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Application of Optogenetics for Muscle Cells and Stem Cells

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Optogenetics

Abstract

This chapter describes the current progress of basic research, and potential therapeutic applications primarily focused on the optical manipulation of muscle cells and neural stem cells using microbial rhodopsin as a light-sensitive molecule. Since the contractions of skeletal, cardiac, and smooth muscle cells are mainly regulated through their membrane potential, several studies have been demonstrated to up- or downregulate the muscle contraction directly or indirectly using optogenetic actuators or silencers with defined stimulation patterns and intensities. Light-dependent oscillation of membrane potential also facilitates the maturation of myocytes with the development of T tubules and sarcomere structures, tandem arrays of minimum contractile units consists of contractile proteins and cytoskeletal proteins. Optogenetics has been applied to various stem cells and multipotent/pluripotent cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) to generate light-sensitive neurons and to facilitate neuroscience. The chronic optical stimulation of the channelrhodopsin-expressing neural stem cells facilitates their neural differentiation. There are potential therapeutic applications of optogenetics in cardiac pacemaking, muscle regeneration/maintenance, locomotion recovery for the treatment of muscle paralysis due to motor neuron diseases such as amyotrophic lateral sclerosis (ALS). Optogenetics would also facilitate maturation, network integration of grafted neurons, and improve the microenvironment around them when applied to stem cells.

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Abbreviations

ALS:

Amyotrophic lateral sclerosis

DA:

Dopaminergic

EFS:

Electrical field stimulation

ESC:

Embryonic stem cell

fMRI:

Functional magnetic resonance imaging

iPSC:

Induced pluripotent stem cell

NSC:

Neural stem cell

OS:

Optical stimulation

SFO:

Step-function opsin

References

  • Abilez OJ, Wong J, Prakash R et al (2011) Multiscale computational models for optogenetic control of cardiac function. Biophys J 101:1326–1334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adamantidis A, Arber S, Bains JS et al (2015) Optogenetics: 10 years after ChR2 in neurons--views from the community. Nat Neurosci 18:1202–1212

    Article  CAS  PubMed  Google Scholar 

  • Anderson MA, Burda JE, Ren Y et al (2016) Astrocyte scar formation aids central nervous system axon regeneration. Nature 532:195–200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aravanis AM, Wang LP, Zhang F et al (2007) An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology. J Neural Eng 4:S143–S156

    Article  PubMed  Google Scholar 

  • Arrenberg AB, Stainier DY, Baier H et al (2010) Optogenetic control of cardiac function. Science 330:971–974

    Article  CAS  PubMed  Google Scholar 

  • Asano T, Ishizuka T, Yawo H (2012) Optically controlled contraction of photosensitive skeletal muscle cells. Biotechnol Bioeng 109:199–204

    Article  CAS  PubMed  Google Scholar 

  • Asano T, Ishizuka T, Morishima K et al (2015) Optogenetic induction of contractile ability in immature C2C12 myotubes. Sci Rep 5:8317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Asano T, Igarashi H, Ishizuka T et al (2018) Organelle optogenetics: direct manipulation of intracellular Ca2+ dynamics by light. Front Neurosci 12:561

    Article  PubMed  PubMed Central  Google Scholar 

  • Avaliani N, Sørensen AT, Ledri M et al (2014) Optogenetics reveal delayed afferent synaptogenesis on grafted human-induced pluripotent stem cell-derived neural progenitors. Stem Cells 32:3088–3098

    Article  CAS  PubMed  Google Scholar 

  • Berndt A, Yizhar O, Gunaydin LA et al (2009) Bi-stable neural state switches. Nat Neurosci 12:229–234

    Article  CAS  PubMed  Google Scholar 

  • Blasiak A, Nag S, Yang IH (2018) Subcellular optogenetic stimulation platform for studying activity-dependent axon myelination in vitro. Methods Mol Biol 1791:207–224

    Article  CAS  PubMed  Google Scholar 

  • Boyle PM, Karathanos TV, Trayanova NA (2018) Cardiac optogenetics: 2018. JACC Clin Electrophysiol 4:155–167

    Article  PubMed  PubMed Central  Google Scholar 

  • Bruegmann T, Malan D, Hesse M et al (2010) Optogenetic control of heart muscle in vitro and in vivo. Nat Methods 7:897–900

    Article  CAS  PubMed  Google Scholar 

  • Bruegmann T, van Bremen T, Vogt CC et al (2015) Optogenetic control of contractile function in skeletal muscle. Nat Commun 6:7153

    Article  CAS  PubMed  Google Scholar 

  • Bryson JB, Barcellos Machado C, Crossley M et al (2014) Optical control of muscle function by transplantation of stem cell-derived motor neurons in mice. Science 344:94–97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Byers B, Lee HJ, Liu J et al (2015) Direct in vivo assessment of human stem cell graft-host neural circuits. NeuroImage 114:328–337

    Article  PubMed  Google Scholar 

  • Daadi MM, Klausner JQ, Bajar B et al (2016) Optogenetic stimulation of neural grafts enhances neurotransmission and downregulates the inflammatory response in experimental stroke model. Cell Transplant 25:1371–1380

    Article  PubMed  Google Scholar 

  • D’Ascenzo M, Piacentini R, Casalbore P et al (2006) Role of L-type Ca2+ channels in neural stem/progenitor cell differentiation. Eur J Neurosci 23:935–944

    Article  PubMed  Google Scholar 

  • Deisseroth K (2015) Optogenetics: 10 years of microbial opsins in neuroscience. Nat Neurosci 18:1213–1225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deisseroth K, Hegemann P (2017) The form and function of channelrhodopsin. Science 357:eaan5544

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ding H, Lu L, Shi Z et al (2018) Microscale optoelectronic infrared-to-visible upconversion devices and their use as injectable light sources. Proc Natl Acad Sci U S A 115:6632–6637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Funken M, Malan D, Sasse P et al (2019) Optogenetic hyperpolarization of cardiomyocytes terminates ventricular arrhythmia. Front Physiol 10:498

    Article  PubMed  PubMed Central  Google Scholar 

  • Garita-Hernandez M, Guibbal L, Toualbi L et al (2018) Optogenetic light sensors in human retinal organoids. Front Neurosci 12:789

    Article  PubMed  PubMed Central  Google Scholar 

  • Garita-Hernandez M, Lampič M, Chaffiol A et al (2019) Restoration of visual function by transplantation of optogenetically engineered photoreceptors. Nat Commun 10:4524

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gibson EM, Purger D, Mount CW et al (2014) Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain. Science 344:1252304

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gordon K, Del Medico A, Sander I et al (2019) Gene therapies in ophthalmic disease. Nat Rev Drug Discov 18:415–416

    Article  CAS  PubMed  Google Scholar 

  • Hososhima S, Sakai S, Ishizuka T et al (2015) Kinetic evaluation of photosensitivity in bi-stable variants of chimeric channelrhodopsins. PLoS One 10:e0119558

    Google Scholar 

  • Igarashi H, Ikeda K, Onimaru H et al (2018) Targeted expression of step-function opsins in transgenic rats for optogenetic studies. Sci Rep 8:5435

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Iino M (2010) Spatiotemporal dynamics of Ca2+ signaling and its physiological roles. Proc Jpn Acad Ser B Phys Biol Sci 86:244–256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jacobson M (1991) Developmental neurobiology, 3rd edn. Plenum Press, New York

    Book  Google Scholar 

  • Jia Z, Valiunas V, Lu Z et al (2011) Stimulating cardiac muscle by light: cardiac optogenetics by cell delivery. Circ Arrhythm Electrophysiol 4:753–760

    Article  PubMed  PubMed Central  Google Scholar 

  • Jung K, Park JH, Kim SY et al (2019) Optogenetic stimulation promotes Schwann cell proliferation, differentiation, and myelination in vitro. Sci Rep 9:3487

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Karra D, Dahm R (2010) Transfection techniques for neuronal cells. J Neurosci 30:6171–6177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kikuchi T, Morizane A, Doi D et al (2017) Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model. Nature 548:592–596

    Article  CAS  PubMed  Google Scholar 

  • Köhidi T, Jády AG, Markó K et al (2017) Differentiation-dependent motility-responses of developing neural progenitors to optogenetic stimulation. Front Cell Neurosci 11:401

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee HU, Blasiak A, Agrawal DR et al (2017) Subcellular electrical stimulation of neurons enhances the myelination of axons by oligodendrocytes. PLoS One 12:e0179642

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lisman J, Spruston N (2005) Postsynaptic depolarization requirements for LTP and LTD: a critique of spike timing-dependent plasticity. Nat Neurosci 8:839–841

    Article  CAS  PubMed  Google Scholar 

  • Llewellyn ME, Thompson KR, Deisseroth K et al (2010) Orderly recruitment of motor units under optical control in vivo. Nat Med 16:1161–1165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Magown P, Shettar B, Zhang Y et al (2015) Direct optical activation of skeletal muscle fibres efficiently controls muscle contraction and attenuates denervation atrophy. Nat Commun 6:8506

    Article  CAS  PubMed  Google Scholar 

  • Mirzapour Delavar H, Karamzadeh A, Pahlavanneshan S (2016) Shining light on the sprout of life: optogenetics applications in stem cell research and therapy. J Membr Biol 249:215–220

    Article  CAS  PubMed  Google Scholar 

  • Miyashita T, Shao Y, Chung J et al (2013) Long-term channelrhodopsin-2 (ChR2) expression can induce abnormal axonal morphology and targeting in cerebral cortex. Front Neural Circuits 7:8

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nagel G, Szellas T, Huhn W et al (2003) Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proc Natl Acad Sci U S A 100:13940–13945

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Numa S, Tanabe T, Takeshima H et al (1990) Molecular insights into excitation-contraction coupling. Cold Spring Harb Symp Quant Biol 55:1–7

    Article  CAS  PubMed  Google Scholar 

  • Nussinovitch U, Gepstein L (2015) Optogenetics for in vivo cardiac pacing and resynchronization therapies. Nat Biotechnol 33:750–754

    Article  CAS  PubMed  Google Scholar 

  • Nussinovitch U, Shinnawi R, Gepstein L (2014) Modulation of cardiac tissue electrophysiological properties with light-sensitive proteins. Cardiovasc Res 102:176–187

    Article  CAS  PubMed  Google Scholar 

  • Park JH, Hong JK, Jang JY et al (2017) Optogenetic modulation of urinary bladder contraction for lower urinary tract dysfunction. Sci Rep 7:40872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Piña-Crespo JC, Talantova M, Cho EG et al (2012) High-frequency hippocampal oscillations activated by optogenetic stimulation of transplanted human ESC-derived neurons. J Neurosci 32:15837–15842

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Prakriya M, Lewis RS (2015) Store-operated calcium channels. Physiol Rev 95:1383–1436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raman R, Cvetkovic C, Uzel SG et al (2016) Optogenetic skeletal muscle-powered adaptive biological machines. Proc Natl Acad Sci U S A 113:3497–3502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ricotti L, Menciassi A (2012) Bio-hybrid muscle cell-based actuators. Biomed Microdevices 14:987–998

    Article  PubMed  Google Scholar 

  • Rorsman NJG, Ta CM, Garnett H et al (2018) Defining the ionic mechanisms of optogenetic control of vascular tone by channelrhodopsin-2. Br J Pharmacol 175:2028–2045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rost BR, Schneider-Warme F, Schmitz D et al (2017) Optogenetic tools for subcellular applications in neuroscience. Neuron 96:572–603

    Article  CAS  PubMed  Google Scholar 

  • Sakar MS, Neal D, Boudou T et al (2012) Formation and optogenetic control of engineered 3D skeletal muscle bioactuators. Lab Chip 12:4976–4985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schneider F, Grimm C, Hegemann P (2015) Biophysics of channelrhodopsin. Annu Rev Biophys 44:167–186

    Article  CAS  PubMed  Google Scholar 

  • Sidor MM, Davidson TJ, Tye KM et al (2015) In vivo optogenetic stimulation of the rodent central nervous system. J Vis Exp 95:e51483

    Google Scholar 

  • Sineshchekov OA, Li H, Govorunova EG et al (2016) Photochemical reaction cycle transitions during anion channelrhodopsin gating. Proc Natl Acad Sci U S A 113:E1993–E2000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steinbeck JA, Choi SJ, Mrejeru A et al (2015) Optogenetics enables functional analysis of human embryonic stem cell-derived grafts in a Parkinson’s disease model. Nat Biotechnol 33:204–209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stroh A, Tsai HC, Wang LP et al (2011) Tracking stem cell differentiation in the setting of automated optogenetic stimulation. Stem Cells 29:78–88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takahashi J (2019) Preparing for first human trial of induced pluripotent stem cell-derived cells for Parkinson’s disease: an interview with Jun Takahashi. Regen Med 14:93–95

    Article  CAS  PubMed  Google Scholar 

  • Teh DB, Ishizuka T, Yawo H (2014) Regulation of later neurogenic stages of adult-derived neural stem/progenitor cells by L-type Ca2+ channels. Develop Growth Differ 56:583–594

    Article  CAS  Google Scholar 

  • Teh DBL, Prasad A, Jiang W et al (2020) Driving neurogenesis in neural stem cells with high sensitivity optogenetics. Neuromolecular Med 22:139–149

    Google Scholar 

  • Toettcher JE, Voigt CA, Weiner OD et al (2011) The promise of optogenetics in cell biology: interrogating molecular circuits in space and time. Nat Methods 8:35–38

    Article  CAS  PubMed  Google Scholar 

  • Tønnesen J, Parish CL, Sørensen AT et al (2011) Functional integration of grafted neural stem cell-derived dopaminergic neurons monitored by optogenetics in an in vitro Parkinson model. PLoS One 6:e17560

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vogt CC, Bruegmann T, Malan D et al (2015) Systemic gene transfer enables optogenetic pacing of mouse hearts. Cardiovasc Res 106:338–343

    Article  CAS  PubMed  Google Scholar 

  • Wang S, Du L, Peng GH (2019) Optogenetic stimulation inhibits the self-renewal of mouse embryonic stem cells. Cell Biosci 9:73

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Weick JP, Johnson MA, Skroch SP et al (2010) Functional control of transplantable human ESC-derived neurons via optogenetic targeting. Stem Cells 28:2008–2016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woodard LE, Wilson MH (2015) piggyBac-ing models and new therapeutic strategies. Trends Biotechnol 33:525–533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu Y, Li SS, Jin X et al (2015) Optogenetic approach for functional assays of the cardiovascular system by light activation of the vascular smooth muscle. Vasc Pharmacol 71:192–200

    Article  CAS  Google Scholar 

  • Yawo H, Asano T, Sakai S et al (2013) Optogenetic manipulation of neural and non-neural functions. Develop Growth Differ 55:474–490

    Google Scholar 

  • Zhang YP, Holbro N, Oertner TG (2008) Optical induction of plasticity at single synapses reveals input-specific accumulation of αCaMKII. Proc Natl Acad Sci U S A 105:12039–12044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao ML, Chen SJ, Li XH et al (2018) Optical depolarization of DCX-expressing cells promoted cognitive recovery and maturation of newborn neurons via the Wnt/β-catenin pathway. J Alzheimers Dis 63:303–318

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a JSPS (Japan Society for the Promotion of Science) Grant-in-Aid for Scientific Research (17KK0164 and 19K12777 to TA), a National University of Singapore Start-up Grant (R-183-000-413-733 and R-185-000-363-733 to DT), Grants-in-Aid for Scientific Research (KAKENHI) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan (15H01413, 25250001 and 15K15025 to HY), a Strategic International Collaborative Research Program (SICORP) from Japan Science and Technology Agency (JST) to HY as well as Research Foundation for Opto-Science and Technology to HY.

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Correspondence to Hiromu Yawo .

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Asano, T., Teh, D.B.L., Yawo, H. (2021). Application of Optogenetics for Muscle Cells and Stem Cells. In: Yawo, H., Kandori, H., Koizumi, A., Kageyama, R. (eds) Optogenetics. Advances in Experimental Medicine and Biology, vol 1293. Springer, Singapore. https://doi.org/10.1007/978-981-15-8763-4_23

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