Chemical reprogramming for cell fate manipulation: Methods, applications, and perspectives

Wang, Jinlin; Sun, Shicheng; Deng, Hongkui

doi:10.1016/j.stem.2023.08.001

Cited by 91Pluripotent Stem Cells ResearchDevelopmental Biology and Gene RegulationMesenchymal stem cell research

Chemical reprogramming for cell fate manipulation: Methods, applications, and perspectives

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Wang, Jinlin, Sun, Shicheng, Deng, Hongkui·2023·Cell Stem Cell

DOI 10.1016/j.stem.2023.08.001

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Abstract

Chemical reprogramming offers an unprecedented opportunity to control somatic cell fate and generate desired cell types including pluripotent stem cells for applications in biomedicine in a precise, flexible, and controllable manner. Recent success in the chemical reprogramming of human somatic cells by activating a regeneration-like program provides an alternative way of producing stem cells for clinical translation. Likewise, chemical manipulation enables the capture of multiple (stem) cell states, ranging from totipotency to the stabilization of somatic fates in vitro. Here, we review progress in using chemical approaches for cell fate manipulation in addition to future opportunities in this promising field.

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CiPSCs are generated from somatic cells using abiotic, small-molecule chemicals as reprogramming factors, unlike conventional iPSCs which use genetic overexpression of transcription factors.
“Different from conventional iPSCs, which are generated from somatic cells by genetic overexpression of transcription factors, the generation of CiPSCs from somatic cells employs abiotic, small-molecule chemicals as reprogramming factors”
From Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient. (2024) · cites this paper as [6]
CiPSC generation is easily manufactured and standardized, non-genome integrating, scalable, and fine-tunable.
“the generation of CiPSCs from somatic cells employs abiotic, small-molecule chemicals as reprogramming factors that are easily manufactured and standardized, non-genome integrating, scalable, and fine-tunable.”
From Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient. (2024) · cites this paper as [6]
The small molecules used in the chemical reprogramming approach offer ease of manufacture and standardization and are highly controllable, scalable, and cost-effective, which are important for standardized manufacturing of therapeutic cells.
“The small molecules used in the chemical reprogramming approach offer ease of manufacture and standardization and are highly controllable, scalable, and cost-effective, which are important for standardized manufacturing of therapeutic cells.6”
From Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient. (2024) · cites this paper as [6]

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Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium
Sato, T., Stange, D. E., Ferrante, M., Vries, R. G. J., van Es, J. H., van den Brink, S., van Houdt, W. J., Pronk, A., van Gorp, J., Siersema, P. D., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.07.050 · Cited by 3,753 · see citing works
A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles
Subramanian, A., Narayan, R., Corsello, S. M., Peck, D. D., Natoli, T. E., Lu, X., Gould, J., Davis, J. F., Tubelli, A. A., Asiedu, J. K., et al. (2017) · Cell · doi:10.1016/j.cell.2017.10.049 · Cited by 3,515 · see citing works
The ground state of embryonic stem cell self-renewal
Ying, Q.-L., Wray, J., Nichols, J., Batlle-Morera, L., Doble, B., Woodgett, J., Cohen, P., & Smith, A. (2008) · Nature · doi:10.1038/nature06968 · Cited by 3,442 · see citing works
Highly accurate protein structure prediction for the human proteome
Tunyasuvunakool, K., Adler, J., Wu, Z., Green, T., Zielinski, M., Žídek, A., Bridgland, A., Cowie, A., Meyer, C., Laydon, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03828-1 · Cited by 3,025 · see citing works
Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA
Warren, L., Manos, P. D., Ahfeldt, T., Loh, Y.-H., Li, H., Lau, F., Ebina, W., Mandal, P. K., Smith, Z. D., Meissner, A., et al. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.08.012 · Cited by 2,662 · see citing works
Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver
Huch, M., Gehart, H., van Boxtel, R., Hamer, K., Blokzijl, F., Verstegen, M. M. A., Ellis, E., van Wenum, M., Fuchs, S. A., de Ligt, J., et al. (2015) · Cell · doi:10.1016/j.cell.2014.11.050 · Cited by 1,619 · see citing works
Induced pluripotent stem cell technology: a decade of progress.
Shi, Y., Inoue, H., Wu, J. C., & Yamanaka, S. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.245 · Cited by 1,525 · see citing works
A Molecular Roadmap of Reprogramming Somatic Cells into iPS Cells
Polo, J. M., Anderssen, E., Walsh, R. M., Schwarz, B. A., Nefzger, C. M., Lim, S. M., Borkent, M., Apostolou, E., Alaei, S., Cloutier, J., et al. (2012) · Cell · doi:10.1016/j.cell.2012.11.039 · Cited by 861 · see citing works
Long-Term Expansion of Functional Mouse and Human Hepatocytes as 3D Organoids
Hu, H., Gehart, H., Artegiani, B., LÖpez-Iglesias, C., Dekkers, F., Basak, O., van Es, J., Chuva de Sousa Lopes, S. M., Begthel, H., Korving, J., et al. (2018) · Cell · doi:10.1016/j.cell.2018.11.013 · Cited by 837 · see citing works
Reprogramming to recover youthful epigenetic information and restore vision
Lu, Y., Brommer, B., Tian, X., Krishnan, A., Meer, M., Wang, C., Vera, D. L., Zeng, Q., Yu, D., Bonkowski, M. S., et al. (2020) · Nature · doi:10.1038/s41586-020-2975-4 · Cited by 820 · see citing works
Pioneer Transcription Factors Target Partial DNA Motifs on Nucleosomes to Initiate Reprogramming
Soufi, A., Garcia, M. F., Jaroszewicz, A., Osman, N., Pellegrini, M., & Zaret, K. S. (2015) · Cell · doi:10.1016/j.cell.2015.03.017 · Cited by 780 · see citing works
Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state
Lapasset, L., Milhavet, O., Prieur, A., Besnard, E., Babled, A., Aït-Hamou, N., Leschik, J., Pellestor, F., Ramirez, J.-M., De Vos, J., et al. (2011) · Genes & Development · doi:10.1101/gad.173922.111 · Cited by 570 · see citing works
Cooperative Binding of Transcription Factors Orchestrates Reprogramming
Chronis, C., Fiziev, P., Papp, B., Butz, S., Bonora, G., Sabri, S., Ernst, J., & Plath, K. (2017) · Cell · doi:10.1016/j.cell.2016.12.016 · Cited by 555 · see citing works
Single-cell CUT&Tag profiles histone modifications and transcription factors in complex tissues
Bartosovic, M., Kabbe, M., & Castelo-Branco, G. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-00869-9 · Cited by 483 · see citing works
Bridging the regeneration gap: Genetic insights from diverse animal models
Alvarado, A. S., & Tsonis, P. A. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1923 · Cited by 467 · see citing works
Small-Molecule-Driven Direct Reprogramming of Mouse Fibroblasts into Functional Neurons.
Li, X., Zuo, X., Jing, J., Ma, Y., Wang, J., Liu, D., Zhu, J., Du, X., Xiong, L., Du, Y., et al. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.06.003 · Cited by 428 · see citing works
Self-citation
Chemical reprogramming of human somatic cells to pluripotent stem cells.
Guan, J., Wang, G., Wang, J., Zhang, Z., Fu, Y., Cheng, L., Meng, G., Lyu, Y., Zhu, J., Li, Y., et al. (2022) · Nature · doi:10.1038/s41586-022-04593-5 · Cited by 388 · see citing works
Self-citation
Revisiting astrocyte to neuron conversion with lineage tracing in vivo
Wang, L.-L., Serrano, C., Zhong, X., Ma, S., Zou, Y., & Zhang, C.-L. (2021) · Cell · doi:10.1016/j.cell.2021.09.005 · Cited by 329 · see citing works
Role of H3K9me3 heterochromatin in cell identity establishment and maintenance
Nicetto, D., & Zaret, K. S. (2019) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2019.04.013 · Cited by 312 · see citing works
Transient non-integrative expression of nuclear reprogramming factors promotes multifaceted amelioration of aging in human cells.
Sarkar, T. J., Quarta, M., Mukherjee, S., Colville, A., Paine, P., Doan, L., Tran, C. M., Chu, C. R., Horvath, S., Qi, L. S., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15174-3 · Cited by 308 · see citing works
In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice.
Browder, K. C., Reddy, P., Yamamoto, M., Haghani, A., Guillen, I. G., Sahu, S., Wang, C., Luque, Y., Prieto, J., Shi, L., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00183-2 · Cited by 253 · see citing works
In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity
Zhang, K., Zhang, L., Liu, W., Ma, X., Cen, J., Sun, Z., Wang, C., Feng, S., Zhang, Z., Yue, L., et al. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.10.018 · Cited by 252 · see citing works
Direct reprogramming of mouse fibroblasts into cardiomyocytes with chemical cocktails.
Fu, Y., Huang, C., Xu, X., Gu, H., Ye, Y., Jiang, C., Qiu, Z., & Xie, X. (2015) · Cell Research · doi:10.1038/cr.2015.99 · Cited by 248 · see citing works
Principles of signaling pathway modulation for enhancing human naive pluripotency induction
Bayerl, J., Ayyash, M., Shani, T., Manor, Y. S., Gafni, O., Massarwa, R., Kalma, Y., Aguilera-Castrejon, A., Zerbib, M., Amir, H., et al. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.04.001 · Cited by 165 · see citing works
Establishment of intestinal organoid cultures modeling injury-associated epithelial regeneration
Qu, M., Xiong, L., Lyu, Y., Zhang, X., Shen, J., Guan, J., Chai, P., Lin, Z., Nie, B., Li, C., et al. (2021) · Cell Research · doi:10.1038/s41422-020-00453-x · Cited by 138 · see citing works
Self-citation
Chemically induced reprogramming to reverse cellular aging
Yang, J.-H., Petty, C. A., Dixon-McDougall, T., Lopez, M. V., Tyshkovskiy, A., Maybury-Lewis, S., Tian, X., Ibrahim, N., Chen, Z., Griffin, P. T., et al. (2023) · Aging · doi:10.18632/aging.204896 · Cited by 136 · see citing works
Highly efficient and rapid generation of human pluripotent stem cells by chemical reprogramming.
Liuyang, S., Wang, G., Wang, Y., He, H., Lyu, Y., Cheng, L., Yang, Z., Guan, J., Fu, Y., Zhu, J., et al. (2023) · Cell Stem Cell · doi:10.1016/j.stem.2023.02.008 · Cited by 136 · see citing works
Self-citation
Induction of mouse totipotent stem cells by a defined chemical cocktail.
Hu, Y., Yang, Y., Tan, P., Zhang, Y., Han, M., Yu, J., Zhang, X., Jia, Z., Wang, D., Yao, K., et al. (2023) · Nature · doi:10.1038/s41586-022-04967-9 · Cited by 116 · see citing works
Repressing PTBP1 fails to convert reactive astrocytes to dopaminergic neurons in a 6-hydroxydopamine mouse model of Parkinson's disease
Chen, W., Zheng, Q., Huang, Q., Ma, S., & Li, M. (2022) · eLife · doi:10.7554/elife.75636 · Cited by 89 · see citing works
Implantation underneath the abdominal anterior rectus sheath enables effective and functional engraftment of stem-cell-derived islets
Liang, Z., Sun, D., Lu, S., Lei, Z., Wang, S., Luo, Z., Zhan, J., Wu, S., Jiang, Y., Lu, Z., et al. (2023) · Nature Metabolism · doi:10.1038/s42255-022-00713-7 · Cited by 59 · see citing works
Self-citation

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Research works printed but not linked: 126

[1]1. Jopling, C. ∙ Boue, S. ∙ Izpisua Belmonte, J.C. Dedifferentiation, transdifferentiation and reprogramming: three routes to regeneration Nat. Rev. Mol. Cell Biol. 2011; 12:79-89 Crossref Scopus (485) PubMed Google Scholar
[2]2. Knapp, D. ∙ Tanaka, E.M. Regeneration and reprogramming Curr. Opin. Genet. Dev. 2012; 22:485-493 Crossref Scopus (38) PubMed Google Scholar
[3]3. Sánchez Alvarado, A. ∙ Yamanaka, S. Rethinking differentiation: stem cells, regeneration, and plasticity Cell. 2014; 157:110-119 Full Text Full Text (PDF) Scopus (183) PubMed Google Scholar
[5]5. Birnbaum, K.D. ∙ Sánchez Alvarado, A. Slicing across kingdoms: regeneration in plants and animals Cell. 2008; 132:697-710 Full Text Full Text (PDF) Scopus (293) PubMed Google Scholar
[6]6. Gurdon, J.B. The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles J. Embryol. Exp. Morphol. 1962; 10:622-640 PubMed Google Scholar
[7]7. Campbell, K.H. ∙ McWhir, J. ∙ Ritchie, W.A. ... Sheep cloned by nuclear transfer from a cultured cell line Nature. 1996; 380:64-66 Crossref Scopus (1512) PubMed Google Scholar
[8]8. Wakayama, T. ∙ Perry, A.C. ∙ Zuccotti, M. ... Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei Nature. 1998; 394:369-374 Crossref Scopus (1969) PubMed Google Scholar
[9]9. Takahashi, K. ∙ Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors Cell. 2006; 126:663-676 Full Text Full Text (PDF) Scopus (19737) PubMed Google Scholar
[10]10. Takahashi, K. ∙ Tanabe, K. ∙ Ohnuki, M. ... Induction of pluripotent stem cells from adult human fibroblasts by defined factors Cell. 2007; 131:861-872 Full Text Full Text (PDF) Scopus (15603) PubMed Google Scholar
[11]11. Yu, J. ∙ Vodyanik, M.A. ∙ Smuga-Otto, K. ... Induced pluripotent stem cell lines derived from human somatic cells Science. 2007; 318:1917-1920 Crossref Scopus (8383) PubMed Google Scholar
[12]12. Park, I.H. ∙ Zhao, R. ∙ West, J.A. ... Reprogramming of human somatic cells to pluripotency with defined factors Nature. 2008; 451:141-146 Crossref Scopus (2409) PubMed Google Scholar
[14]14. Rowe, R.G. ∙ Daley, G.Q. Induced pluripotent stem cells in disease modelling and drug discovery Nat. Rev. Genet. 2019; 20:377-388 Crossref Scopus (322) PubMed Google Scholar
[15]15. Yamanaka, S. Pluripotent stem cell-based cell therapy-promise and challenges Cell Stem Cell. 2020; 27:523-531 Full Text Full Text (PDF) Scopus (418) PubMed Google Scholar
[16]16. Spencer, D.M. ∙ Wandless, T.J. ∙ Schreiber, S.L. ... Controlling signal transduction with synthetic ligands Science. 1993; 262:1019-1024 Crossref Scopus (703) PubMed Google Scholar
[17]17. Xu, J. ∙ Du, Y. ∙ Deng, H. Direct lineage reprogramming: strategies, mechanisms, and applications Cell Stem Cell. 2015; 16:119-134 Full Text Full Text (PDF) Scopus (309) PubMed Google Scholar
[18]18. Hou, P. ∙ Li, Y. ∙ Zhang, X. ... Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds Science. 2013; 341:651-654 Crossref Scopus (1042) PubMed Google Scholar
[20]20. Xiang, C. ∙ Du, Y. ∙ Meng, G. ... Long-term functional maintenance of primary human hepatocytes in vitro Science. 2019; 364:399-402 Crossref Scopus (123) PubMed Google Scholar
[23]23. Boitano, A.E. ∙ Wang, J. ∙ Romeo, R. ... Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells Science. 2010; 329:1345-1348 Crossref Scopus (805) PubMed Google Scholar
[24]24. Fares, I. ∙ Chagraoui, J. ∙ Gareau, Y. ... Cord blood expansion. Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal Science. 2014; 345:1509-1512 Crossref Scopus (403) PubMed Google Scholar
[25]25. Xiao, X. ∙ Lai, W. ∙ Xie, H. ... Targeting JNK pathway promotes human hematopoietic stem cell expansion Cell Discov. 2019; 5, 2 Crossref Scopus (19) Google Scholar
[26]26. Sakurai, M. ∙ Ishitsuka, K. ∙ Ito, R. ... Chemically defined cytokine-free expansion of human haematopoietic stem cells Nature. 2023; 615:127-133 Crossref Scopus (16) PubMed Google Scholar
[28]28. Gafni, O. ∙ Weinberger, L. ∙ Mansour, A.A. ... Derivation of novel human ground state naive pluripotent stem cells Nature. 2013; 504:282-286 Crossref Scopus (797) PubMed Google Scholar
[29]29. Takashima, Y. ∙ Guo, G. ∙ Loos, R. ... Resetting transcription factor control circuitry toward ground-state pluripotency in human Cell. 2014; 158:1254-1269 Full Text Full Text (PDF) Scopus (644) PubMed Google Scholar
[30]30. Theunissen, T.W. ∙ Powell, B.E. ∙ Wang, H. ... Systematic identification of culture conditions for induction and maintenance of naive human pluripotency Cell Stem Cell. 2014; 15:471-487 Full Text Full Text (PDF) Scopus (575) PubMed Google Scholar
[31]31. Guo, G. ∙ von Meyenn, F. ∙ Rostovskaya, M. ... Epigenetic resetting of human pluripotency Development. 2017; 144:2748-2763 Crossref Scopus (173) PubMed Google Scholar
[33]33. Yang, Y. ∙ Liu, B. ∙ Xu, J. ... Derivation of pluripotent stem cells with in vivo embryonic and extraembryonic potency Cell. 2017; 169:243-257.e25 Full Text Full Text (PDF) Scopus (309) PubMed Google Scholar
[34]34. Yang, J. ∙ Ryan, D.J. ∙ Wang, W. ... Establishment of mouse expanded potential stem cells Nature. 2017; 550:393-397 Crossref Scopus (173) PubMed Google Scholar
[35]35. Gao, X. ∙ Nowak-Imialek, M. ∙ Chen, X. ... Establishment of porcine and human expanded potential stem cells Nat. Cell Biol. 2019; 21:687-699 Crossref Scopus (202) PubMed Google Scholar
[36]36. Shen, H. ∙ Yang, M. ∙ Li, S. ... Mouse totipotent stem cells captured and maintained through spliceosomal repression Cell. 2021; 184:2843-2859.e20 Full Text Full Text (PDF) Scopus (68) PubMed Google Scholar
[37]37. Xu, Y. ∙ Zhao, J. ∙ Ren, Y. ... Derivation of totipotent-like stem cells with blastocyst-like structure forming potential Cell Res. 2022; 32:513-529 Crossref Scopus (28) PubMed Google Scholar
[38]38. Yang, M. ∙ Yu, H. ∙ Yu, X. ... Chemical-induced chromatin remodeling reprograms mouse ESCs to totipotent-like stem cells Cell Stem Cell. 2022; 29:400-418.e13 Full Text Full Text (PDF) Scopus (32) PubMed Google Scholar
[40]40. Mazid, M.A. ∙ Ward, C. ∙ Luo, Z. ... Rolling back human pluripotent stem cells to an eight-cell embryo-like stage Nature. 2022; 605:315-324 Crossref Scopus (42) PubMed Google Scholar
[41]41. Yu, X. ∙ Liang, S. ∙ Chen, M. ... Recapitulating early human development with 8C-like cells Cell Rep. 2022; 39, 110994 Full Text Full Text (PDF) Scopus (12) Google Scholar
[43]43. Hu, W. ∙ Qiu, B. ∙ Guan, W. ... Direct conversion of normal and Alzheimer's disease human fibroblasts into neuronal cells by small molecules Cell Stem Cell. 2015; 17:204-212 Full Text Full Text (PDF) Scopus (362) PubMed Google Scholar
[44]44. Cheng, L. ∙ Hu, W. ∙ Qiu, B. ... Generation of neural progenitor cells by chemical cocktails and hypoxia Cell Res. 2014; 24:665-679 Crossref Scopus (178) PubMed Google Scholar
[45]45. Zhang, M. ∙ Lin, Y.H. ∙ Sun, Y.J. ... Pharmacological reprogramming of fibroblasts into neural stem cells by signaling-directed transcriptional activation Cell Stem Cell. 2016; 18:653-667 Full Text Full Text (PDF) Scopus (143) PubMed Google Scholar
[47]47. Cao, N. ∙ Huang, Y. ∙ Zheng, J. ... Conversion of human fibroblasts into functional cardiomyocytes by small molecules Science. 2016; 352:1216-1220 Crossref Scopus (267) PubMed Google Scholar
[48]48. Bai, Y. ∙ Yang, Z. ∙ Xu, X. ... Direct chemical induction of hepatocyte-like cells with capacity for liver repopulation Hepatology. 2023; 77:1550-1565 Crossref Scopus (7) PubMed Google Scholar
[49]49. Zhang, L. ∙ Yin, J.C. ∙ Yeh, H. ... Small molecules efficiently reprogram human astroglial cells into functional neurons Cell Stem Cell. 2015; 17:735-747 Full Text Full Text (PDF) Scopus (212) PubMed Google Scholar
[50]50. Yin, J.C. ∙ Zhang, L. ∙ Ma, N.X. ... Chemical conversion of human fetal astrocytes into neurons through modulation of multiple signaling pathways Stem Cell Rep. 2019; 12:488-501 Full Text Full Text (PDF) Scopus (59) PubMed Google Scholar
[51]51. Ma, Y. ∙ Xie, H. ∙ Du, X. ... In vivo chemical reprogramming of astrocytes into neurons Cell Discov. 2021; 7, 12 Crossref Scopus (33) Google Scholar
[52]52. Huang, C. ∙ Tu, W. ∙ Fu, Y. ... Chemical-induced cardiac reprogramming in vivo Cell Res. 2018; 28:686-689 Crossref Scopus (44) PubMed Google Scholar
[53]53. Huangfu, D. ∙ Maehr, R. ∙ Guo, W. ... Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds Nat. Biotechnol. 2008; 26:795-797 Crossref Scopus (1347) PubMed Google Scholar
[54]54. Huangfu, D. ∙ Osafune, K. ∙ Maehr, R. ... Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2 Nat. Biotechnol. 2008; 26:1269-1275 Crossref Scopus (1138) PubMed Google Scholar
[55]55. Li, W. ∙ Li, K. ∙ Wei, W. ... Chemical approaches to stem cell biology and therapeutics Cell Stem Cell. 2013; 13:270-283 Full Text Full Text (PDF) Scopus (137) PubMed Google Scholar
[56]56. Theunissen, T.W. ∙ Jaenisch, R. Molecular control of induced pluripotency Cell Stem Cell. 2014; 14:720-734 Full Text Full Text (PDF) Scopus (102) PubMed Google Scholar
[57]57. Li, Y. ∙ Zhang, Q. ∙ Yin, X. ... Generation of iPSCs from mouse fibroblasts with a single gene, Oct4, and small molecules Cell Res. 2011; 21:196-204 Crossref Scopus (274) PubMed Google Scholar
[58]58. Chen, J. ∙ Liu, J. ∙ Yang, J. ... BMPs functionally replace Klf4 and support efficient reprogramming of mouse fibroblasts by Oct4 alone Cell Res. 2011; 21:205-212 Crossref Scopus (108) PubMed Google Scholar
[59]59. Zhu, S. ∙ Li, W. ∙ Zhou, H. ... Reprogramming of human primary somatic cells by OCT4 and chemical compounds Cell Stem Cell. 2010; 7:651-655 Full Text Full Text (PDF) Scopus (551) PubMed Google Scholar
[60]60. Mahato, B. ∙ Kaya, K.D. ∙ Fan, Y. ... Pharmacologic fibroblast reprogramming into photoreceptors restores vision Nature. 2020; 581:83-88 Crossref Scopus (57) PubMed Google Scholar
[61]61. Schöler, H.R. ∙ Hatzopoulos, A.K. ∙ Balling, R. ... A family of octamer-specific proteins present during mouse embryogenesis: evidence for germline-specific expression of an Oct factor EMBO J. 1989; 8:2543-2550 Crossref Scopus (515) PubMed Google Scholar
[62]62. Nichols, J. ∙ Zevnik, B. ∙ Anastassiadis, K. ... Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4 Cell. 1998; 95:379-391 Full Text Full Text (PDF) Scopus (0) PubMed Google Scholar
[63]63. Niwa, H. ∙ Miyazaki, J. ∙ Smith, A.G. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells Nat. Genet. 2000; 24:372-376 Crossref Scopus (2947) PubMed Google Scholar
[64]64. Feldman, N. ∙ Gerson, A. ∙ Fang, J. ... G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis Nat. Cell Biol. 2006; 8:188-194 Crossref Scopus (530) PubMed Google Scholar
[65]65. Epsztejn-Litman, S. ∙ Feldman, N. ∙ Abu-Remaileh, M. ... De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes Nat. Struct. Mol. Biol. 2008; 15:1176-1183 Crossref Scopus (355) PubMed Google Scholar
[67]67. Radzisheuskaya, A. ∙ Silva, J.C. Do all roads lead to Oct4? the emerging concepts of induced pluripotency Trends Cell Biol. 2014; 24:275-284 Full Text Full Text (PDF) Scopus (78) PubMed Google Scholar
[69]69. Zhao, Y. ∙ Zhao, T. ∙ Guan, J. ... A XEN-like state bridges somatic cells to pluripotency during chemical reprogramming Cell. 2015; 163:1678-1691 Full Text Full Text (PDF) Scopus (177) PubMed Google Scholar
[70]70. Ye, J. ∙ Ge, J. ∙ Zhang, X. ... Pluripotent stem cells induced from mouse neural stem cells and small intestinal epithelial cells by small molecule compounds Cell Res. 2016; 26:34-45 Crossref Scopus (55) PubMed Google Scholar
[71]71. Cao, S. ∙ Yu, S. ∙ Li, D. ... Chromatin accessibility dynamics during chemical induction of pluripotency Cell Stem Cell. 2018; 22:529-542.e5 Full Text Full Text (PDF) Scopus (62) PubMed Google Scholar
[72]72. Chen, Y. ∙ Lu, J. ∙ Xu, Y. ... The chemical reprogramming of unipotent adult germ cells towards authentic pluripotency and de novo establishment of imprinting Protein Cell. 2023; 14:477-496 Crossref Scopus (1) PubMed Google Scholar
[74]74. Long, Y. ∙ Wang, M. ∙ Gu, H. ... Bromodeoxyuridine promotes full-chemical induction of mouse pluripotent stem cells Cell Res. 2015; 25:1171-1174 Crossref Scopus (51) PubMed Google Scholar
[75]75. Wang, W. ∙ Ren, S. ∙ Lu, Y. ... Inhibition of Syk promotes chemical reprogramming of fibroblasts via metabolic rewiring and H(2) S production EMBO J. 2021; 40, e106771 Crossref Scopus (10) Google Scholar
[76]76. Jin, Y. ∙ Lu, Y. ∙ Lin, L. ... Harnessing endogenous transcription factors directly by small molecules for chemically induced pluripotency inception Proc. Natl. Acad. Sci. USA. 2023; 120, e2215155120 Crossref Scopus (2) Google Scholar
[77]77. Tian, C. ∙ Liu, L. ∙ Ye, X. ... Functional oocytes derived from granulosa cells Cell Rep. 2019; 29:4256-4267.e9 Full Text Full Text (PDF) Scopus (28) PubMed Google Scholar
[78]78. Tachibana, M. ∙ Amato, P. ∙ Sparman, M. ... Human embryonic stem cells derived by somatic cell nuclear transfer Cell. 2013; 153:1228-1238 Full Text Full Text (PDF) Scopus (567) PubMed Google Scholar
[79]79. Barrero, M.J. ∙ Boué, S. ∙ Izpisúa Belmonte, J.C. Epigenetic mechanisms that regulate cell identity Cell Stem Cell. 2010; 7:565-570 Full Text Full Text (PDF) Scopus (80) PubMed Google Scholar
[80]80. Hawkins, R.D. ∙ Hon, G.C. ∙ Lee, L.K. ... Distinct epigenomic landscapes of pluripotent and lineage-committed human cells Cell Stem Cell. 2010; 6:479-491 Full Text Full Text (PDF) Scopus (633) PubMed Google Scholar
[82]82. Goldman, J.A. ∙ Poss, K.D. Gene regulatory programmes of tissue regeneration Nat. Rev. Genet. 2020; 21:511-525 Crossref Scopus (70) PubMed Google Scholar
[83]83. Ludwig, T.E. ∙ Levenstein, M.E. ∙ Jones, J.M. ... Derivation of human embryonic stem cells in defined conditions Nat. Biotechnol. 2006; 24:185-187 Crossref Scopus (921) PubMed Google Scholar
[84]84. Cahan, P. ∙ Daley, G.Q. Origins and implications of pluripotent stem cell variability and heterogeneity Nat. Rev. Mol. Cell Biol. 2013; 14:357-368 Crossref Scopus (243) PubMed Google Scholar
[85]85. Du, Y. ∙ Liang, Z. ∙ Wang, S. ... Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates Nat. Med. 2022; 28:272-282 Crossref Scopus (36) PubMed Google Scholar
[87]87. Ping, W. ∙ Hu, J. ∙ Hu, G. ... Genome-wide DNA methylation analysis reveals that mouse chemical iPSCs have closer epigenetic features to mESCs than OSKM-integrated iPSCs Cell Death Dis. 2018; 9, 187 Crossref Scopus (10) Google Scholar
[88]88. Zhang, M. ∙ Wang, L. ∙ An, K. ... Lower genomic stability of induced pluripotent stem cells reflects increased non-homologous end joining Cancer Commun. 2018; 38, 49 Crossref Scopus (17) Google Scholar
[89]89. Li, Z. ∙ Lu, H. ∙ Yang, W. ... Mouse SCNT ESCs have lower somatic mutation load than syngeneic iPSCs Stem Cell Rep. 2014; 2:399-405 Full Text Full Text (PDF) Scopus (19) PubMed Google Scholar
[91]91. Yu, J. ∙ Hu, K. ∙ Smuga-Otto, K. ... Human induced pluripotent stem cells free of vector and transgene sequences Science. 2009; 324:797-801 Crossref Scopus (1840) PubMed Google Scholar
[92]92. Okita, K. ∙ Matsumura, Y. ∙ Sato, Y. ... A more efficient method to generate integration-free human iPS cells Nat. Methods. 2011; 8:409-412 Crossref Scopus (1442) PubMed Google Scholar
[95]95. Zhao, T. ∙ Fu, Y. ∙ Zhu, J. ... Single-cell RNA-seq reveals dynamic early embryonic-like programs during chemical reprogramming Cell Stem Cell. 2018; 23:31-45.e7 Full Text Full Text (PDF) Scopus (95) PubMed Google Scholar
[96]96. Takahashi, K. ∙ Tanabe, K. ∙ Ohnuki, M. ... Induction of pluripotency in human somatic cells via a transient state resembling primitive streak-like mesendoderm Nat. Commun. 2014; 5, 3678 Crossref Scopus (105) Google Scholar
[97]97. Xenopoulos, P. ∙ Kang, M. ∙ Puliafito, A. ... Heterogeneities in Nanog expression drive stable commitment to pluripotency in the mouse blastocyst Cell Rep. 2015; 10:1508-1520 Full Text Full Text (PDF) Scopus (85) PubMed Google Scholar
[98]98. Jeong, D. ∙ Lee, Y. ∙ Lee, S.W. ... Homogeneity of XEN cells is critical for generation of chemically induced pluripotent stem cells Mol. Cells. 2023; 46:209-218 Crossref Scopus (1) PubMed Google Scholar
[99]99. Parenti, A. ∙ Halbisen, M.A. ∙ Wang, K. ... OSKM induce extraembryonic endoderm stem cells in parallel to induced pluripotent stem cells Stem Cell Rep. 2016; 6:447-455 Full Text Full Text (PDF) Scopus (39) PubMed Google Scholar
[100]100. Guo, L. ∙ Lin, L. ∙ Wang, X. ... Resolving cell fate decisions during somatic cell reprogramming by single-cell RNA-seq Mol. Cell. 2019; 73:815-829.e7 Full Text Full Text (PDF) Scopus (51) PubMed Google Scholar
[101]101. Schiebinger, G. ∙ Shu, J. ∙ Tabaka, M. ... Optimal-transport analysis of single-cell gene expression identifies developmental trajectories in reprogramming Cell. 2019; 176:928-943.e22 Full Text Full Text (PDF) Scopus (266) PubMed Google Scholar
[102]102. Wang, G. ∙ Wang, Y. ∙ Lyu, Y. ... Chemical-induced epigenome resetting for regeneration program activation in human cells Cell Rep. 2023; 42, 112547 Full Text Full Text (PDF) Scopus (1) Google Scholar
[103]103. Fu, H. ∙ Tian, C.L. ∙ Ye, X. ... Dynamics of telomere rejuvenation during chemical induction to pluripotent stem cells Stem Cell Rep. 2018; 11:70-87 Full Text Full Text (PDF) Scopus (37) PubMed Google Scholar
[104]104. Yang, L. ∙ Liu, X. ∙ Song, L. ... Transient Dux expression facilitates nuclear transfer and induced pluripotent stem cell reprogramming EMBO Rep. 2020; 21, e50054 Crossref Scopus (26) Google Scholar
[105]105. Folmes, C.D. ∙ Nelson, T.J. ∙ Martinez-Fernandez, A. ... Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming Cell Metab. 2011; 14:264-271 Full Text Full Text (PDF) Scopus (766) PubMed Google Scholar
[106]106. Panopoulos, A.D. ∙ Yanes, O. ∙ Ruiz, S. ... The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming Cell Res. 2012; 22:168-177 Crossref Scopus (403) PubMed Google Scholar
[108]108. Lin, T.Y. ∙ Gerber, T. ∙ Taniguchi-Sugiura, Y. ... Fibroblast dedifferentiation as a determinant of successful regeneration Dev. Cell. 2021; 56:1541-1551.e6 Full Text Full Text (PDF) Scopus (37) PubMed Google Scholar
[109]109. Neganova, I. ∙ Shmeleva, E. ∙ Munkley, J. ... JNK/SAPK signaling is essential for efficient reprogramming of human fibroblasts to induced pluripotent stem cells Stem Cells. 2016; 34:1198-1212 Crossref Scopus (18) PubMed Google Scholar
[110]110. Li, J. ∙ Bai, Y. ∙ Liu, Y. ... Transcriptome-based chemical screens identify CDK8 as a common barrier in multiple cell reprogramming systems Cell Rep. 2023; 42:112566 Full Text Full Text (PDF) Scopus (1) PubMed Google Scholar
[111]111. Xie, M. ∙ Tang, S. ∙ Li, K. ... Pharmacological reprogramming of somatic cells for regenerative medicine Acc. Chem. Res. 2017; 50:1202-1211 Crossref Scopus (15) PubMed Google Scholar
[112]112. Li, X. ∙ Xu, J. ∙ Deng, H. Small molecule-induced cellular fate reprogramming: promising road leading to Rome Curr. Opin. Genet. Dev. 2018; 52:29-35 Crossref Scopus (28) PubMed Google Scholar
[113]113. Wang, J. ∙ Gu, S. ∙ Liu, F. ... Reprogramming of fibroblasts into expandable cardiovascular progenitor cells via small molecules in xeno-free conditions Nat. Biomed. Eng. 2022; 6:403-420 Crossref Scopus (9) PubMed Google Scholar
[114]114. Wang, Y. ∙ Qin, J. ∙ Wang, S. ... Conversion of human gastric epithelial cells to multipotent endodermal progenitors using defined small molecules Cell Stem Cell. 2016; 19:449-461 Full Text Full Text (PDF) Scopus (62) PubMed Google Scholar
[115]115. Cao, S. ∙ Yu, S. ∙ Chen, Y. ... Chemical reprogramming of mouse embryonic and adult fibroblast into endoderm lineage J. Biol. Chem. 2017; 292:19122-19132 Full Text Full Text (PDF) Scopus (19) PubMed Google Scholar
[118]118. Paksa, A. ∙ Rajagopal, J. The epigenetic basis of cellular plasticity Curr. Opin. Cell Biol. 2017; 49:116-122 Crossref Scopus (35) PubMed Google Scholar
[119]119. Li, X. ∙ Liu, D. ∙ Ma, Y. ... Direct reprogramming of fibroblasts via a chemically induced XEN-like state Cell Stem Cell. 2017; 21:264-273.e7 e267 Full Text Full Text (PDF) Scopus (69) PubMed Google Scholar
[120]120. Han, M. ∙ Yang, X. ∙ Farrington, J.E. ... Digit regeneration is regulated by Msx1 and BMP4 in fetal mice Development. 2003; 130:5123-5132 Crossref Scopus (183) PubMed Google Scholar
[121]121. Neff, A.W. ∙ King, M.W. ∙ Mescher, A.L. Dedifferentiation and the role of sall4 in reprogramming and patterning during amphibian limb regeneration Dev. Dyn. 2011; 240:979-989 Crossref Scopus (39) PubMed Google Scholar
[122]122. Xu, B. ∙ Wellik, D.M. Axial Hox9 activity establishes the posterior field in the developing forelimb Proc. Natl. Acad. Sci. USA. 2011; 108:4888-4891 Crossref Scopus (78) PubMed Google Scholar
[123]123. Shyh-Chang, N. ∙ Zhu, H. ∙ Yvanka de Soysa, T. ... Lin28 enhances tissue repair by reprogramming cellular metabolism Cell. 2013; 155:778-792 Full Text Full Text (PDF) Scopus (266) PubMed Google Scholar
[124]124. Akiyama, R. ∙ Kawakami, H. ∙ Wong, J. ... Sall4-Gli3 system in early limb progenitors is essential for the development of limb skeletal elements Proc. Natl. Acad. Sci. USA. 2015; 112:5075-5080 Crossref Scopus (42) PubMed Google Scholar
[125]125. Taghiyar, L. ∙ Hesaraki, M. ∙ Sayahpour, F.A. ... Msh homeobox 1 (Msx1)- and Msx2-overexpressing bone marrow-derived mesenchymal stem cells resemble blastema cells and enhance regeneration in mice J. Biol. Chem. 2017; 292:10520-10533 Full Text Full Text (PDF) Scopus (18) PubMed Google Scholar
[126]126. Macfarlan, T.S. ∙ Gifford, W.D. ∙ Driscoll, S. ... Embryonic stem cell potency fluctuates with endogenous retrovirus activity Nature. 2012; 487:57-63 Crossref Scopus (727) PubMed Google Scholar
[127]127. Baker, C.L. ∙ Pera, M.F. Capturing totipotent stem cells Cell Stem Cell. 2018; 22:25-34 Full Text Full Text (PDF) Scopus (64) PubMed Google Scholar
[128]128. Posfai, E. ∙ Schell, J.P. ∙ Janiszewski, A. ... Evaluating totipotency using criteria of increasing stringency Nat. Cell Biol. 2021; 23:49-60 Crossref Scopus (81) PubMed Google Scholar
[129]129. Chen, G. ∙ Gulbranson, D.R. ∙ Hou, Z. ... Chemically defined conditions for human iPSC derivation and culture Nat. Methods. 2011; 8:424-429 Crossref Scopus (1011) PubMed Google Scholar
[130]130. March, S. ∙ Ramanan, V. ∙ Trehan, K. ... Micropatterned coculture of primary human hepatocytes and supportive cells for the study of hepatotropic pathogens Nat. Protoc. 2015; 10:2027-2053 Crossref Scopus (104) PubMed Google Scholar
[132]132. Fu, G.B. ∙ Huang, W.J. ∙ Zeng, M. ... Expansion and differentiation of human hepatocyte-derived liver progenitor-like cells and their use for the study of hepatotropic pathogens Cell Res. 2019; 29:8-22 Crossref Scopus (94) PubMed Google Scholar
[133]133. Sato, T. ∙ Vries, R.G. ∙ Snippert, H.J. ... Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche Nature. 2009; 459:262-265 Crossref Scopus (4475) PubMed Google Scholar
[134]134. Yin, X. ∙ Farin, H.F. ∙ van Es, J.H. ... Niche-independent high-purity cultures of Lgr5+ intestinal stem cells and their progeny Nat. Methods. 2014; 11:106-112 Crossref Scopus (374) PubMed Google Scholar
[136]136. Lukonin, I. ∙ Serra, D. ∙ Challet Meylan, L. ... Phenotypic landscape of intestinal organoid regeneration Nature. 2020; 586:275-280 Crossref Scopus (127) PubMed Google Scholar
[139]139. Jung, P. ∙ Sato, T. ∙ Merlos-Suárez, A. ... Isolation and in vitro expansion of human colonic stem cells Nat. Med. 2011; 17:1225-1227 Crossref Scopus (525) PubMed Google Scholar
[140]140. Fujii, M. ∙ Sato, T. Somatic cell-derived organoids as prototypes of human epithelial tissues and diseases Nat. Mater. 2021; 20:156-169 Crossref Scopus (81) PubMed Google Scholar
[141]141. Wagner, Jr., J.E. ∙ Brunstein, C.G. ∙ Boitano, A.E. ... Phase I/II trial of StemRegenin-1 expanded umbilical cord blood hematopoietic stem cells supports testing as a stand-alone graft Cell Stem Cell. 2016; 18:144-155 Full Text Full Text (PDF) Scopus (247) PubMed Google Scholar
[142]142. Cohen, S. ∙ Roy, J. ∙ Lachance, S. ... Hematopoietic stem cell transplantation using single UM171-expanded cord blood: a single-arm, phase 1–2 safety and feasibility study Lancet Haematol. 2020; 7:e134-e145 Full Text Full Text (PDF) Scopus (114) PubMed Google Scholar
[143]143. Singh, P.B. ∙ Zacouto, F. Nuclear reprogramming and epigenetic rejuvenation J. Biosci. 2010; 35:315-319 Crossref Scopus (14) PubMed Google Scholar
[145]145. Ocampo, A. ∙ Reddy, P. ∙ Martinez-Redondo, P. ... In vivo amelioration of age-associated hallmarks by partial reprogramming Cell. 2016; 167:1719-1733.e12 Full Text Full Text (PDF) Scopus (446) PubMed Google Scholar
[147]147. Chondronasiou, D. ∙ Gill, D. ∙ Mosteiro, L. ... Multi-omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming Aging Cell. 2022; 21, e13578 Crossref Scopus (25) PubMed Google Scholar
[149]149. Abad, M. ∙ Mosteiro, L. ∙ Pantoja, C. ... Reprogramming in vivo produces teratomas and iPS cells with totipotency features Nature. 2013; 502:340-345 Crossref Scopus (343) PubMed Google Scholar
[156]156. Napolitano, F. ∙ Rapakoulia, T. ∙ Annunziata, P. ... Automatic identification of small molecules that promote cell conversion and reprogramming Stem Cell Rep. 2021; 16:1381-1390 Full Text Full Text (PDF) Scopus (7) PubMed Google Scholar
[157]157. Zheng, M. ∙ Xie, B. ∙ Okawa, S. ... A single cell-based computational platform to identify chemical compounds targeting desired sets of transcription factors for cellular conversion Stem Cell Rep. 2023; 18:131-144 Full Text Full Text (PDF) Scopus (1) PubMed Google Scholar
[158]158. Mulqueen, R.M. ∙ Pokholok, D. ∙ Norberg, S.J. ... Highly scalable generation of DNA methylation profiles in single cells Nat. Biotechnol. 2018; 36:428-431 Crossref Scopus (141) PubMed Google Scholar
[160]160. Cahan, P. ∙ Cacchiarelli, D. ∙ Dunn, S.J. ... Computational stem cell biology: open questions and guiding principles Cell Stem Cell. 2021; 28:20-32 Full Text Full Text (PDF) Scopus (11) PubMed Google Scholar
[161]161. Ma, T. ∙ Tian, X. ∙ Zhang, B. ... Low-dose metformin targets the lysosomal AMPK pathway through PEN2 Nature. 2022; 603:159-165 Crossref Scopus (129) PubMed Google Scholar

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“Chemical reprogramming o ﬀ ers a unique opportunity to control the fate of somatic cells and generate the desired cell types, including pluripotent stem cells for potential medical applications [11].”
Background
Engineering fibroblast with reprogramming and spheronization for bone defect repair
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“…molecules through static endpoint assays based on cell phenotypes and functions, rather than mimicking natural development by leveraging modular combinations of the dynamic behaviors of small molecules to regulate lineage-specific and differentiation-stage-specific gene expression pattern [11].”
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“Canonical signal transduction proteins, such as Wnt, SHH, MAPK, and epigenetic regulators like DNA methyltransferases and histone deacetylases, can be directly regulated by small molecules (Wang et al., 2023).”
BackgroundInfluential
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“[59] Since the Wnt genes were first identified by Roel Nusse ’ s team in 1982, Wnt signaling has been shown to regulate a wide range of biological processes.”
Hypo-osmolarity promotes naive pluripotency by reshaping cytoskeleton and increasing chromatin accessibility
Lu, R.-H., Lin, B., Lin, Z., Xiong, H., Liu, J., Li, L., Gong, Z., Wang, S., Zhang, M., Ding, J., et al. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.11.037 · Cited by 4 · see citing works
“Since the discovery of iPSCs, numerous strategies have been applied to change cell fate, from transcription factors to small molecules or by physically manipulating extracellular environment [10,59].”
A layered approach to secure the safety and therapeutic efficacy of hiPSC-derived functionalized neuronal tissueoid for repair after complete spinal cord lnjury in rats
Wei, Q., Xing, Q.-Y., Ma, Y.-H., Zhang, K., Ma, W.-S., Zhang, M.-L., Shi, H.-J., Peng, L., Wang, J.-H., Hu, Q.-X., et al. (2026) · Chemical Engineering Journal · doi:10.1016/j.cej.2026.177575 · Cited by 3 · see citing works
Self-citation
A small molecule strategy with forskolin and p38 inhibitor for serum-free muscle stem cell expansion
Lu, H., Liu, Z., Liu, X., Pan, Y., Yan, D., Cheng, X., Zhang, L.-F., Ding, S.-J., Li, C.-B., Zhou, G., et al. (2026) · npj Science of Food · doi:10.1038/s41538-026-00732-8 · Cited by 3 · see citing works
“Among these approaches, small-molecule compounds stand out for their favorable cost-effectiveness, chemical stability, and batch-to-batch consistency 14,54 .”
Efficient chemical reprogramming of human T cells to pluripotent stem cells
Wang, Y.-L., Peng, F., Cheng, R.-Q., Zeng, J., Zeng, W., Mao, J., Fu, X., Chen, G.-X., Liu, T., Yang, Z., et al. (2026) · Cell Research · doi:10.1038/s41422-025-01216-2 · Cited by 3 · see citing works
Self-citation
Molecular basis of cell fate plasticity – insights from the privileged cells
Scalf, S. M., Wu, Q., & Guo, S.-Q. (2025) · Current Opinion in Genetics and Development · doi:10.1016/j.gde.2025.102354 · Cited by 3 · see citing works
Pluripotent Stem Cells: Recent Advances and Emerging Trends
Wang, A. Y. L., Aviña, A. E., Liu, Y., & Kao, H. (2025) · Biomedicines · doi:10.3390/biomedicines13040765 · Cited by 7 · see citing works
“Researchers investigated reprogramming using chemical substances instead of classical transcription factors because these substitutes reduce mutation risks and enhance the process efficiency [22,23].”
Efficient Fabrication of Human Corneal Stromal Cell Spheroids and Promoting Cell Stemness Based on 3D-Printed Derived PDMS Microwell Platform
Chen, Y., Gu, J.-N., Cui, Z.-K., Sun, X.-H., Liang, Y.-Q., Duan, C., Li, X., Su, Z., Zhang, B., Chen, J.-S., et al. (2025) · Biomolecules · doi:10.3390/biom15030438 · Cited by 3
“In contrast, non-genetic and exogenous factors, such as small chemical molecules, conditioned media, or physical methods, are simpler, easier, flexible, ideal, and safer ways to manipulate cell fate [71].”
Distinctive small molecules blend: Promotes lacrimal gland epithelial cell proliferation in vitro and accelerates lacrimal gland injury repair in vivo.
Zeng, B., Xu, L., Wang, G., Shi, R., Wang, K.-R., Wang, S., & Li, C. (2024) · The ocular surface · doi:10.1016/j.jtos.2024.08.014 · Cited by 3 · see citing works
RetSat stabilizes mitotic chromosome segregation in pluripotent stem cells
Cai, W.-Z., Yao, X., Liu, G., Liu, X., Zhao, B., & Shi, P. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05413-x · Cited by 3 · see citing works
“Bo Zhao zhaobo@mail.kiz.ac.cn Peng Shi ship@mail.kiz.ac.cn current developmental biology research and investigations into the mechanisms of developmental diseases broadly [3, 4].”
Background
Tissue engineering RPE sheet derived from hiPSC-RPE cell spheroids supplemented with Y-27632 and RepSox
Wang, W., Yang, T., Chen, S., Liang, L., Wang, Y., Ding, Y., Xiong, W., Ye, X., Guo, Y., Shen, S., et al. (2024) · Journal of Biological Engineering · doi:10.1186/s13036-024-00405-8 · Cited by 3 · see citing works
“Repsox, also known as 616452, functions as an inhibitor of the transforming growth factor-beta (TGF-β) receptor and is widely used in iPSC reprogramming and lineage reprogramming due to its ability to replace Sox2 and c-Myc by inhibiting TGF-β signaling pathways [15, 16].”
Background
Chemical reprogramming regulates Tip60 expression to improve cleavage rates in somatic cell nuclear transfer reconstituted embryos of cashmere goats
Zhe, X.-S., Zhang, L., Ding, R., Ma, H.-R., Zhang, Y., Hao, F., Liu, D.-J., & Li, Y. (2025) · Frontiers in Veterinary Science · doi:10.3389/fvets.2025.1720533 · Cited by 2 · see citing works
Robust generation of clinically applicable human pluripotent stem cells from peripheral blood by chemical reprogramming
Fu, X., Peng, F., Cai, R.-Y., Mao, J., Liu, T., Dong, Y., Cheng, R.-Q., Yang, Z., Chen, G.-X., Li, C., et al. (2025) · Cell Discovery · doi:10.1038/s41421-025-00852-7 · Cited by 2 · see citing works
Self-citation
Reprogramming of human urine cells into cardiomyocytes via a small molecule cocktail in xeno-free conditions
Chen, Y., Li, A., Liu, A.-J., Zheng, W., Fan, H. C., Zhang, J., & Huang, C. (2025) · Communications Medicine · doi:10.1038/s43856-025-00963-y · Cited by 2 · see citing works
“This approach offers several advantages, includ-ingeaseofmanipulation,ef ﬁ cientcellulardelivery,greatertemporalcontrol, non-immunogenicity, and cost-effectiveness, making it more suitable for clinical development 30 .”
Recent progress of principal techniques used in the study of Müller glia reprogramming in mice
Yin, Z., Kang, J.-H., Xu, H.-A., Huo, S., & Xu, H.-W. (2024) · Cell Regeneration · doi:10.1186/s13619-024-00211-z · Cited by 2 · see citing works
“The visual cliff test examines stereoscopic vision by observing if the mice on the platform step towards the shallow or deep side (Wang et al. 2023a, b, c; Ji et al. 2022) (Fig.”
Chromatin landscape dynamics during reprogramming towards human naïve and primed pluripotency reveals the divergent function of PRDM1 isoforms
Zhou, J., Guo, M., Yang, G., Cui, X., Hu, J.-D., Lin, T., Wang, H., Gao, S.-R., Jiang, C.-Z., Wang, L.-P., et al. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02230-w · Cited by 2 · see citing works
“Several research groups have successfully generated iPSCs from diverse cell types by the ectopic expression of transcription factors or by the chemical stimulation of small molecules [1, 2].”
Chemical approaches targeting the hurdles of hepatocyte transplantation: mechanisms, applications, and advances
Shi, H., Ding, Y., Sun, P.-X., Lv, Z., Wang, C.-Y., Ma, H.-X., Lu, J.-Y., Yu, B., Li, W.-L., & Wang, C. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1480226 · Cited by 2 · see citing works
The regulation of stem cell fate and its application in neural regeneration
He, Y., Chen, X., He, M., & Li, Z. (2026) · Interdisciplinary Medicine · doi:10.1002/inmd.70137 · Cited by 1 · see citing works
Cellular reprogramming beyond pluripotency
Nuñez-Quintela, V., Li, H., & Collado, M. (2026) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2026.01.007 · Cited by 2 · see citing works
Regulation of cell reprogramming by engineered biomaterial-based biophysical cues for next-generation cell therapies
Zhang, S., Liu, S., Qin, Y., Zhao, S., & Liu, H. (2025) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2025.217309 · Cited by 1 · see citing works
Chemical reprogramming of fibroblasts into retinal pigment epithelium cells for vision restoration
Li, S.-S., Liu, H., Pan, S.-H., Zhu, Z., Zhang, S., Li, J.-H., Yao, Y.-H., Wang, X., Gao, N., Liu, X.-Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-67104-w · Cited by 1 · see citing works
The Influence of Short Peptides on Cell Senescence and Neuronal Differentiation
Sakhenberg, E., Linkova, N., Kraskovskaya, N., Krieger, D., Polyakova, V., Medvedev, D., Krasichkov, A., Khotin, M., & Ryzhak, G. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47090739 · Cited by 1 · see citing works
“However, cellular plasticity gradually declines during developmental progression [1].”
Developing chemical reprogramming strategies of non-hepatocytes for liver regeneration
Ge, D.-X., Yang, W.-Q., Ren, H.-Z., & Wang, J.-L. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.08.018 · Cited by 1 · see citing works
“It employs small molecules to modulate cellular signaling and gene expression with precision, thereby exerting control over cell function and fate, which is essential for tissue regeneration and repair [9].”
Self-citation
Regenerative Immunotherapy for Cancer: Transcription Factor Reprogramming of Tumor-Specific T Cells
McCaw, T. R., Restifo, N. P., Plath, K., & Crompton, J. G. (2025) · Cancers · doi:10.3390/cancers17132225 · Cited by 1 · see citing works
“With final product safety in mind, increasing incorporation of chemical reprogramming has been pursued as a strategy to improve safety and precisely tailor cell fate decisions [110].”
Advancing type 1 diabetes treatment: a breakthrough in stem cell therapy.
Anfaal, Z., & Khan, Z. (2025) · Diabetes & Metabolism · doi:10.1016/j.diabet.2025.101635 · Cited by 1 · see citing works
Small Molecular Approaches for Cellular Reprogramming and Tissue Engineering: Functions as Mediators of the Cell Signaling Pathway.
Parmar, B., & Bhatia, D. (2024) · Biochemistry · doi:10.1021/acs.biochem.4c00427 · Cited by 1 · see citing works
Patient-derived induced pluripotent stem cell organoids for amyotrophic lateral sclerosis drug discovery
Li, W.-Y., Liu, J.-Q., Li, W.-T., Sun, L.-N., Zhang, H., Gao, L., & Gao, C. (2025) · Acta Materia Medica · doi:10.15212/amm-2024-0077 · Cited by 1 · see citing works
“Reprogramming of donor cells independent of Yamanaka factors may provide an alternative method to optimize iPSC quality, such as chemical reprogramming and expanding pluripotent stem cells [83, 84].”
Methyl-donor inhibitors relax 3D genome structures to promote totipotent reprogramming.
Yang, T.-C., Li, L.-C., Zhao, J.-R., Cheng, R.-Q., Qi, Y.-Y., Bu, Y.-F., Chen, H.-B., Shi, M.-L., Xu, J., Deng, H.-K., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.118048
Self-citation
The crosstalk between alternative splicing and histone ubiquitination modulates fast chemical reprogramming to pluripotency
Deng, Q., Chen, X., Li, Y.-H., Wang, Y.-X., He, Y.-Q., Zhu, D., Chen, G., & Zhu, S.-Y. (2026) · Stem Cell Reports · doi:10.1016/j.stemcr.2026.103089
The evolution of iPSC-based cell therapy across autologous and allogeneic pathways
Wang, A., Zhang, Y., Deng, H.-K., & Gu, M.-X. (2026) · Cell Reports Medicine · doi:10.1016/j.xcrm.2026.102992
Self-citation
IRAK4 constrains cellular plasticity during chemically-induced cell fate reprogramming into multiple lineages
Huang, C.-S., Han, X.-Y., Wang, T., Zhao, Y., & Li, J. (2026) · EMBO Reports · doi:10.1038/s44319-026-00855-9
“…into pluripotent stem cells (CiPSCs) or lineage-speci ﬁ c cell types has emerged as a transformative strategy for regenerative medicine, bypassing ethical and technical limitations of traditional approaches (Guan et al, 2022; Hou et al, 2013; Wang et al, 2023; Yamanaka, 2020; Zhao et al, 2015).”
Optimized culture conditions enable sustainable proliferation and pluripotency of sheep embryonic stem cells
Jin, M., Song, S.-J., Liang, J., Li, L.-D., Zhang, K.-J., Shen, W., Kalds, P., Chen, Y.-L., & Wang, X.-L. (2026) · Journal of Integrative Agriculture · doi:10.1016/j.jia.2026.07.008
Regulation of small-molecule compounds on LC-PUFA biosynthesis during adipogenic transdifferentiation of Salmo salar muscle cells and preparation of cell-cultured fish fat.
Wei, Y., Hao, T.-T., Feng, Y.-M., Ji, P., Zhai, R., Dong, P., Xue, J., Li, Z.-J., Xue, C.-H., & Zheng, H.-W. (2026) · Food Research International · doi:10.1016/j.foodres.2026.120180
Hematopoietic Cell Fate Reprogramming in the Context of Pathological Processes and Translational Opportunities
Cirovic, B. (2026) · Cellular Reprogramming · doi:10.1177/21524971261464818
“In addition, replacement of experimental protocols requiring genetic manipulation with chemical cocktails would represent a major improvement in the ﬁ eld (E et al., 2025; Wang et al., 2023).”
Epigenetic Information Loss and Chronosenescence in Liver Aging: From Molecular Mechanisms to Therapeutic Interventions
Xu, X., Li, H., Li, J., & Huang, M. (2026) · The FASEB Journal · doi:10.1096/fj.202504570rr
“Recent breakthroughs identified small molecule combinations (chemical cocktails) through high-throughput screening [70].”
Orthogonal regulation of protein abundance.
He, W.-X., Han, M.-M., Qiao, W., Gao, C., Liu, L.-M., Wu, J., & Hu, G.-P. (2026) · TIBS -Trends in Biochemical Sciences. Regular ed · doi:10.1016/j.tibs.2026.04.013
Small Molecule Cocktail DLC79 Suppresses Gliomagenesis by Activating Ascl1 and Remodeling Transcriptome
Mao, C., Deng, Z., Chen, Z.-M., Huang, L.-R., Wang, C., Chen, G., & Wang, Q. (2026) · Cells · doi:10.3390/cells15020211
“Critically, small molecules present distinct pharmacological advantages over genetic TF delivery, offering precise temporal control, tunable dosing, multi-target engagement, and reduced immunogenicity [20,21].”
Edición Genética de las Células Madre con CRISPR-Cas: Avances en la Medicina Regenerativa
Sánchez, G. P. V., Villacís, I. S., & Ocaña, T. V. (2025) · Revista Científica Multidisciplinar G-nerando · doi:10.60100/rcmg.v6i2.894
In Vitro Generation of Brown and Beige Adipocytes via Cellular Reprogramming
Kurahashi, T., Harada, Y., & Dai, P. (2025) · Cellular Reprogramming · doi:10.1177/21524971251399164
“For clinical translation, chemically de ﬁ ned and quality-controlled compositions, as well as comprehensive pharmacokinetic, toxicological, and long-term tumorigenicity or biodistribution studies, will be indispensable — particularly for in vivo delivery (Kim et al., 2020; Wang et al., 2023).”
Trophectoderm-like cells from EPS cells enable generating EPS cell-derived post-implantation embryoids that complete gastrulation
Wang, X., Cheng, R.-Q., Wu, C.-Y., Liu, H.-Y., Li, Z.-N., Huo, Y.-F., Li, B., Zhao, D.-Y., Li, C., Deng, H.-K., et al. (2025) · Protein & Cell · doi:10.1093/procel/pwaf059
“…can be precisely fine-tuned in vitro in a spatio-temporal manner using small molecules, a strategy that has been shown to induce cellular fate changes across different lineages and stem cell types (Guan et al., 2022; Hou et al., 2013; Li et al., 2015; Liuyang et al., 2023; Wang et al., 2023).”
Self-citation
FAK signaling suppression by OCT4-ITGA6 mediates the effectively removal of residual pluripotent stem cells and enhances application safety
Song, W., Wang, J., Gong, S., Wang, X.-Y., Xu, J., Wu, R., Jiang, Z.-M., Zhang, H., Wu, L.-D., Wang, Y., et al. (2025) · Theranostics · doi:10.7150/thno.111198
“Pluripotent stem cells (PSCs), renowned for their capacity for unlimited self-renewal and differentiation into all three germ layers, have emerged as a promising cell source for regenerative therapies aimed at treating a wide range of diseases and injuries [1-3].”
Self-citation
Potential use of human pluripotency-related gene expression reporter cell line for screening small molecules to enhance induction of pluripotency
Ham, S., Lee, M., Jeong, D., Son, J., Kim, Y., Lee, T., Ko, K., Moh, S., & Ko, K. (2025) · BMB Reports · doi:10.5483/bmbrep.2024-0176
“Additionally, screening these chemicals enhances our understanding of the mechanisms involved in cellular reprogramming, providing crucial insights for advancing regenerative medicine (13, 14).”
5‐Aza combined with VPA reprograms human T lineage acute leukemia Jurkat cells into B‐cell‐like cells by epigenetic activation of PAX5
Xi, W.-J., Zheng, G.-X., Chen, X., Zuo, B.-L., Wang, W., Li, Y.-F., Zhang, C., Chu, J., Mu, X., Wen, W., et al. (2025) · Biotechnology progress (Print) · doi:10.1002/btpr.70023
Epigenetic mechanisms in stem cell therapies for achilles tendinopathy
Yuan, Z., Yao, Z., Mao, X., Gao, X., Wu, S., & Mao, H. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1516250
MEK inhibitor PD0325901 upregulates CD34 expression in endothelial cells via inhibition of ERK phosphorylation
Hosoda, C., Mitani, S., Sakata, A., Kasuda, S., Onodera, Y., Takabayashi, Y., Shima, M., & Tatsumi, K. (2024) · Regenerative Therapy · doi:10.1016/j.reth.2024.08.009

Authors: Wang, J., Sun, S., & Deng, H.
Affiliations: Peking University (CN)
Royal Children's Hospital (AU)
Corresponding author: Sun, Shicheng
Deng, Hongkui
ORCID: Wang, Jinlin
Sun, Shicheng
Deng, Hongkui
Venue: Cell Stem Cell
Publisher: Elsevier BV
Published: 2023-09
Volume: 30
Issue: 9
Pages: 1130-1147
ISSN: 1875-9777 (ISSN-L)
1934-5909
DOI: 10.1016/j.stem.2023.08.001
OpenAlex: W4386122826
Cited by: 91
References: 0
Citations by year: 2026: 17 · 2025: 45 · 2024: 27 · 2023: 2
FWCI: 2.41
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 372 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cell stem cell (publishedVersion)
PubMed (publishedVersion)
Funders: National Natural Science Foundation of China (32288102)
China Postdoctoral Science Foundation (YJ20220249)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords: chemical reprogramming, somatic cell reprogramming, pluripotent stem cells, totipotency, stem cell state, clinical translation
MeSH terms: Cell Differentiation, Humans, Pluripotent Stem Cells

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Chemical reprogramming for cell fate manipulation: Methods, applications, and perspectives

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