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Direct conversion of fibroblasts to functional neurons by defined factors
Open accessAbstract
Cellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. Recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription factors could directly induce other defined somatic cell fates, and not only an undifferentiated state. We hypothesized that combinatorial expression of neural-lineage-specific transcription factors could directly convert fibroblasts into neurons. Starting from a pool of nineteen candidate genes, we identified a combination of only three factors, Ascl1, Brn2 (also called Pou3f2) and Myt1l, that suffice to rapidly and efficiently convert mouse embryonic and postnatal fibroblasts into functional neurons in vitro. These induced neuronal (iN) cells express multiple neuron-specific proteins, generate action potentials and form functional synapses. Generation of iN cells from non-neural lineages could have important implications for studies of neural development, neurological disease modelling and regenerative medicine.
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“Viral screens using focused overexpression libraries can identify putative reprogramming factors, for example, by identifying a defined set of transcription factors that are selectively required to induce pluripotent stem cells (2–4,7) or trans-differentiate from mature somatic cell into another mature somatic cell (1,8–11).”
From Establishment of single-cell screening system for the rapid identification of transcriptional modulators involved in direct cell reprogramming (2012) · cites this paper as [10]
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“Despite the power of viral technologies, pooled screens for cell reprogramming have generally adopted a one-by-one elimination approach or testing for exhaustive combinations and interrogating phenotypes in cell culture from transgenic mice (1,3,10) and/or aberrantly cloned cell lines (12).”
From Establishment of single-cell screening system for the rapid identification of transcriptional modulators involved in direct cell reprogramming (2012) · cites this paper as [10]
In the citing paper
“Furthermore, iPSC-derived cell types from different lineages can be combined into defined three-dimensional cultures, termed assembloids9,94–98.”
From CRISPR-based functional genomics for neurological disease (2020) · cites this paper as [98]
In the citing paper
“MYT1L is a myelin transcription factor required to convert mouse embryonic and postnatal fibroblasts into functional neurons [68].”
From Genetic and Functional Analyses of SHANK2 Mutations Suggest a Multiple Hit Model of Autism Spectrum Disorders (2012) · cites this paper as [68]
In the citing paper
“Functional induced neurons (iN) can be generated directly from fibroblasts by forced expression of neural specific transcription factors, a process also called transdifferentiation (Vierbuchen et al., 2010).”
From Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation (2016) · cites this paper as Vierbuchen et al., 2010
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Citations
Cites
Takahashi, K., & Yamanaka, S. (2006) · Cell · doi:10.1016/j.cell.2006.07.024 · Cited by 26,673
Jenuwein, T., & Allis, C. D. (2001) · Science · doi:10.1126/science.1063127 · Cited by 9,756
Chen, X., Xiu, M., Xing, J., Yu, S., Min, D., & Guo, F. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479439 · Cited by 5,760
Expression of a single transfected cDNA converts fibroblasts to myoblasts
Davis, R. L., Weintraub, H. M., & Lassar, A. B. (1987) · Cell · doi:10.1016/0092-8674(87)90585-x · Cited by 3,388
Bernstein, B. E., Meissner, A., & Lander, E. S. (2007) · Cell · doi:10.1016/j.cell.2007.01.033 · Cited by 2,086
In vivo reprogramming of adult pancreatic exocrine cells to β-cells
Zhou, Q., Brown, J., Kanarek, A., Rajagopal, J., & Melton, D. A. (2008) · Nature · doi:10.1038/nature07314 · Cited by 2,010
Sheep cloned by nuclear transfer from a cultured cell line
Campbell, K., McWhir, J., Ritchie, W. A., & Wilmut, I. (1996) · Nature · doi:10.1038/380064a0 · Cited by 1,868
Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis
Christopherson, K. S., Ullian, E. M., Stokes, C. C. A., Mullowney, C. E., Hell, J. W., Agah, A., Lawler, J., Mosher, D. F., Bornstein, P., & Barres, B. A. (2005) · Cell · doi:10.1016/j.cell.2004.12.020 · Cited by 1,688
Stem Cells, the Molecular Circuitry of Pluripotency and Nuclear Reprogramming
Jaenisch, R., & Young, R. A. (2008) · Cell · doi:10.1016/j.cell.2008.01.015 · Cited by 1,465
Transplantation of living nuclei from blastula cells into enucleated frogs’ eggs
Briggs, R., & King, T. J. (1952) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.38.5.455 · Cited by 1,127
Guillemot, F., Lo, L., Johnson, J. E. B., Auerbach, A. B., Anderson, D. J., & Joyner, A. L. (1993) · Cell · doi:10.1016/0092-8674(93)90381-y · Cited by 1,032
Conversion of Xenopus Ectoderm into Neurons by NeuroD, a Basic Helix-Loop-Helix Protein
Lee, J. E., Hollenberg, S. M., Snider, L., Turner, D. L., Lipnick, N., & Weintraub, H. (1995) · Science · doi:10.1126/science.7754368 · Cited by 1,023
Stepwise Reprogramming of B Cells into Macrophages
Xie, H., Ye, M., Feng, R., & Graf, T. (2004) · Cell · doi:10.1016/s0092-8674(04)00419-2 · Cited by 987
Nuclear Reprogramming of Somatic Cells After Fusion with Human Embryonic Stem Cells
Cowan, C. A., Atienza, J., Melton, D. A., & Eggan, K. C. (2005) · Science · doi:10.1126/science.1116447 · Cited by 932
Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells
Tada, M., Takahama, Y., Abe, K., Nakatsuji, N., & Tada, T. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00459-6 · Cited by 891
Direct Reprogramming of Terminally Differentiated Mature B Lymphocytes to Pluripotency
Hanna, J. H., Markoulaki, S., Schorderet, P., Carey, B. W., Beard, C., Wernig, M., Creyghton, M. P., Steine, E. J., Cassady, J. P., Foreman, R. K., et al. (2008) · Cell · doi:10.1016/j.cell.2008.03.028 · Cited by 830
Self-citationSexually Mature Individuals of Xenopus laevis from the Transplantation of Single Somatic Nuclei
Gurdon, J. B., Elsdale, T., & Fischberg, M. (1958) · Nature · doi:10.1038/182064a0 · Cited by 609
Monoclonal mice generated by nuclear transfer from mature B and T donor cells
Hochedlinger, K., & Jaenisch, R. (2002) · Nature · doi:10.1038/nature718 · Cited by 536
Elite and stochastic models for induced pluripotent stem cell generation
Yamanaka, S. (2009) · Nature · doi:10.1038/nature08180 · Cited by 524
Conversion of mature B cells into T cells by dedifferentiation to uncommitted progenitors
Cobaleda, C., Jochum, W., & Busslinger, M. (2007) · Nature · doi:10.1038/nature06159 · Cited by 502
Beard, C., Hochedlinger, K., Plath, K., Wutz, A., & Jaenisch, R. (2006) · genesis · doi:10.1002/gene.20180 · Cited by 482
Neurotrophins are required for nerve growth during development
Tucker, K. L., Meyer, M., & Barde, Y.-A. (2001) · Nature Neuroscience · doi:10.1038/82868 · Cited by 477
Generation of neurons by transient expression of neural bHLH proteins in mammalian cells
Farah, M. H., Olson, J. M., Sucic, H. B., Hume, R. I., Tapscott, S. J., & Turner, D. L. (2000) · Development · doi:10.1242/dev.127.4.693 · Cited by 472
A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types
Wernig, M., Lengner, C. J., Hanna, J. H., Lodato, M. A., Steine, E. J., Foreman, R. K., Staerk, J., Markoulaki, S., & Jaenisch, R. (2008) · Nature Biotechnology · doi:10.1038/nbt1483 · Cited by 445
Self-citationSilva, J., & Smith, A. G. (2008) · Cell · doi:10.1016/j.cell.2008.02.006 · Cited by 418
Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines
Kondo, M., Scherer, D. C., Miyamoto, T., King, A. G., Akashi, K., Sugamura, K., & Weissman, I. L. (2000) · Nature · doi:10.1038/35030112 · Cited by 382
PU.1 and C/EBPα/β convert fibroblasts into macrophage-like cells
Feng, R., Desbordes, S. C., Xie, H., Tillo, E. S., Pixley, F., Stanley, E. R., & Graf, T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711961105 · Cited by 348
Nuclei of Embryonic Stem Cells Reprogram Somatic Cells
Tae, J., & Schöler, H. R. (2004) · Stem Cells · doi:10.1634/stemcells.22-6-941 · Cited by 275
Escurat, M., Djabali, K., Gumpel, M., Gros, F., & Portier, M. (1990) · Journal of Neuroscience · doi:10.1523/jneurosci.10-03-00764.1990 · Cited by 256
Extreme Makeover: Converting One Cell into Another
Zhou, Q., & Melton, D. A. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.09.015 · Cited by 255
Maximov, A., & Südhof, T. C. (2005) · Neuron · doi:10.1016/j.neuron.2005.09.006 · Cited by 238
Self-citationCellular and molecular control of neurogenesis in the mammalian telencephalon
Guillemot, F. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.09.006 · Cited by 196
A Robust and Highly Efficient Immune Cell Reprogramming System
Bussmann, L. H., Schubert, A., Manh, T. V., de Andrés-Aguayo, L., Desbordes, S. C., Parra, M., Zimmermann, T., Rapino, F. A., Rodríguez‐Ubreva, J., Ballestar, E., et al. (2009) · Cell stem cell · doi:10.1016/j.stem.2009.10.004 · Cited by 171
Effect of cell history on response to helix–loop–helix family of myogenic regulators
Schäfer, B. W., Blakely, B. T., Darlington, G., & Blau, H. M. (1990) · Nature · doi:10.1038/344454a0 · Cited by 151
Wu, H., Xu, J., Pang, Z. P., Ge, W., Kim, K. J., Blanchi, B., Chen, C., Südhof, T. C., & Sun, Y. E. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706199104 · Cited by 142
Self-citationMonitoring synaptic transmission in primary neuronal cultures using local extracellular stimulation
Maximov, A., Pang, Z. P., Tervo, D. G. R., & Südhof, T. C. (2006) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2006.10.009 · Cited by 138
Self-citationTau EGFP embryonic stem cells: An efficient tool for neuronal lineage selection and transplantation
Wernig, M., Tucker, K. L., Gornik, V., Schneiders, A. M., Buschwald, R., Wiestler, O. D., Barde, Y., & Brüstle, O. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10395 · Cited by 86
Self-citationHow fixed is the differentiated state?
Blau, H. M. (1989) · Trends in Genetics · doi:10.1016/0168-9525(89)90100-5 · Cited by 75
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Ieda, M., Fu, J.-D., Delgado-Olguin, P., Vedantham, V., Hayashi, Y., Bruneau, B. G., & Srivastava, D. (2010) · Cell · doi:10.1016/j.cell.2010.07.002 · Cited by 2,454
Rapid single-step induction of functional neurons from human pluripotent stem cells
Zhang, Y., Pak, C., Han, Y., Ahlenius, H., Zhang, Z., Chanda, S., Marro, S., Patzke, C., Acuna, C., Covy, J., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.05.029 · Cited by 1,644
Self-citationTranscriptional Regulation and Its Misregulation in Disease
Lee, T. I., & Young, R. A. (2013) · Cell · doi:10.1016/j.cell.2013.02.014 · Cited by 1,676
Emerging trends in regenerative medicine: a scientometric analysis inCiteSpace
Chen, C., Hu, Z., Liu, S., & Tseng, H. (2012) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2012.674507 · Cited by 1,413
In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes
Li, Q., Huang, Y., Spencer, C. I., Foley, A., Vedantham, V., Liu, L., Conway, S. J., Fu, J., & Srivastava, D. (2012) · Nature · doi:10.1038/nature11044 · Cited by 1,376
Metadata
- Authors
- Vierbuchen, T., Ostermeier, A., Pang, Z. P., Kokubu, Y., Südhof, T. C., & Wernig, M.
- Affiliations
- Institute for Stem Cell Biology and Regenerative Medicine (IN)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Wernig, Marius
- Venue
- Nature
- Published
- 2010-01-27
- Volume
- 463
- Issue
- 7284
- Pages
- 1035-1041
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2829121
- OpenAlex
- W2136541538
- Cited by
- 3,017
- References
- 38
- Citations by year
- 2026: 84 · 2025: 97 · 2024: 87 · 2023: 135 · 2022: 140 · 2021: 148 · 2020: 148 · 2019: 165 · 2018: 192 · 2017: 211 · 2016: 224 · 2015: 232 · 2014: 231 · 2013: 272 · 2012: 253
- FWCI
- 119.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (5t32ns007280-35)
- U.S. Public Health Service (1018438-142-PABCA)
- National Heart, Lung, and Blood Institute (U01HL100397)
- National Cancer Institute (T32CA009302)
- National Institute of Neurological Disorders and Stroke (T32NS-007280, 5T32NS007280)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- ASCL1, Brn2, MYT1L, action potential, induced pluripotent stem cells, regenerative medicine
- MeSH terms
- Oligodendrocyte Transcription Factor 2, Action Potentials, Animals, Cell Line, Cells, Cultured, Embryo, Mammalian, Fibroblasts, Nerve Tissue Proteins, Neurons, Synapses, Tail, Time Factors, Transcription Factors, Biomarkers, Cell Lineage, Regenerative Medicine, POU Domain Factors, Mice, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Cell Transdifferentiation
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