency, and raise a new insight on, exogenous genes free, livestock naive iPSC generation with a new bullet, small molecule.

Cite this paper
Li, M. , Li, L. , Zhang, J. , Verma, V. , Liu, Q. , Shi, D. and Huang, B. (2015) An Insight on Small Molecule Induced Foot-Print Free Naive Pluripotent Stem Cells in Livestock. Stem Cell Discovery, 5, 1-9. doi: 10.4236/scd.2015.51001.
[1]   Nichols, J. and Smith, A. (2009) Naive and Primed Pluripotent States. Cell Stem Cell, 4, 487-492.

[2]   Gafni, O., Weinberger, L., Mansour, A.A., Manor, Y.S., Chomsky, E., Ben-Yosef, D., et al. (2013) Derivation of Novel Human Ground State Naive Pluripotent Stem Cells. Nature, 504, 282-286.

[3]   Hassani, S.N., Totonchi, M., Gourabi, H., Scholer, H.R. and Baharvand, H. (2014) Signaling Roadmap Modulating Naive and Primed Pluripotency. Stem Cells and Development, 23, 193-208.

[4]   Nowak-Imialek, M. and Niemann, H. (2013) Pluripotent Cells in Farm Animals: State of the Art and Future Perspectives. Reproduction Fertility and Development, 25, 103-128.

[5]   Zhao, Y., Lin, J., Wang, L., Chen, B., Zhou, C., Chen, T., et al. (2011) Derivation and Characterization of Ovine Embryonic Stem-Like Cell Lines in Semi-Defined Medium without Feeder Cells. Journal of Experimental Zoology Part A, Ecological Genetics and Physiology, 315, 639-648.

[6]   Liao, J., Cui, C., Chen, S., Ren, J., Chen, J., Gao, Y., et al. (2009) Generation of Induced Pluripotent Stem Cell Lines from Adult Rat Cells. Cell Stem Cell, 4, 11-15.

[7]   Huang, B., Li, T., Alonso-Gonzalez, L., Gorre, R., Keatley, S., Green, A., et al. (2011) A Virus-Free Poly-Promoter Vector Induces Pluripotency in Quiescent Bovine Cells under Chemically Defined Conditions of Dual Kinase Inhibition. PLoS One, 6, e24501.

[8]   Nagy, K., Sung, H.K., Zhang, P., Laflamme, S., Vincent, P., Agha-Mohammadi, S., et al. (2011) Induced Pluripotent Stem Cell Lines Derived from Equine Fibroblasts. Stem Cell Reviews, 7, 693-702.

[9]   Deng, Y., Liu, Q., Luo, C., Chen, S., Li, X., Wang, C., et al. (2012) Generation of Induced Pluripotent Stem Cells From Buffalo [Bubalus bubalis] Fetal Fi-broblasts with Buffalo Defined Factors. Stem Cells and Development, 21, 2485-2494.

[10]   Liu, J., Balehosur, D., Murray, B., Kelly, J.M., Sumer, H. and Verma, P.J. (2012) Generation and Characterization of Reprogrammed Sheep Induced Pluripotent Stem Cells. Theriogenology, 77, 338-346.

[11]   Song, H., Li, H., Huang, M., Xu, D., Gu, C., Wang, Z., et al. (2013) Induced Pluripotent Stem Cells from Goat Fibroblasts. Molecular Reproduction and Development, 80, 1009-1017.

[12]   West, F.D., Uhl, E.W., Liu, Y., Stowe, H., Lu, Y., Yu, P., et al. (2011) Brief Report: Chimeric Pigs Produced from Induced Pluripotent Stem Cells Demonstrate Germline Transmission and No Evidence of Tumor Formation in Young Pigs. Stem Cells, 29, 1640-1643.

[13]   Fan, N., Chen, J., Shang, Z., Dou, H., Ji, G., Zou, Q., et al. (2013) Piglets Cloned from Induced Pluripotent Stem Cells. Cell Research, 23, 162-166.

[14]   McLaren, A. (2000) Cloning: Pathways to a Pluripotent Future. Science, 288, 1775-1780.

[15]   Do, J.T. and Scholer, H.R. (2004) Nuclei of Embryonic Stem Cells Reprogram Somatic Cells. Stem Cells, 22, 941-949.

[16]   Takahashi, K. and Yamanaka, S. (2006) Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors. Cell, 126, 663-676.

[17]   Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., et al. (2007) Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors. Cell, 131, 861-872.

[18]   Hamanaka, S., Yamaguchi, T., Kobayashi, T., Kato-Itoh, M., Yamazaki, S., Sato, H., et al. (2011) Generation of Germline-Competent Rat Induced Pluripotent Stem Cells. PlOS One, 6, e22008.

[19]   Osteil, P., Tapponnier, Y., Markossian, S., Godet, M., Schmaltz-Panneau, B., Jouneau, L., et al. (2013) Induced Pluripotent Stem Cells Derived from Rabbits Exhibit Some Characteristics of Naive Pluripotency. Biology Open, 2, 613-628.

[20]   Inoue, H., Nagata, N., Kurokawa, H. and Yamanaka, S. (2014) iPS Cells: A Game Changer for Future Medicine. The EMBO Journal, 33, 409-417.

[21]   Suh, J.H., Kim, D., Kim, H., Helfman, D.M., Choi, J.H., Lee, B.H., et al. (2014) Modeling of Menkes Disease via Human Induced Pluripotent Stem Cells. Biochemical and Biophysical Research Communications, 444, 311-318.

[22]   Miao, X. (2013) Recent Advances in the Development of New Transgenic Animal Technology. Cellular and Molecular Life Sciences, 70, 815-828.

[23]   Yu, J., Vodyanik, M.A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J.L., Tian, S., et al. (2007) Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells. Science, 318, 1917-1920.

[24]   Huangfu, D., Maehr, R., Guo, W., Eijkelenboom, A., Snitow, M., Chen, A.E., et al. (2008) Induction of Pluripotent Stem Cells by Defined Factors Is Greatly Improved by Small-Molecule Compounds. Nature biotechnology, 26, 795-797.

[25]   Stadtfeld, M., Nagaya, M., Utikal, J., Weir, G. and Hochedlinger, K. (2008) Induced Pluripotent Stem Cells Generated without Viral Integration. Science, 322, 945-949.

[26]   Ma, K., Song, G., An, X., Fan, A., Tan, W., Tang, B., et al. (2014) miRNAs Promote Generation of Porcine-Induced Pluripotent Stem Cells. Molecular and Cellular Biochemistry, 389, 209-218

[27]   Kim, D., Kim, C.H., Moon, J.I., Chung, Y.G., Chang, M.Y., Han, B.S., et al. (2009) Generation of Human Induced Pluripotent Stem Cells by Direct Delivery of Re-programming Proteins. Cell Stem Cell, 4, 472-476.

[28]   Hou, P., Li, Y., Zhang, X., Liu, C., Guan, J., Li, H., et al. (2013) Pluripotent Stem Cells Induced from Mouse Somatic Cells by Small-Molecule Compounds. Science, 341, 651-654.

[29]   Su, J.B., Pei, D.Q. and Qin, B.M. (2013) Roles of Small Molecules in Somatic Cell Reprogramming. Acta Pharmacologica Sinica, 34, 719-724.

[30]   Jung, D.W., Kim, W.H. and Williams, D.R. (2014) Reprogram or Reboot: Small Molecule Approaches for the Production of Induced Pluripotent Stem Cells and Direct Cell Reprogramming. ACS Chemical Biology, 9, 80-95.

[31]   Li, W., Jiang, K., Wei, W., Shi, Y. and Ding, S. (2013) Chemical Approaches to Studying Stem Cell Biology. Cell Research, 23, 81-91.

[32]   Li, W., Wei, W., Zhu, S., Zhu, J., Shi, Y., Lin, T., et al. (2009) Generation of Rat and Human Induced Pluripotent Stem Cells by Combining Genetic Reprogramming and Chemical Inhibitors. Cell Stem Cell, 4, 16-19.

[33]   Lin, T., Ambasudhan, R., Yuan, X., Li, W., Hilcove, S., Abujarour, R., et al. (2009) A Chemical Platform for Improved Induction of Human iPSCs. Nature Methods, 6, 805-808.

[34]   Gross, B., Sgodda, M., Rasche, M., Schambach, A., Gohring, G., Schlegelberger, B., et al. (2013) Improved Generation of Patient-Specific Induced Pluripotent Stem Cells Using a Chemically-Defined and Matrigel-Based Approach. Current Molecular Medicine, 13, 765-776.

[35]   Grace, A., McMillan, M., Schmoelzl, S. and Hinch, G. (2013) 187 Increased Efficiency of Deriving Bovine Stem Cell-Like Colonies Using Valproic Acid and Small Molecule Cocktails. Reproduction, Fertility and Development, 26, 208.

[36]   Shi, Y., Desponts, C., Do, J.T., Hahm, H.S., Scholer, H.R. and Ding, S. (2008) Induction of Pluripotent Stem Cells from Mouse Embryonic Fibroblasts by Oct4 and Klf4 with Small-Molecule Compounds. Cell Stem Cell, 3, 568-774.

[37]   Zhu, S., Li, W., Zhou, H., Wei, W., Ambasudhan, R., Lin, T., et al. (2010) Reprogramming of Human Primary Somatic Cells by OCT4 and Chemical Compounds. Cell Stem Cell, 7, 651-655.

[38]   Trokovic, R., Weltner, J., Manninen, T., Mikkola, M., Lundin, K., Hamalainen, R., et al. (2013) Small Molecule Inhibitors Promote Efficient Generation of Induced Pluripotent Stem Cells from Human Skeletal Myoblasts. Stem Cells and Development, 22, 114-123.

[39]   Wang, Q., Xu, X., Li, J., Liu, J., Gu, H., Zhang, R., et al. (2011) Lithium, an Anti-Psychotic Drug, Greatly Enhances the Generation of Induced Pluripotent Stem Cells. Cell Research, 21, 1424-1435.

[40]   Xu, X., Wang, Q., Long, Y., Zhang, R., Wei, X., Xing, M., et al. (2013) Stress-Mediated p38 Activation Promotes Somatic Cell Reprogramming. Cell Research, 23, 131-141.

[41]   Wei, X., Chen, Y., Xu, Y., Zhan, Y., Zhang, R., Wang, M., et al. (2014) Small Molecule Compound Induces Chromatin De-Condensation and Facilitates Induced Pluripotent Stem Cell Generation. Journal of Molecular Cell Biology, 6, 409-420.

[42]   Ichida, J.K., Blanchard, J., Lam, K., Son, E.Y., Chung, J.E., Egli, D., et al. (2009) A Small-Molecule Inhibitor of Tgf-β Signaling Replaces Sox2 in Reprogramming by Inducing Nanog. Cell Stem Cell, 5, 491-503.

[43]   Staerk, J., Lyssiotis, C.A., Medeiro, L.A., Bollong, M., Foreman, R.K., Zhu, S., et al. (2011) Pan-Src Family Kinase Inhibitors Replace Sox2 during the Direct Reprogramming of Somatic Cells. Angewandte Chemie International Edition, 50, 5734-5736.

[44]   Lyssiotis, C.A., Foreman, R.K., Staerk, J., Garcia, M., Mathur, D., Markoulaki, S., et al. (2009) Reprogramming of Murine Fibroblasts to Induced Pluripotent Stem Cells with Chemical Complementation of Klf4. Proceedings of the National Academy of Sciences, 106, 8912-8917.

[45]   Huangfu, D., Osafune, K., Maehr, R., Guo, W., Eijkelenboom, A., Chen, S., et al. (2008) Induction of Pluripotent Stem Cells from Primary Human Fibroblasts with Only Oct4 and Sox2. Nature Biotechnology, 26, 1269-1275.

[46]   Sui, D., Sun, Z., Xu, C., Wu, Y., Capecchi, M.R., Wu, S., et al. (2014) Fine-Tuning of iPSC Derivation by an Inducible Reprogramming System at the Protein Level. Stem Cell Reports, 2, 21-33.

[47]   Li, Y., Zhang, Q., Yin, X., Yang, W., Du, Y., Hou, P., et al. (2011) Generation of iPSCs from Mouse Fibroblasts with a Single Gene, Oct4, and Small Molecules. Cell Research, 21, 196-204.

[48]   Yuan, X., Wan, H., Zhao, X., Zhu, S., Zhou, Q. and Ding, S. (2011) Brief Report: Combined Chemical Treatment Enables Oct4-Induced Reprogramming from Mouse Embryonic Fibroblasts. Stem Cells, 29, 549-553.

[49]   Kang, P.J., Moon, J.H., Yoon, B.S., Hyeon, S., Jun, E.K., Park, G., et al. (2014) Reprogramming of Mouse Somatic Cells into Pluripotent Stem-Like Cells Using a Combination of Small Molecules. Biomaterials, 35, 336-345.

[50]   Ying, Q.L., Wray, J., Nichols, J., Batlle-Morera, L., Doble, B., Woodgett, J., et al. (2008) The Ground State of Embryonic Stem Cell Self-Renewal. Nature, 453, 519-523.

[51]   Hirano, K., Nagata, S., Yamaguchi, S., Nakagawa, M., Okita, K., Kotera, H., et al. (2012) Human and Mouse Induced Pluripotent Stem Cells Are Differentially Reprogrammed in Response to Kinase Inhibitors. Stem Cells and Development, 21, 1287-1298.

[52]   Leitch, H.G., McEwen, K.R., Turp, A., Encheva, V., Carroll, T., Grabole, N., et al. (2013) Naive Pluripotency Is Associated with Global DNA Hypomethylation. Nature Structural & Molecular Biology, 20, 311-316.

[53]   Yamaji, M., Ueda, J., Hayashi, K., Ohta, H., Yabuta, Y., Kurimoto, K., et al. (2013) PRDM14 Ensures Naive Pluripotency through Dual Regulation of Signaling and Epigenetic Pathways in Mouse Embryonic Stem Cells. Cell Stem Cell, 12, 368-382.

[54]   Buehr, M., Meek, S., Blair, K., Yang, J., Ure, J., Silva, J., et al. (2008) Capture of Authentic Embryonic Stem Cells from Rat Blastocysts. Cell, 135, 1287-1298.

[55]   Li, P., Tong, C., Mehrian-Shai, R., Jia, L., Wu, N., Yan, Y., et al. (2008) Germline Competent Embryonic Stem Cells Derived from Rat Blastocysts. Cell, 135, 1299-1310.

[56]   Leitch, H.G., Blair, K., Mansfield, W., Ayetey, H., Humphreys, P., Nichols, J., et al. (2010) Embryonic Germ Cells from Mice and Rats Exhibit Properties Consistent with a Generic Pluripotent Ground State. Development, 137, 2279-2287.

[57]   Blair, K., Leitch, H.G., Mansfield, W., Dumeau, C.E., Humphreys, P. and Smith, A.G. (2012) Culture Parameters for Stable Expansion, Genetic Modification and Germline Transmission of Rat Pluripotent Stem Cells. Biology Open, 1, 58-65.

[58]   Ten Berge, D., Kurek, D., Blauwkamp, T., Koole, W., Maas, A., Eroglu, E., et al. (2011) Embryonic Stem Cells Require Wnt Proteins to Prevent Differentiation to Epiblast Stem Cells. Nature Cell Biology, 13, 1070-1075.

[59]   Kinehara, M., Kawamura, S., Tateyama, D., Suga, M., Matsumura, H., Mimura, S., et al. (2013) Protein Kinase C Regulates Human Pluripotent Stem Cell Self-Renewal. PlOS One, 8, e54122.

[60]   Zhou, H., Li, W., Zhu, S., Joo, J.Y, Do, J.T., Xiong, W., et al. (2010) Conversion of Mouse Epiblast Stem Cells to an Earlier Pluripotency State by Small Molecules. Journal of Biological Chemistry, 285, 29676-29680.

[61]   Kang, S.J., Park, Y.I., So, B. and Kang, H.G. (2014) Sodium Butyrate Efficiently Converts Fully Reprogrammed Induced Pluripotent Stem Cells from Mouse Partially Reprogrammed Cells. Cellular Reprogramming, 16, 345-354.

[62]   Baharvand, H. and Hassani, S.N. (2013) A New Chemical Approach to the Efficient Generation of Mouse Embryonic Stem Cells. Methods in Molecular Biology, 997, 13-22.

[63]   Rodriguez, A., Allegrucci, C. and Alberio, R. (2012) Modulation of Pluripotency in the Porcine Embryo and iPS Cells. PLOS One, 7, e49079.

[64]   Gao, Y., Guo, Y., Duan, A., Cheng, D., Zhang, S. and Wang, H. (2014) Optimization of Culture Conditions for Maintaining Porcine Induced Pluripotent Stem Cells. DNA and Cell Biology, 33, 1-11.

[65]   Zhang, Y., Wei, C., Zhang, P., Li, X., Liu, T., Pu, Y., et al. (2014) Efficient Reprogramming of Naive-Like Induced Pluripotent Stem Cells from Porcine Adipose-Derived Stem Cells with a Feeder-Independent and Serum-Free System. PLOS One, 9, e85089.

[66]   Sharma, R., George, A., Kamble, N.M., Singh, K.P., Chauhan, M.S., Singla, S.K., et al. (2011) Optimization of Culture Conditions to Support Long-Term Self-Renewal of Buffalo (Bubalus bubalis) Embryonic Stem Cell-Like Cells. Cell Reprogramming, 13, 539-549.

[67]   Sharma, R., George, A., Chauhan, M.S., Singla, S., Manik, R.S. and Palta, P. (2013) ROCK Inhibitor Y-27632 Enhances the Survivability of Dissociated Buffalo (Bubalus bubalis) Embryonic Stem Cell-Like Cells. Reproduction, Fertility and Development, 25, 446-455.

[68]   Sharma, R., Kamble, N.M., George, A., Chauhan, M.S., Singla, S., Manik, R.S., et al. (2013) Effect of TGF-β1 Superfamily Members on Survival of Buffalo (Bubalus bubalis) Embryonic Stem-Like Cells. Reproduction in Domestic Animals, 48, 569-576.

[69]   Harris, D., Huang, B. and Oback, B. (2013) Inhibition of MAP2K and GSK3 Signaling Promotes Bovine Blastocyst Development and Epiblast-Associated Expression of Pluripotency Factors. Biology of Reproduction, 88, 74.

[70]   Verma, V., Huang, B., Kallingappa, P.K. and Oback, B. (2013) Dual Kinase Inhibition Promotes Pluripotency in Finite Bovine Embryonic Cell Lines. Stem Cells and Development, 22, 1728-1742.

[71]   Lu, F., Lao, Y., Sun, H., Lei, C., Deng, Y., Luo, C., et al. (2013) 195 Effects of Gsk3 Inhibitor on the Pluripotency Maintenance of Buffalo Embryonic Stem-Cell-Like Cells. Reproduction, Fertility and Development, 26, 212.