Small molecules enable neurogenin 2 to efficiently convert human fibroblasts into cholinergic neurons

Nature Communications

Volumn 4, Issue , 2013, Pages

  Liu, Meng Lu ^a   Zang, Tong ^a   Zou, Yuhua ^a   Chang, Joshua C ^b   Gibson, Jay R ^b   Huber, Kimberly M ^b   Zhang, Chun Li ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DORSOMORPHIN; ENZYME INHIBITOR; FORSKOLIN; NEUROGENIN 2; TRANSCRIPTION FACTOR SOX11; UNCLASSIFIED DRUG;

CELL ORGANELLE; GENE EXPRESSION; MOLECULAR ANALYSIS; MUSCLE; NEUROLOGY; PHYSIOLOGY;

ARTICLE; CELL STRUCTURE; CHOLINERGIC NERVE CELL; CONTROLLED STUDY; ELECTROPHYSIOLOGY; FIBROBLAST; GENE EXPRESSION; HUMAN; HUMAN CELL; LUNG FIBROBLAST; MOTONEURON; NERVE CELL PLASTICITY; NERVE FIBER GROWTH; NEUROMUSCULAR SYNAPSE; PROTEIN EXPRESSION; SKIN FIBROBLAST; TRANSCRIPTOMICS;

ACTION POTENTIALS; ADULT; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; CELL DIFFERENTIATION; CHOLINERGIC NEURONS; COLFORSIN; FETUS; FIBROBLASTS; GENE EXPRESSION; GENES, REPORTER; GREEN FLUORESCENT PROTEINS; HUMANS; LUNG; NERVE TISSUE PROTEINS; NEUROMUSCULAR JUNCTION; PRIMARY CELL CULTURE; PYRAZOLES; PYRIMIDINES; SOXC TRANSCRIPTION FACTORS; TIME FACTORS;

EID: 84880849098     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms3183     Document Type: Article

References (47)

1. Hanna, J. H., Saha, K. & Jaenisch, R. Pluripotency and cellular reprogramming: facts, hypotheses, unresolved issues. Cell 143, 508-525 (2010).
2. Ladewig, J. et al. Small molecules enable highly efficient neuronal conversion of human fibroblasts. Nat. Methods 9, 575-578 (2012).
3. Marro, S. et al. Direct lineage conversion of terminally differentiated hepatocytes to functional neurons. Cell Stem Cell 9, 374-382 (2011).
4. Son, E. Y. et al. Conversion of mouse and human fibroblasts into functional spinal motor neurons. Cell Stem Cell 9, 205-218 (2011).
5. Caiazzo, M. et al. Direct generation of functional dopaminergic neurons from mouse and human fibroblasts. Nature 476, 224-227 (2011).
6. Pfisterer, U. et al. Direct conversion of human fibroblasts to dopaminergic neurons. Proc. Natl Acad. Sci. USA 108, 10343-10348 (2011).
7. Vierbuchen, T. et al. Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463, 1035-1041 (2010).
8. Ambasudhan, R. et al. Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions. Cell Stem Cell 9, 113-118 (2011).
9. Qiang, L. et al. Directed conversion of Alzheimer's disease patient skin fibroblasts into functional neurons. Cell 146, 359-371 (2011).
10. Pang, Z. P. et al. Induction of human neuronal cells by defined transcription factors. Nature 476, 220-223 (2011).
11. Liu, X. et al. Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells. Cell Res. 22, 321-332 (2012).
12. Kim, J. et al. Functional integration of dopaminergic neurons directly converted from mouse fibroblasts. Cell Stem Cell 9, 413-419 (2011).
13. Yoo, A. S. et al. MicroRNA-mediated conversion of human fibroblasts to neurons. Nature 476, 228-231 (2011).
14. Heinrich, C. et al. Directing astroglia from the cerebral cortex into subtype specific functional neurons. PLoS Biol. 8, e1000373 (2010).
15. Meng, F. et al. Induction of fibroblasts to neurons through adenoviral gene delivery. Cell Res. 22, 436-440 (2012).
16. Mizuguchi, R. et al. Combinatorial roles of olig2 and neurogenin2 in the coordinated induction of pan-neuronal and subtype-specific properties of motoneurons. Neuron 31, 757-771 (2001).
17. Sun, Y. et al. Neurogenin promotes neurogenesis and inhibits glial differentiation by independent mechanisms. Cell 104, 365-376 (2001).
18. Ross, S. E., Greenberg, M. E. & Stiles, C. D. Basic helix-loop-helix factors in cortical development. Neuron 39, 13-25 (2003).
19. Lee, S., Lee, B., Lee, J. W. & Lee, S. K. Retinoid signaling and neurogenin2 function are coupled for the specification of spinal motor neurons through a chromatin modifier CBP. Neuron 62, 641-654 (2009).
20. Scardigli, R., Schuurmans, C., Gradwohl, G. & Guillemot, F. Crossregulation between Neurogenin2 and pathways specifying neuronal identity in the spinal cord. Neuron 31, 203-217 (2001).
21. Ma, Y. C. et al. Regulation of motor neuron specification by phosphorylation of neurogenin 2. Neuron 58, 65-77 (2008).
22. Lee, S. K. & Pfaff, S. L. Synchronization of neurogenesis and motor neuron specification by direct coupling of bHLH and homeodomain transcription factors. Neuron 38, 731-745 (2003).
23. Rouaux, C. & Arlotta, P. Fezf2 directs the differentiation of corticofugal neurons from striatal progenitors in vivo. Nat. Neurosci. 13, 1345-1347 (2010).
24. Chen, B. et al. The Fezf2-Ctip2 genetic pathway regulates the fate choice of subcortical projection neurons in the developing cerebral cortex. Proc. Natl Acad. Sci. USA 105, 11382-11387 (2008).
25. Peljto, M., Dasen, J. S., Mazzoni, E. O., Jessell, T. M. & Wichterle, H. Functional diversity of ESC-derived motor neuron subtypes revealed through intraspinal transplantation. Cell Stem Cell 7, 355-366 (2010).
26. Dasen, J. S., De Camilli, A., Wang, B., Tucker, P. W. & Jessell, T. M. Hox repertoires for motor neuron diversity and connectivity gated by a single accessory factor, FoxP1. Cell 134, 304-316 (2008).
27. Dasen, J. S., Liu, J. P. & Jessell, T. M. Motor neuron columnar fate imposed by sequential phases of Hox-c activity. Nature 425, 926-933 (2003).
28. Dasen, J. S., Tice, B. C., Brenner-Morton, S. & Jessell, T. M. A Hox regulatory network establishes motor neuron pool identity and target-muscle connectivity. Cell 123, 477-491 (2005).
29. Hester, M. E. et al. Rapid and efficient generation of functional motor neurons from human pluripotent stem cells using gene delivered transcription factor codes. Mol. Ther. 19, 1905-1912 (2011).
30. Wichterle, H., Lieberam, I., Porter, J. A. & Jessell, T. M. Directed differentiation of embryonic stem cells into motor neurons. Cell 110, 385-397 (2002).
31. Thein, D. C. et al. The closely related transcription factors Sox4 and Sox11 function as survival factors during spinal cord development. J. Neurochem. 115, 131-141 (2010).
32. Grothe, C., Wewetzer, K., Lagrange, A. & Unsicker, K. Effects of basic fibroblast growth factor on survival and choline acetyltransferase development of spinal cord neurons. Brain Res. Dev. Brain Res. 62, 257-261 (1991).
33. Hughes, R. A., Sendtner, M. & Thoenen, H. Members of several gene families influence survival of rat motoneurons in vitro and in vivo. J. Neurosci. Res. 36, 663-671 (1993).
34. Teng, Y. D., Mocchetti, I., Taveira-DaSilva, A. M., Gillis, R. A. & Wrathall, J. R. Basic fibroblast growth factor increases long-term survival of spinal motor neurons and improves respiratory function after experimental spinal cord injury. J. Neurosci. 19, 7037-7047 (1999).
35. Mu, L. et al. SoxC transcription factors are required for neuronal differentiation in adult hippocampal neurogenesis. J. Neurosci. 32, 3067-3080 (2012).
36. Shim, S., Kwan, K. Y., Li, M., Lefebvre, V. & Sestan, N. Cis-regulatory control of corticospinal system development and evolution. Nature 486, 74-79 (2012).
37. Jordan, P. M. et al. Generation of spinal motor neurons from human fetal brain-derived neural stem cells: role of basic fibroblast growth factor. J. Neurosci. Res 87, 318-332 (2009).
38. Jo, A. Y., Park, C. H., Aizawa, S. & Lee, S. H. Contrasting and brain regionspecific roles of neurogenin2 and mash1 in GABAergic neuron differentiation in vitro. Exp. Cell Res. 313, 4066-4081 (2007).
39. Parras, C. M. et al. Divergent functions of the proneural genes Mash1 and Ngn2 in the specification of neuronal subtype identity. Genes Dev. 16, 324-338 (2002).
40. Bergsland, M., Werme, M., Malewicz, M., Perlmann, T. & Muhr, J. The establishment of neuronal properties is controlled by Sox4 and Sox11. Genes Dev. 20, 3475-3486 (2006).
41. Lee, S. K. & Pfaff, S. L. Transcriptional networks regulating neuronal identity in the developing spinal cord. Nat. Neurosci. 4, 1183-1191 (2001).
42. Kim, J. et al. Direct reprogramming of mouse fibroblasts to neural progenitors. Proc. Natl Acad. Sci. USA 108, 7838-7843 (2011).
43. Ring, K. L. et al. Direct reprogramming of mouse and human fibroblasts into multipotent neural stem cells with a single factor. Cell Stem Cell 11, 100-109 (2012).
44. Han, D. W. et al. Direct reprogramming of fibroblasts into neural stem cells by defined factors. Cell Stem Cell 10, 465-472 (2012).
45. Lujan, E., Chanda, S., Ahlenius, H., Sudhof, T. C. & Wernig, M. Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cells. Proc. Natl Acad. Sci. USA 109, 2527-2532 (2012).
46. Thier, M. et al. Direct conversion of fibroblasts into stably expandable neural stem cells. Cell Stem Cell 10, 473-479 (2012).
47. Niu, W., Zou, Y., Shen, C. & Zhang, C. L. Activation of postnatal neural stem cells requires nuclear receptor TLX. J. Neurosci. 31, 13816-13828 (2011).