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细胞重编程是将特定类型细胞转化成其他细胞类型。尤其是直接重编程体细胞，比如成纤维细胞转化成多能细胞，比如诱导性多能干细胞，或者iPS细胞。2006年，干细胞研究领域出现了革命性的发现。逆转录病毒载体过表达小鼠4种转录因子Oct4, Sox2, Klf4, 和c-Myc(mOSKM)，将小鼠胚胎成纤维部分重编程成为诱导性多能干细胞(iPS) (Takahashi 和Yamanaka 2006).接下来其他实验室制备了完全重编程的小鼠iPS细胞系，这些细胞实验证实具有小鼠胚胎干细胞(ES细胞)相当功能，能够形成嵌合小鼠(Wernig et al 2007)。相应的，重编程也可以在人细胞_上操作。使用hOSKM转录因子(Yamanaka 2007)或者使用一套因子组合( 用Nanog和Lin28代替KIf4和c-Myc )(Thomson 2007)可以制备iPS。
◆重编程的发展历程
重编程技术和递送技术近年来迅速发展，现在已经可以采用多种方法递送和表达必要的重编程因子进行直接重编程。这些方法包括整合逆转录和慢病毒载体，dox诱导表达系统和减少或者去除插入到宿主细胞基因组的瞬时或者可割取的方法。最近突破性的技术是在2010年9月干细胞会议上发布的修饰合成mRNAs，可以高效的进行人成纤维细胞的重编程，基因组不会发生改变。该项学术研究加速了其他策略的发展，会有更多的研究成果。
细胞重编程 指南目录
1.什么是细胞重编程
2.细胞重编程概述
3.mRNA重编程
4.病毒重编程
5.产品列表
参考文献
[1] Takahashi, K., Yamanaka, S. (2006) Induction ofpluripotent stem cells from mouse embryonic andadult fibroblast cultures by defined factors. Cell,126(4):663-76.
[2] Wernig, M.. Meissner, A., Foreman, R.,
Brambrink, T., Ku, M., Hochedlinger, K. Bernstein,B.E.. Jaenisch, R. (2007) In vitro reprogramming offibroblasts into a pluripotent ES-cell-like state.Nature, 448(7151):318-24.
Antosiewicz- Bourget, J., Frane, J.L., Tian, S., Nie,J., Jonsdottir, G .A., Ruotti, V., Stewart, R., Slukvin,l.l., Thomson, J.A. (2007) Induced pluripotent stem cell lines derived from human somaticcells. Science, 318(5858):1917-20.
[8] Shi, Y., Desponts, C., Do, J.T., Hahm, H.S.,Schöler, H.R., Ding, S. (2008) Induction ofpluripotent stem cells from mouse embryonicfibroblasts by Oct4 and Klf4 with small-moleculecompounds. Cell Stem Cells, 3(5), 568-574.
[9] Huangfu, D., Osafune, K., Maehr, R., Guo, W.,Eijkelenboom, A., Chen, S., Muhlestein, W., Melton,D.A. (2008) Induction of pluripotent stem cells fromprimary human fibroblasts with only Oct4 and Sox2.Nature Biotechnology, 26(11):1269 -75.
[10] Li, W., Ding, S. (2010) Small molecules thatmodulate embryonic stem cell fate and somatic cellreprogramming. Trends Pharmacological Science,31(1):36-45.
[11] Zhou, H., Wu, S., Joo, J.Y., Zhu, S., Han, D.W.,Lin, T., Trauger, S., Bien, G., Yao, S., Zhu, Y., Siuzdak, G., Schöler, H.R., Duan,L., Ding, S. (2009)Generation of induced pluripotent stem cells usingrecombinant proteins. Cell Stem Cell, 4 (5):381-4. [12] Kim, D., Kim, C.H., Moon, J.l., Chung, Y.G.,Chang, M.Y., Han, B.S., Ko, S., Yang, E., Cha, K.Y.,L anza, R., Kim, K.S. (2009). Generation of humaninduced pluripotent stem cells by direct delivery ofreprogramming proteins. Cell Stem Cell, 4:472-476.
[13] Niwa, H., Miyazaki, J.l., Smith, A.G. (2000)Quantitative expression of Oct- -3/4 defines
differentiation, dedifferentiation or self-renewal ofES cells. Nature Genetics, 24:372-376.
◆重编程的发展历程
重编程技术和递送技术近年来迅速发展，现在已经可以采用多种方法递送和表达必要的重编程因子进行直接重编程。这些方法包括整合逆转录和慢病毒载体，dox诱导表达系统和减少或者去除插入到宿主细胞基因组的瞬时或者可割取的方法。最近突破性的技术是在2010年9月干细胞会议上发布的修饰合成mRNAs，可以高效的进行人成纤维细胞的重编程，基因组不会发生改变。该项学术研究加速了其他策略的发展，会有更多的研究成果。
细胞重编程 指南目录
1.什么是细胞重编程
2.细胞重编程概述
3.mRNA重编程
4.病毒重编程
5.产品列表
参考文献
[1] Takahashi, K., Yamanaka, S. (2006) Induction ofpluripotent stem cells from mouse embryonic andadult fibroblast cultures by defined factors. Cell,126(4):663-76.
[2] Wernig, M.. Meissner, A., Foreman, R.,
Brambrink, T., Ku, M., Hochedlinger, K. Bernstein,B.E.. Jaenisch, R. (2007) In vitro reprogramming offibroblasts into a pluripotent ES-cell-like state.Nature, 448(7151):318-24.
[3] Boland, M.J., Hazen, J.L., Nazor, K.L.,
Rodriguez, A.R., Gifford, W., Martin, G., Kupriyanov, S., Balwin, K.K. (2009) Adult mice generated frominduced pluripotent stem cells. Nature, 461(7260):91-4.
[4] Kang, L., Wang, J., Zhang, Y., Kou, Z., Gao, S.(2009) iPS cells can support full-term developmentof tetraploid blastocyst-complemented embryos.Cell Stem Cell 5; 135-138.
[5] Zhao, X.Y., Li, W., Lu, Z., Liu, L., Tong, M., Hai,T., Hao, J., Guo, C.L., Ma, Q.W., Wang, L., Zeng, F.,Zhou, Q. (2009) iPS cells produce viable micethrough tetraploid complementation. Nature 461;86-90
[6] Takhashi, K., Tanabe, K., Ohnuki, M., Narita, M.,lchisaka, T., Tomoda, K., Yamanaka S. (2007)Induction of pluripotent stem cells from adulthuman fibroblasts by defined factors. Cell,131(5):861-72.
[7] Yu, J., Vodyanik, M.A., Smuga-Otto, K.,
Antosiewicz- Bourget, J., Frane, J.L., Tian, S., Nie,J., Jonsdottir, G .A., Ruotti, V., Stewart, R., Slukvin,l.l., Thomson, J.A. (2007) Induced pluripotent stem cell lines derived from human somaticcells. Science, 318(5858):1917-20.
[8] Shi, Y., Desponts, C., Do, J.T., Hahm, H.S.,Schöler, H.R., Ding, S. (2008) Induction ofpluripotent stem cells from mouse embryonicfibroblasts by Oct4 and Klf4 with small-moleculecompounds. Cell Stem Cells, 3(5), 568-574.
[9] Huangfu, D., Osafune, K., Maehr, R., Guo, W.,Eijkelenboom, A., Chen, S., Muhlestein, W., Melton,D.A. (2008) Induction of pluripotent stem cells fromprimary human fibroblasts with only Oct4 and Sox2.Nature Biotechnology, 26(11):1269 -75.
[10] Li, W., Ding, S. (2010) Small molecules thatmodulate embryonic stem cell fate and somatic cellreprogramming. Trends Pharmacological Science,31(1):36-45.
[11] Zhou, H., Wu, S., Joo, J.Y., Zhu, S., Han, D.W.,Lin, T., Trauger, S., Bien, G., Yao, S., Zhu, Y., Siuzdak, G., Schöler, H.R., Duan,L., Ding, S. (2009)Generation of induced pluripotent stem cells usingrecombinant proteins. Cell Stem Cell, 4 (5):381-4. [12] Kim, D., Kim, C.H., Moon, J.l., Chung, Y.G.,Chang, M.Y., Han, B.S., Ko, S., Yang, E., Cha, K.Y.,L anza, R., Kim, K.S. (2009). Generation of humaninduced pluripotent stem cells by direct delivery ofreprogramming proteins. Cell Stem Cell, 4:472-476.
[13] Niwa, H., Miyazaki, J.l., Smith, A.G. (2000)Quantitative expression of Oct- -3/4 defines
differentiation, dedifferentiation or self-renewal ofES cells. Nature Genetics, 24:372-376.
[14] Jia, F., Wilson, K.D., Sun, N., Gupta, D.M.,Huang, M., Li, Z., Panetta, N.J., Chen, Z.Y.,
Robbins, R.C., Kay, M.A., Longaker, M.T., Wu, J.C.(2010) A nonviral minicircle vector for derivinghuman iPS cells. Nature Methods, 7(3):197-9.
[15] Okita, K., Nakagawa, M., Hyenjong, H.,lchisaka, T., Yamanaka, S. (2008) Generation of
mouse induced pluripotent stem cells without viralvectors. Science, 322(5903):949 - 953.
[16] Carey, B.W., Markoulaki, S., Hanna, J., Saha,K., Gao, Q., Mitalipova, M., Jaenisch, R. (2009)Reprogramming of murinand human somatic cellsusing a single polycistronic vector. PNAS,106(1):157-62.
[17] Wernig, M., Lengner, C.J., Hanna, J., Lodato,M.A., Steine, E., Foreman, R., Staerk, J.,Markoulaki, S., Jaenisch, R. (2008) A drug-inducible transgenic system for directreprogramming of multiple somatic cell types.Nature Biotechnology,26(8):916-24.
[18] Hockemeyer, D., Soldner, F., Cook, E.G., Gao,Q., Mitalipova, M., Jaenisch, R. (2008) A drug-inducible system for direct reprogramming of human somatic cells to pluripotency. Cell Stem Cell,3(3):346-53.
[19] Stadtfeld, M., Nagaya, M., Utikal, J., Weir, G.,Hochedlinger, K. (2008) Induced pluripotent stemcells generated without viral integration. Science,322(5903):945-9.
[20] Soldner, F., Hockemeyer, D., Beard, C., Gao,Q., Bell, G.W., Cook, E.G., Hargus, G., Blak, A., Cooper, o., Mitalipova, M.,lsacson,O., Jaenisch, R.(2009) Parkinson' s disease patient- -derived
[21] Zhou, W., Freed., C. (2009) Adenoviral GeneDelivery Can Reprogram Human Fibroblasts toInduced Pluripotent StemCells. Stem Cells27(11):2667 - 2674.
[22] Woltjen, K., Michael, I.P., Mohseni, P., Desai,R., Mileikovsky, M., Hämäläinen, R., Cowling, R.,Wang, W., Liu, P., Gertsenstein,M., Kaji, K., Sung, H.K., Nagy, A. (2009) PiggyBac transposition reprograms fibroblasts to induced pluripotent stemcells. Nature, 458(7239):766-70.
[23] Yu, J., Hu, K., Smuga-Otto, K., Tian, S.,Stewart, R., Slukvin, l.I. Thomson, J.A. (2009) Human induced pluripotent stemcells free of vector and transgene sequences. Science,324(5928):797-801.
[21] Zhou, W., Freed., C. (2009) Adenoviral GeneDelivery Can Reprogram Human Fibroblasts toInduced Pluripotent StemCells. Stem Cells27(11):2667 - 2674.
[22] Woltjen, K., Michael, I.P., Mohseni, P., Desai,R., Mileikovsky, M., Hämäläinen, R., Cowling, R.,Wang, W., Liu, P., Gertsenstein,M., Kaji, K., Sung, H.K., Nagy, A. (2009) PiggyBac transposition reprograms fibroblasts to induced pluripotent stemcells. Nature, 458(7239):766-70.
[23] Yu, J., Hu, K., Smuga-Otto, K., Tian, S.,Stewart, R., Slukvin, l.I. Thomson, J.A. (2009) Human induced pluripotent stemcells free of vector and transgene sequences. Science,324(5928):797-801.
[24] Nakagawa M., Koyanagi M., Tanabe K.,Takahashi K., lchisaka T., Aoi T., Okita K.,Mochiduki Y., Takizawa N.,Y amanaka S. (2008)Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts.Nature Biotechnology, 26(1):101-6.
[25] Warren, L., Manos, P.D., Ahfeldt, T., Loh, Y.H.,Li, H., Lau, F., Ebina, W., Mandal, P.K., Smith, Z.D.,Meissner, A., Daley, D.Q., Brack, A.S., Collins, J.J.,Cowan, c., Schlaeger, T.M., Rossi, D.J. (2010)Highly Efficient Reprogramming to PluripotencyandDirected Differentiation of Human Cells withSynthetic Modified mRNA. Cell Stem Cell. 7:618.
[26] Yakubov, E., Rechavi, G., Rozenblatt, S., Givol,D. (2010) Reprogramming of Human Fibroblasts toPluripotent Stem Cells using mRNA of FourTranscription Factors. Biochem Biophys ResCommun.394:189.
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文献和实验相关实验
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Cell Stem Cell：邓宏魁课题组建立更加快速高效的人体细胞化学重编程体系
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什么是细胞重编程
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