Characterizing human stem cell-derived sensory neurons at the single-cell level reveals their ion channel expression and utility in pain research

Molecular Therapy

Volumn 22, Issue 8, 2014, Pages 1530-1543

  Young, Gareth T ^a   Gutteridge, Alex ^a   Fox, Heather D E ^a,b   Wilbrey, Anna L ^a   Cao, Lishuang ^a   Cho, Lily T ^a   Brown, Adam R ^a   Benn, Caroline L ^a   Kammonen, Laura R ^a   Friedman, Julia H ^c   Bictash, Magda ^a   Whiting, Paul ^a   Bilsland, James G ^a   Stevens, Edward B ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ION CHANNEL; NEUROGENIN 1; NEUROGENIN 2; OCTAMER TRANSCRIPTION FACTOR 4; PERIPHERIN; POTASSIUM CHANNEL KCNQ2; POTASSIUM CHANNEL KCNQ3; SMAD PROTEIN; SODIUM CHANNEL NAV1.7; TRANSCRIPTION FACTOR MSX1; TRANSCRIPTION FACTOR NANOG; TRANSCRIPTION FACTOR PAX6; TRANSCRIPTION FACTOR POU4F1; TRANSCRIPTION FACTOR RUNX1; A 803467; ANILINE DERIVATIVE; FORSKOLIN; FURAN DERIVATIVE;

ARTICLE; CELL DIFFERENTIATION; CELL POPULATION; CONTROLLED STUDY; EMBRYONIC STEM CELL; EVOKED RESPONSE; GENE; GENE EXPRESSION; HUMAN; HUMAN CELL; MEMBRANE STEADY POTENTIAL; MSX1 GENE; NANOG GENE; NERVE EXCITABILITY; NERVE FIBER GROWTH; NEUROG1 GENE; NEUROG2 GENE; NOCICEPTION; NTRK1 GENE; PAIN; PAX6 GENE; PHENOTYPE; POU5F1 GENE; PROTEIN EXPRESSION; SCN9A GENE; SENSORY NERVE CELL; SINGLE CELL ANALYSIS; TAC1 GENE; CELL CULTURE; CYTOLOGY; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY; PLURIPOTENT STEM CELL; SPINAL GANGLION;

RODENTIA;

ANILINE COMPOUNDS; CELL DIFFERENTIATION; CELLS, CULTURED; COLFORSIN; FURANS; GANGLIA, SPINAL; GENE EXPRESSION REGULATION; HUMANS; ION CHANNELS; PAIN; PLURIPOTENT STEM CELLS; SENSORY RECEPTOR CELLS; SINGLE-CELL ANALYSIS;

EID: 84905491563     PISSN: 15250016     EISSN: 15250024     Source Type: Journal    
DOI: 10.1038/mt.2014.86     Document Type: Article

References (54)

1. Robinton, DA and Daley, GQ (2012). The promise of induced pluripotent stem cells in research and therapy. Nature 481: 295-305.
2. Chambers, SM, Fasano, CA, Papapetrou, EP, Tomishima, M, Sadelain, M and Studer, L (2009). Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 27: 275-280.
3. Maroof, AM, Keros, S, Tyson, JA, Ying, SW, Ganat, YM, Merkle, FT et al. (2013). Directed differentiation and functional maturation of cortical interneurons from human embryonic stem cells. Cell Stem Cell 12: 559-572.
4. Dage, JL, Colvin, EM, Fouillet, A, Langron, E, Roell, WC, Li, J et al. (2014). Pharmacological characterisation of ligand- and voltage-gated ion channels expressed in human iPSC-derived forebrain neurons. Psychopharmacology (Berl) 231: 1105-1124.
5. Park, S, Lee, KS, Lee, YJ, Shin, HA, Cho, HY, Wang, KC et al. (2004). Generation of dopaminergic neurons in vitro from human embryonic stem cells treated with neurotrophic factors. Neurosci Lett 359: 99-103.
6. Perrier, AL, Tabar, V, Barberi, T, Rubio, ME, Bruses, J, Topf, N et al. (2004). Derivation of midbrain dopamine neurons from human embryonic stem cells. Proc Natl Acad Sci USA 101: 12543-12548.
7. Kriks, S, Shim, JW, Piao, J, Ganat, YM, Wakeman, DR, Xie, Z et al. (2011). Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease. Nature 480: 547-551.
8. Dimos, JT, Rodolfa, KT, Niakan, KK, Weisenthal, LM, Mitsumoto, H, Chung, W et al. (2008). Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321: 1218-1221.
9. Chambers, SM, Qi, Y, Mica, Y, Lee, G, Zhang, XJ, Niu, L et al. (2012). Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors. Nat Biotechnol 30: 715-720.
10. Guo, X, Spradling, S, Stancescu, M, Lambert, S and Hickman, JJ (2013). Derivation of sensory neurons and neural crest stem cells from human neural progenitor hNP1. Biomaterials 34: 4418-4427.
11. Surmacz, B, Fox, H, Gutteridge, A, Fish, P, Lubitz, S and Whiting, P (2012). Directing differentiation of human embryonic stem cells toward anterior neural ectoderm using small molecules. Stem Cells 30: 1875-1884.
12. Lukk, M, Kapushesky, M, Nikkilä, J, Parkinson, H, Goncalves, A, Huber, W et al. (2010). A global map of human gene expression. Nat Biotechnol 28: 322-324.
13. Ringnér, M (2008). What is principal component analysis? Nat Biotechnol 26: 303-304.
14. Goeman, JJ and Bühlmann, P (2007). Analyzing gene expression data in terms of gene sets: methodological issues. Bioinformatics 23: 980-987.
15. Tian, L, Greenberg, SA, Kong, SW, Altschuler, J, Kohane, IS and Park, PJ (2005). Discovering statistically significant pathways in expression profiling studies. Proc Natl Acad Sci USA 102: 13544-13549.
16. Wu, D, Lim, E, Vaillant, F, Asselin-Labat, ML, Visvader, JE and Smyth, GK (2010). ROAST: rotation gene set tests for complex microarray experiments. Bioinformatics 26: 2176-2182.
17. Boyer, LA, Lee, TI, Cole, MF, Johnstone, SE, Levine, SS, Zucker, JP et al. (2005). Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122: 947-956.
18. Lallemend, F and Ernfors, P (2012). Molecular interactions underlying the specification of sensory neurons. Trends Neurosci 35: 373-381.
19. Stanke, M, Junghans, D, Geissen, M, Goridis, C, Ernsberger, U and Rohrer, H (1999). The Phox2 homeodomain proteins are sufficient to promote the development of sympathetic neurons. Development 126: 4087-4094.
20. Leon, TY, Ngan, ES, Poon, HC, So, MT, Lui, VC, Tam, PK et al. (2009). Transcriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3. J Pediatr Surg 44: 1904-1912.
21. Burau, K, Stenull, I, Huber, K, Misawa, H, Berse, B, Unsicker, K et al. (2004). c-ret regulates cholinergic properties in mouse sympathetic neurons: evidence from mutant mice. Eur J Neurosci 20: 353-362.
22. Reynolds, A, Richards, G, de la Iglesia, B and Rayward-Smith, V. (2006) Clustering rules: a comparison of partitioning and hierarchical clustering algorithms. J Math Model Algor 5, 475-504.
23. Maddox, FN, Valeyev, AY, Poth, K, Holohean, AM, Wood, PM, Davidoff, RA et al. (2004). GABAA receptor subunit mRNA expression in cultured embryonic and adult human dorsal root ganglion neurons. Brain Res Dev Brain Res 149: 143-151.
24. Valeyev, AY, Hackman, JC, Holohean, AM, Wood, PM, Katz, JL and Davidoff, RA (1999). GABA-Induced Cl- current in cultured embryonic human dorsal root ganglion neurons. J Neurophysiol 82: 1-9.
25. White, G (1990). GABAA-receptor-activated current in dorsal root ganglion neurons freshly isolated from adult rats. J Neurophysiol 64: 57-63.
26. Witschi, R, Punnakkal, P, Paul, J, Walczak, JS, Cervero, F, Fritschy, JM et al. (2011). Presynaptic alpha2-GABAA receptors in primary afferent depolarization and spinal pain control. J Neurosci 31: 8134-8142.
27. Postea, O and Biel, M (2011). Exploring HCN channels as novel drug targets. Nat Rev Drug Discov 10: 903-914.
28. Emery, EC, Young, GT and McNaughton, PA (2012). HCN2 ion channels: an emerging role as the pacemakers of pain. Trends Pharmacol Sci 33: 456-463.
29. Stieber, J, Wieland, K, Stöckl, G, Ludwig, A and Hofmann, F (2006). Bradycardic and proarrhythmic properties of sinus node inhibitors. Mol Pharmacol 69: 1328-1337.
30. Passmore, GM, Selyanko, AA, Mistry, M, Al-Qatari, M, Marsh, SJ, Matthews, EA et al. (2003). KCNQ/M currents in sensory neurons: significance for pain therapy. J Neurosci 23: 7227-7236.
31. Yu, H, Wu, M, Townsend, SD, Zou, B, Long, S, Daniels JS et al. Discovery, synthesis, and structure-activity relationship of a series of N-Aryl-bicyclo[2. 2. 1]heptane-2- carboxamides: characterization of ML213 as a novel KCNQ2 and KCNQ4 potassium channel opener. ACS Chem Neurosci 2, 572-577 (2011).
32. Bialer, M, Johannessen, SI, Levy, RH, Perucca, E, Tomson, T and White, HS (2010). Progress report on new antiepileptic drugs: a summary of the Tenth Eilat Conference (EILAT X). Epilepsy Res 92: 89-124.
33. Smith, ES, Cadiou, H and McNaughton, PA (2007). Arachidonic acid potentiates acid-sensing ion channels in rat sensory neurons by a direct action. Neuroscience 145: 686-698.
34. Cadiou, H, Studer, M, Jones, NG, Smith, ES, Ballard, A, McMahon, SB et al. (2007). Modulation of acid-sensing ion channel activity by nitric oxide. J Neurosci 27: 13251-13260.
35. Diochot, S, Baron, A, Salinas, M, Douguet, D, Scarzello, S, Dabert-Gay, AS et al. (2012). Black mamba venom peptides target acid-sensing ion channels to abolish pain. Nature 490: 552-555.
36. Moignard, V, Macaulay, IC, Swiers, G, Buettner, F, Schütte, J, Calero-Nieto, FJ et al. (2013). Characterization of transcriptional networks in blood stem and progenitor cells using high-throughput single-cell gene expression analysis. Nat Cell Biol 15: 363-372.
37. Glebova, NO and Ginty, DD (2005). Growth and survival signals controlling sympathetic nervous system development. Annu Rev Neurosci 28: 191-222.
38. Yan, L, Yang, M, Guo, H, Yang, L, Wu, J, Li, R et al. (2013) Single-cell RNA-Seq profiling of human preimplantation embryos and embryonic stem cells. Nature Structural & Molecular Biol 20: 1131-1139.
39. Xue, Z, Huang, K, Cai, C, Cai, L, Jiang, C-Y, Feng, Y et al. (2013) Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing. Nature 500: 593-597.
40. McKernan, RM, Rosahl, TW, Reynolds, DS, Sur, C, Wafford, KA, Atack, JR et al. (2000). Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype. Nat Neurosci 3: 587-592.
41. Wickenden, AD, Maher, MP and Chaplan, SR (2009). HCN pacemaker channels and pain: a drug discovery perspective. Curr Pharm Des 15: 2149-2168.
42. Emery, EC, Young, GT, Berrocoso, EM, Chen, L and McNaughton, PA (2011). HCN2 ion channels play a central role in inflammatory and neuropathic pain. Science 333: 1462-1466.
43. Bucchi, A, Tognati, A, Milanesi, R, Baruscotti, M and DiFrancesco, D (2006). Properties of ivabradine-induced block of HCN1 and HCN4 pacemaker channels. J Physiol (Lond) 572(Pt 2): 335-346.
44. Momin, A, Cadiou, H, Mason, A and McNaughton, PA (2008). Role of the hyperpolarization-activated current Ih in somatosensory neurons. J Physiol (Lond) 586(Pt 24): 5911-5929.
45. Hirano, K, Kuratani, K, Fujiyoshi, M, Tashiro, N, Hayashi, E and Kinoshita, M (2007). Kv7. 2-7. 5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice. Neurosci Lett 413: 159-162.
46. Blackburn-Munro, G and Jensen, BS (2003). The anticonvulsant retigabine attenuates nociceptive behaviours in rat models of persistent and neuropathic pain. Eur J Pharmacol 460: 109-116.
47. Escoubas, P, De Weille, JR, Lecoq, A, Diochot, S, Waldmann, R, Champigny, G et al. (2000). Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels. J Biol Chem 275: 25116-25121.
48. Diochot, S, Baron, A, Rash, LD, Deval, E, Escoubas, P, Scarzello, S et al. (2004). A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons. EMBO J 23: 1516-1525.
49. Benson, CJ, Xie, J, Wemmie, JA, Price, MP, Henss, JM, Welsh, MJ et al. (2002). Heteromultimers of DEG/ENaC subunits form H+-gated channels in mouse sensory neurons. Proc Natl Acad Sci USA 99: 2338-2343.
50. Gentleman, RC, Carey, VJ, Bates, DM, Bolstad, B, Dettling, M, Dudoit, S et al. (2004). Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5: R80.
51. Dunning, MJ, Smith, ML, Ritchie, ME and Tavaré, S (2007). beadarray: R classes and methods for Illumina bead-based data. Bioinformatics 23: 2183-2184.
52. Stacklies, W, Redestig, H, Scholz, M, Walther, D and Selbig, J (2007). pcaMethods-a bioconductor package providing PCA methods for incomplete data. Bioinformatics 23: 1164-1167.
53. Smyth, GK (2005) Limma: linear models for microarray data. Bioinformatics and Computational Biology Solutions using R and Bioconductor, 397-420.
54. Gviz: Plotting data and annotation information along genomic coordinates. (2013).