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Cited by 200Developmental Biology and Gene RegulationPlanarian Biology and ElectrostimulationCongenital heart defects research

Gene regulatory programmes of tissue regeneration

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Goldman, Joseph A., Poss, Kenneth D.·2020·Nature Reviews Genetics
DOI 10.1038/s41576-020-0239-7PMC PMC7448550
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Abstract

Regeneration is the process by which organisms replace lost or damaged tissue, and regenerative capacity can vary greatly among species, tissues and life stages. Tissue regeneration shares certain hallmarks of embryonic development, in that lineage-specific factors can be repurposed upon injury to initiate morphogenesis; however, many differences exist between regeneration and embryogenesis. Recent studies of regenerating tissues in laboratory model organisms - such as acoel worms, frogs, fish and mice - have revealed that chromatin structure, dedicated enhancers and transcriptional networks are regulated in a context-specific manner to control key gene expression programmes. A deeper mechanistic understanding of the gene regulatory networks of regeneration pathways might ultimately enable their targeted reactivation as a means to treat human injuries and degenerative diseases. In this Review, we consider the regeneration of body parts across a range of tissues and species to explore common themes and potentially exploitable elements.

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  1. [1]Poss KD Advances in understanding tissue regenerative capacity and mechanisms in animals. Nature Publishing Group 11, 710– 722 (2010). PMC3069856 20838411
  2. [2]Mokalled MH & Poss KD A Regeneration Toolkit. Developmental Cell 47, 267– 280 (2018). 30399333 PMC6373444
  3. [3]Rafii S, Butler JM & Ding B-S Angiocrine functions of organ-specific endothelial cells. Nature 529, 316– 325 (2016). 26791722 PMC4878406
  4. [4]Wells JM & Watt FM Diverse mechanisms for endogenous regeneration and repair in mammalian organs. Nature 557, 322– 328 (2018). 29769669
  5. [5]Wosczyna MN & Rando TA A Muscle Stem Cell Support Group: Coordinated Cellular Responses in Muscle Regeneration. Developmental Cell 46, 135– 143 (2018). 30016618 PMC6075730
  6. [6]Kikuchi K Primary contribution to zebrafish heart regeneration by gata4(+) cardiomyocytes. Nature 464, 601– 605 (2010). 20336144 PMC3040215
  7. [7]Wagner DE, Wang IE & Reddien PW Clonogenic neoblasts are pluripotent adult stem cells that underlie planarian regeneration. Science 332, 811– 816 (2011). 21566185 PMC3338249
  8. [8]Kragl M Cells keep a memory of their tissue origin during axolotl limb regeneration. Nature 460, 60– 65 (2009). 19571878
  9. [9]Dor Y, Brown J, Martinez OI & Melton DA Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429, 41– 46 (2004). 15129273
  10. [10]Knopf F Bone Regenerates via Dedifferentiation of Osteoblasts in the Zebrafish Fin. Developmental Cell 20, 713– 724 (2011). 21571227
  11. [11]Gomez-Salinero JM & Rafii S Endothelial cell adaptation in regeneration. Science 362, 1116– 1117 (2018). 30523098
  12. [12]Naik S, Larsen SB, Cowley CJ & Fuchs E Two to Tango: Dialog between Immunity and Stem Cells in Health and Disease. Cell 175, 908– 920 (2018). 30388451 PMC6294328
  13. [13]Stevens KR & Murry CE Human Pluripotent Stem Cell-Derived Engineered Tissues: Clinical Considerations. Cell Stem Cell 22, 294– 297 (2018). 29499147 PMC6344123
  14. [14]Lepilina A A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration. Cell 127, 607– 619 (2006). 17081981
  15. [15]Fausett BV & Goldman D A role for alpha1 tubulin-expressing Müller glia in regeneration of the injured zebrafish retina. J. Neurosci 26, 6303– 6313 (2006). 16763038 PMC6675181
  16. [16]Ransom RC Mechanoresponsive stem cells acquire neural crest fate in jaw regeneration. Nature 563, 514– 521 (2018). 30356216 PMC6481292
  17. [17]Honkoop H Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart. Elife 8, 98 (2019). PMC7000220 31868166
  18. [18]Kumar A, Gates PB & Brockes JP Positional identity of adult stem cells in salamander limb regeneration. C. R. Biol 330, 485– 490 (2007). 17631442
  19. [19]Nowoshilow S The axolotl genome and the evolution of key tissue formation regulators. Nature 554, 1– 20 (2018). 29364872
  20. [20]Blassberg RA, Garza-Garcia A, Janmohamed A, Gates PB & Brockes JP Functional convergence of signalling by GPI-anchored and anchorless forms of a salamander protein implicated in limb regeneration. Journal of Cell Science 124, 47– 56 (2011). 21118959 PMC3001407
  21. [21]Elewa A Reading and editing the Pleurodeles waltl genome reveals novel features of tetrapod regeneration. Nature Communications 8, 2286– 9 (2017). PMC5741667 29273779
  22. [22]Gerber T Single-cell analysis uncovers convergence of cell identities during axolotl limb regeneration. Science 362, (2018). PMC6669047 30262634 This study used single-cell transcriptome sequencing of connective tissue in regenerating Axolotl limbs to detect a regeneration gene signature that precedes the emergence of an embryonic-like gene expression program.
  23. [23]Aztekin C Identification of a regeneration-organizing cell in the Xenopus tail. Science 364, 653– 658 (2019). 31097661 PMC6986927 Using a time series between regenerative and non-regenerative stages in Xenopus, Aztekin et. al. uncovered a regeneration-specific gene expression signature.
  24. [24]Oulhen N Regeneration in bipinnaria larvae of the bat star Patiria miniata induces rapid and broad new gene expression. Mech. Dev 142, 10– 21 (2016). 27555501 PMC5154901
  25. [25]Storer MA Acquisition of a Unique Mesenchymal Precursor-like Blastema State Underlies Successful Adult Mammalian Digit Tip Regeneration. Developmental Cell (2019). doi: 10.1016/j.devcel.2019.12.004 31902657 · DOI
  26. [26]Olson EN Gene regulatory networks in the evolution and development of the heart. Science 313, 1922– 1927 (2006). 17008524 PMC4459601
  27. [27]Gupta V An injury-responsive gata4 program shapes the zebrafish cardiac ventricle. Curr. Biol 23, 1221– 1227 (2013). 23791730 PMC3759223
  28. [28]Schindler YL Hand2 elevates cardiomyocyte production during zebrafish heart development and regeneration. Development 141, 3112– 3122 (2014). 25038045 PMC4197543
  29. [29]Oka T, Xu J & Molkentin JD Re-employment of developmental transcription factors in adult heart disease. Semin. Cell Dev. Biol 18, 117– 131 (2007). 17161634 PMC1855184
  30. [30]Bisping E Gata4 is required for maintenance of postnatal cardiac function and protection from pressure overload-induced heart failure. Proc. Natl. Acad. Sci. U.S.A 103, 14471– 14476 (2006). 16983087 PMC1636702
  31. [31]Wong AY & Whited JL Parallels between wound healing, epimorphic regeneration and solid tumors. Development 147, dev181636 (2020). 31898582 PMC6983724
  32. [32]Catarino RR & Stark A Assessing sufficiency and necessity of enhancer activities for gene expression and the mechanisms of transcription activation. Genes & Development 32, 202– 223 (2018). 29491135 PMC5859963
  33. [33]Osterwalder M Enhancer redundancy provides phenotypic robustness in mammalian development. Nature 554, 1– 27 (2018). PMC5808607 29420474
  34. [34]Farley EK Suboptimization of developmental enhancers. Science 350, 325– 328 (2015). 26472909 PMC4970741
  35. [35]Kang J Modulation of tissue repair by regeneration enhancer elements. Nature 532, 201– 206 (2016). 27049946 PMC4844022 This paper revealed regeneration-responsive transcriptional enhancers and showed they can be adapted to deliver pro-regenerative factors.
  36. [36]Goldman JA Resolving Heart Regeneration by Replacement Histone Profiling. Developmental Cell 40, 392– 404.e5 (2017). 28245924 PMC5367476 This study used a transgenic histone-tagging approach to identify and validate many regeneration-responsive enhancer elements relevant to cardiomyocyte regeneration.
  37. [37]Pfefferli C & Jaźwińska A The careg element reveals a common regulation of regeneration in the zebrafish myocardium and fin. Nature Communications 8, 15151 (2017). PMC5418624 28466843
  38. [38]Vizcaya-Molina E Damage-responsive elements in Drosophila regeneration. Genome Research 28, 1852– 1866 (2018). 30459214 PMC6280756 This work profiled enhancers from Drosophila imaginal discs that are active during regeneration and compared them to those in embryonic development and from other regeneration models.
  39. [39]Gehrke AR Acoel genome reveals the regulatory landscape of whole-body regeneration. Science 363, eaau6173 (2019). 30872491 This manuscript describes egr1 as a pioneer transcription factor and possible master regulator required for whole body regeneration in the acoel worm, Hofstenia miamia.
  40. [40]Suzuki N Arid3a regulates nephric tubule regeneration via evolutionarily conserved regeneration signal-response enhancers. Elife 8, 455 (2019). PMC6324879 30616715
  41. [41]Ishihara H Primed histone demethylation regulates shoot regenerative competency. Nature Communications 10, 1786 (2019). PMC6467990 30992430
  42. [42]Hewitt KJ GATA Factor-Regulated Samd14 Enhancer Confers Red Blood Cell Regeneration and Survival in Severe Anemia. Developmental Cell 42, 213– 225.e4 (2017). 28787589 PMC5578808
  43. [43]Soukup AA Single-nucleotide human disease mutation inactivates a blood-regenerative GATA2 enhancer. J. Clin. Invest 129, 1180– 1192 (2019). 30620726 PMC6391105
  44. [44]Harris RE, Setiawan L, Saul J & Hariharan IK Localized epigenetic silencing of a damage-activated WNT enhancer limits regeneration in mature Drosophila imaginal discs. Elife 5, 49 (2016). PMC4786413 26840050 This manuscript describes Polycomb-mediated decommissioning of an embryonic enhancer limiting regenerative capacity in Drosophila imaginal discs.
  45. [45]Davis RL, Weintraub H & Lassar AB Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51, 987– 1000 (1987). 3690668
  46. [46]Takahashi K & Yamanaka S Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors. Cell 126, 663– 676 (2006). 16904174
  47. [47]Ivankovic M Model systems for regeneration: planarians. Development 146, dev167684 (2019). 31511248
  48. [48]Cary GA, Wolff A, Zueva O, Pattinato J & Hinman VF Analysis of sea star larval regeneration reveals conserved processes of whole-body regeneration across the metazoa. BMC Biol 17, 16– 19 (2019). 30795750 PMC6385403
  49. [49]Iwafuchi-Doi M & Zaret KS Cell fate control by pioneer transcription factors. Development 143, 1833– 1837 (2016). 27246709 PMC6514407
  50. [50]Keyes BE & Fuchs E Stem cells: Aging and transcriptional fingerprints. The Journal of Cell Biology 217, 79– 92 (2018). 29070608 PMC5748991
  51. [51]Yu Z Hoxc-Dependent Mesenchymal Niche Heterogeneity Drives Regional Hair Follicle Regeneration. Cell Stem Cell 23, 487– 500.e6 (2018). 30122476
  52. [53]Ramachandran R, Reifler A, Parent JM & Goldman D Conditional gene expression and lineage tracing of tuba1a expressing cells during zebrafish development and retina regeneration. J. Comp. Neurol 518, 4196– 4212 (2010). 20878783 PMC2948409
  53. [54]Ito K Differential reparative phenotypes between zebrafish and medaka after cardiac injury. Dev. Dyn 243, 1106– 1115 (2014). 24947076
  54. [55]Lust K & Wittbrodt J Activating the regenerative potential of Müller glia cells in a regeneration-deficient retina. Elife 7, 7028 (2018). PMC5815849 29376827
  55. [56]Gadye L Injury Activates Transient Olfactory Stem Cell States with Diverse Lineage Capacities. Cell Stem Cell 21, 775– 790.e9 (2017). 29174333 PMC5728414
  56. [57]Rocha-Martins M De novo genesis of retinal ganglion cells by targeted expression of Klf4 in vivo. Development 146, dev176586 (2019). 31405994
  57. [59]Porrello ER Transient regenerative potential of the neonatal mouse heart. Science 331, 1078– 1080 (2011). 21350179 PMC3099478
  58. [60]Porrello ER Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family. Proc. Natl. Acad. Sci. U.S.A 110, 187– 192 (2013). 23248315 PMC3538265
  59. [61]Hirose K Evidence for hormonal control of heart regenerative capacity during endothermy acquisition. Science 364, 184– 188 (2019). 30846611 PMC6541389
  60. [62]Marshall LN Stage-dependent cardiac regeneration in Xenopus is regulated by thyroid hormone availability. Proceedings of the National Academy of Sciences 116, 3614– 3623 (2019). PMC6397552 30755533
  61. [63]Patterson M Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration. Nature Publishing Group 49, 1346– 1353 (2017). PMC5736145 28783163
  62. [64]Mahmoud AI Meis1 regulates postnatal cardiomyocyte cell cycle arrest. Nature 497, 249– 253 (2013). 23594737 PMC4159712
  63. [65]Yu F-X & Guan K-L The Hippo pathway: regulators and regulations. Genes & Development 27, 355– 371 (2013). 23431053 PMC3589553
  64. [66]Xin M Hippo pathway effector Yap promotes cardiac regeneration. Proceedings of the National Academy of Sciences 110, 13839– 13844 (2013). PMC3752208 23918388
  65. [67]Leach JP Hippo pathway deficiency reverses systolic heart failure after infarction. Nature 550, 260– 264 (2017). 28976966 PMC5729743
  66. [68]Gise, von A YAP1, the nuclear target of Hippo signaling, stimulates heart growth through cardiomyocyte proliferation but not hypertrophy. Proc. Natl. Acad. Sci. U.S.A 109, 2394– 2399 (2012). 22308401 PMC3289361
  67. [69]Wang J, Liu S, Heallen T & Martin JF The Hippo pathway in the heart: pivotal roles in development, disease, and regeneration. Nat Rev Cardiol 15, 1– 684 (2018). 30111784
  68. [70]Monroe TO YAP Partially Reprograms Chromatin Accessibility to Directly Induce Adult Cardiogenesis In Vivo. Developmental Cell 48, 765– 779.e7 (2019). 30773489 PMC6435425 The combined work of Chang et al., Li et al., Sun et al. and Monroe et al. suggest a model where mechanical transduction initiates chromatin reprogramming by the combined action of Swi/Snf and YAP signaling during liver and heart regeneration.
  69. [71]Schuettengruber B & Cavalli G Recruitment of polycomb group complexes and their role in the dynamic regulation of cell fate choice. Development 136, 3531– 3542 (2009). 19820181
  70. [72]Narlikar GJ, Fan H-Y & Kingston RE Cooperation between complexes that regulate chromatin structure and transcription. Cell 108, 475– 487 (2002). 11909519
  71. [73]Lau MS Mutation of a nucleosome compaction region disrupts Polycomb-mediated axial patterning. Science 355, 1081– 1084 (2017). 28280206 PMC5503153
  72. [74]Ben-Yair R H3K27me3-mediated silencing of structural genes is required for zebrafish heart regeneration. Development 146, dev178632 (2019). 31427288 PMC6803378 This work showed that Polycomb activity can be pro-regenerative by promoting dedifferentiation through silencing sarcomeric genes in muscle.
  73. [75]Maki N, Tsonis PA & Agata K Changes in global histone modifications during dedifferentiation in newt lens regeneration. Mol. Vis 16, 1893– 1897 (2010). 21031136 PMC2956703
  74. [76]Ahmad K & Henikoff S Modulation of a transcription factor counteracts heterochromatic gene silencing in Drosophila. Cell 104, 839– 847 (2001). 11290322
  75. [77]Meshorer E Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Developmental Cell 10, 105– 116 (2006). 16399082 PMC1868458
  76. [79]Fan X Dynamic Alterations to α-Actinin Accompanying Sarcomere Disassembly and Reassembly during Cardiomyocyte Mitosis. PLoS ONE 10, e0129176 (2015). 26076379 PMC4467976
  77. [81]Dai Y-S, Cserjesi P, Markham BE & Molkentin JD The transcription factors GATA4 and dHAND physically interact to synergistically activate cardiac gene expression through a p300-dependent mechanism. J. Biol. Chem 277, 24390– 24398 (2002). 11994297
  78. [82]Samarajeewa A Transcriptional response to Wnt activation regulates the regenerative capacity of the mammalian cochlea. Development 145, dev166579– 27 (2018). 30389848 PMC6288390
  79. [83]Hariharan IK & Serras F Imaginal disc regeneration takes flight. Current Opinion in Cell Biology 48, 10– 16 (2017). 28376317 PMC5591769
  80. [84]Pengelly AR, Copur Ö, Jäckle H, Herzig A & Müller J A histone mutant reproduces the phenotype caused by loss of histone-modifying factor Polycomb. Science 339, 698– 699 (2013). 23393264
  81. [85]Quaife-Ryan GA Multicellular Transcriptional Analysis of Mammalian Heart Regeneration. Circulation 136, 1123– 1139 (2017). 28733351 PMC5598916
  82. [87]Sif S, Stukenberg PT, Kirschner MW & Kingston RE Mitotic inactivation of a human SWI/SNF chromatin remodeling complex. Genes & Development 12, 2842– 2851 (1998). 9744861 PMC317164
  83. [88]Ponnusamy M The Long Non-Coding RNA CPR Regulates Cardiomyocyte Proliferation and Cardiac Repair. Circulation 331, 1078– 44 (2019). 30832495
  84. [89]Jen H-I Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1. Elife 8, W3 (2019). PMC6504235 31033441
  85. [90]Palacios D TNF/p38α/polycomb signaling to Pax7 locus in satellite cells links inflammation to the epigenetic control of muscle regeneration. Cell Stem Cell 7, 455– 469 (2010). 20887952 PMC2951277
  86. [91]Katsuyama T & Paro R Epigenetic reprogramming during tissue regeneration. FEBS LETTERS 585, 1617– 1624 (2011). 21569771
  87. [92]Shaw T & Martin P Epigenetic reprogramming during wound healing: loss of polycomb-mediated silencing may enable upregulation of repair genes. EMBO Rep 10, 881– 886 (2009). 19575012 PMC2726669
  88. [93]Stewart S, Tsun Z-Y & Izpisua Belmonte JC A histone demethylase is necessary for regeneration in zebrafish. Proc. Natl. Acad. Sci. U.S.A 106, 19889– 19894 (2009). 19897725 PMC2785262
  89. [94]Lin B Injury Induces Endogenous Reprogramming and Dedifferentiation of Neuronal Progenitors to Multipotency. Cell Stem Cell 21, 761– 774.e5 (2017). 29174332 PMC5722700
  90. [95]Wang S Epigenetic Compensation Promotes Liver Regeneration. Developmental Cell 50, 43– 56.e6 (2019). 31231040 PMC6615735 This work showed that disruption of DNA methylation by the knockout of Uhrf1 in mice inhibits normal Polycomb function by redistributing it to compensate for silencing of transposons.
  91. [96]Mallen-St Clair J EZH2 couples pancreatic regeneration to neoplastic progression. Genes & Development 26, 439– 444 (2012). 22391448 PMC3305982
  92. [97]Chen H Polycomb protein Ezh2 regulates pancreatic beta-cell Ink4a/Arf expression and regeneration in diabetes mellitus. Genes & Development 23, 975– 985 (2009). 19390090 PMC2675862
  93. [98]Ai S Divergent Requirements for EZH1 in Heart Development Versus Regeneration. Circ Res 121, 106– 112 (2017). 28512107 PMC5527745
  94. [99]Fowler T, Sen R & Roy AL Regulation of primary response genes. Molecular Cell 44, 348– 360 (2011). 22055182 PMC3212756
  95. [100]Balamotis MA Complexity in transcription control at the activation domain-mediator interface. Sci Signal 2, ra20– ra20 (2009). 19417216 PMC2774526
  96. [101]Sun X Suppression of the SWI/SNF Component Arid1a Promotes Mammalian Regeneration. Stem Cell 18, 456– 466 (2016). PMC4826298 27044474
  97. [103]Zhu M Somatic Mutations Increase Hepatic Clonal Fitness and Regeneration in Chronic Liver Disease. Cell 177, 608– 621.e12 (2019). 30955891 PMC6519461 This study showed that heterozygous mutations in chromatin-activating complexes can foster regeneration in mammalian livers.
  98. [104]Smith E, Lin C & Shilatifard A The super elongation complex (SEC) and MLL in development and disease. Genes & Development 25, 661– 672 (2011). 21460034 PMC3070929
  99. [105]Moya IM & Halder G Hippo–YAP/TAZ signalling in organ regeneration and regenerative medicine. Nat Rev Mol Cell Biol 20, 1– 16 (2019). 30546055
  100. [106]Benham-Pyle BW, Pruitt BL & Nelson WJ Cell adhesion. Mechanical strain induces E-cadherin-dependent Yap1 and β-catenin activation to drive cell cycle entry. Science 348, 1024– 1027 (2015). 26023140 PMC4572847
  101. [107]Cao J Tension Creates an Endoreplication Wavefront that Leads Regeneration of Epicardial Tissue. Developmental Cell 42, 600– 615.e4 (2017). 28950101 PMC5645043
  102. [108]Chang L The SWI/SNF complex is a mechanoregulated inhibitor of YAP and TAZ. Nature 563, 265– 269 (2018). 30401838 PMC7612964
  103. [109]Tanaka EM The Molecular and Cellular Choreography of Appendage Regeneration. Cell 165, 1598– 1608 (2016). 27315477
  104. [110]Wehner D & Weidinger G Signaling networks organizing regenerative growth of the zebrafish fin. Trends Genet. 31, 336– 343 (2015). 25929514
  105. [111]Hancock ML Insulin Receptor Associates with Promoters Genome-wide and Regulates Gene Expression. Cell 177, 722– 736.e22 (2019). 30955890 PMC6478446
  106. [112]Apel PJ Effect of locally delivered IGF-1 on nerve regeneration during aging: an experimental study in rats. Muscle Nerve 41, 335– 341 (2010). 19802878 PMC3045758
  107. [113]Barton ER, Morris L, Musaro A, Rosenthal N & Sweeney HL Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice. The Journal of Cell Biology 157, 137– 148 (2002). 11927606 PMC2173262
  108. [114]Chablais F & Jaźwińska A IGF signaling between blastema and wound epidermis is required for fin regeneration. Development 137, 871– 879 (2010). 20179093
  109. [115]Choi W-Y In vivo monitoring of cardiomyocyte proliferation to identify chemical modifiers of heart regeneration. Development 140, 660– 666 (2013). 23293297 PMC3561784
  110. [116]Desbois-Mouthon C Hepatocyte proliferation during liver regeneration is impaired in mice with liver-specific IGF-1R knockout. FASEB J. 20, 773– 775 (2006). 16484330
  111. [117]Kopp F & Mendell JT Functional Classification and Experimental Dissection of Long Noncoding RNAs. Cell 172, 393– 407 (2018). 29373828 PMC5978744
  112. [118]Canzio D Antisense lncRNA Transcription Mediates DNA Demethylation to Drive Stochastic Protocadherin α Promoter Choice. Cell 177, 639– 653.e15 (2019). 30955885 PMC6823843
  113. [119]Swarr DT The long noncoding RNA Falcor regulates Foxa2 expression to maintain lung epithelial homeostasis and promote regeneration. Genes & Development (2019). doi: 10.1101/gad.320523.118 PMC6546060 30923168 · DOI
  114. [120]Shim S, Kwan KY, Li M, Lefebvre V & Sestan N Cis-regulatory control of corticospinal system development and evolution. Nature 486, 74– 79 (2012). 22678282 PMC3375921
  115. [121]Perry RB-T, Hezroni H, Goldrich MJ & Ulitsky I Regulation of Neuroregeneration by Long Noncoding RNAs. Molecular Cell 72, 553– 567.e5 (2018). 30401432 PMC6542662
  116. [122]Lin X Long non-coding RNAs regulate Wnt signaling during feather regeneration. Development 145, dev162388 (2018). 30327322
  117. [123]Boos F Mitochondrial protein-induced stress triggers a global adaptive transcriptional programme. Nature Cell Biology 21, 442– 451 (2019). 30886345
  118. [124]Eming SA, Wynn TA & Martin P Inflammation and metabolism in tissue repair and regeneration. Science 356, 1026– 1030 (2017). 28596335
  119. [125]Guo A E-C coupling structural protein junctophilin-2 encodes a stress-adaptive transcription regulator. Science 362, (2018). PMC6336677 30409805
  120. [126]Jiang H Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell 137, 1343– 1355 (2009). 19563763 PMC2753793
  121. [127]Mundorf J, Donohoe CD, McClure CD, Southall TD & Uhlirova M Ets21c Governs Tissue Renewal, Stress Tolerance, and Aging in the Drosophila Intestine. Cell Rep 27, 3019– 3033.e5 (2019). 31167145 PMC6581828
  122. [128]Jessen KR, Mirsky R & Arthur-Farraj P The Role of Cell Plasticity in Tissue Repair: Adaptive Cellular Reprogramming. Developmental Cell 34, 613– 620 (2015). 26418293
  123. [130]Arthur-Farraj PJ c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration. Neuron 75, 633– 647 (2012). 22920255 PMC3657176
  124. [131]Papp B & Plath K Epigenetics of Reprogramming to Induced Pluripotency. Cell 152, 1324– 1343 (2013). 23498940 PMC3602907
  125. [132]Schuster KJ & Smith-Bolton RK Taranis Protects Regenerating Tissue from Fate Changes Induced by the Wound Response in Drosophila. Developmental Cell 34, 119– 128 (2015). 26096735
  126. [133]Worley MI, Alexander LA & Hariharan IK CtBP impedes JNK- and Upd/STAT-driven cell fate misspecifications in regenerating Drosophila imaginal discs. Elife 7, 487 (2018). PMC5823544 29372681
  127. [134]Hyman AA, Weber CA & Jülicher F Liquid-Liquid Phase Separation in Biology. Annu. Rev. Cell Dev. Biol 30, 39– 58 (2014). 25288112
  128. [135]Hnisz D, Shrinivas K, Young RA, Chakraborty AK & Sharp PA A Phase Separation Model for Transcriptional Control. Cell 169, 13– 23 (2017). 28340338 PMC5432200
  129. [136]Gehani SS Polycomb group protein displacement and gene activation through MSK-dependent H3K27me3S28 phosphorylation. Molecular Cell 39, 886– 900 (2010). 20864036
  130. [137]Lau PNI & Cheung P Histone code pathway involving H3 S28 phosphorylation and K27 acetylation activates transcription and antagonizes polycomb silencing. Proc. Natl. Acad. Sci. U.S.A 108, 2801– 2806 (2011). 21282660 PMC3041124
  131. [138]Cai D Phase separation of YAP reorganizes genome topology for long-term YAP target gene expression. Nature Cell Biology 21, 1578– 1589 (2019). 31792379 PMC8259329
  132. [139]Wu C-C Spatially Resolved Genome-wide Transcriptional Profiling Identifies BMP Signaling as Essential Regulator of Zebrafish Cardiomyocyte Regeneration. Developmental Cell 36, 36– 49 (2016). 26748692
  133. [140]Rodriques SG Slide-seq: A scalable technology for measuring genome-wide expression at high spatial resolution. Science 363, 1463– 1467 (2019). 30923225 PMC6927209
  134. [141]Eng C-HL Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH. Nature 568, 235– 239 (2019). 30911168 PMC6544023
  135. [142]Rhee H-W Proteomic mapping of mitochondria in living cells via spatially restricted enzymatic tagging. Science 339, 1328– 1331 (2013). 23371551 PMC3916822
  136. [143]Xie S, Duan J, Li B, Zhou P & Hon GC Multiplexed Engineering and Analysis of Combinatorial Enhancer Activity in Single Cells. Molecular Cell 66, 285– 299.e5 (2017). 28416141
  137. [145]Hainer SJ, Bošković A, McCannell KN, Rando OJ & Fazzio TG Profiling of Pluripotency Factors in Single Cells and Early Embryos. Cell 177, 1319– 1329.e11 (2019). 30955888 PMC6525046
  138. [148]van Heesch S The Translational Landscape of the Human Heart. Cell 178, 242– 260.e29 (2019). 31155234
  139. [149]Anguela XM & High KA Entering the Modern Era of Gene Therapy. Annu. Rev. Med 70, 273– 288 (2019). 30477394
  140. [151]Chicoine LG Plasmapheresis Eliminates the Negative Impact of AAV Antibodies on Microdystrophin Gene Expression Following Vascular Delivery. Molecular Therapy 22, 338– 347 (2016). PMC3916040 24196577
  141. [152]Recino A Immunosuppression overcomes insulin- and vector-specific immune responses that limit efficacy of AAV2/8-mediated insulin gene therapy in NOD mice. Gene Ther. 26, 40– 56 (2019). 30514969 PMC6514884
  142. [154]Liao H-K In Vivo Target Gene Activation via CRISPR/Cas9-Mediated Trans-epigenetic Modulation. Cell 171, 1495– 1507.e15 (2017). 29224783 PMC5732045
  143. [155]Davidsson M A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism. Proceedings of the National Academy of Sciences 116, 27053– 27062 (2019). PMC6936499 31818949
  144. [156]Bracken AP, Brien GL & Verrijzer CP Dangerous liaisons: interplay between SWI/SNF, NuRD, and Polycomb in chromatin regulation and cancer. Genes & Development 33, 936– 959 (2019). 31123059 PMC6672049
  145. [157]Venable JH Constant cell populations in normal, testosterone-deprived and testosterone-stimulated levator ani muscles. Am. J. Anat 119, 263– 270 (1966). 5970437
  146. [159]Carr MJ Mesenchymal Precursor Cells in Adult Nerves Contribute to Mammalian Tissue Repair and Regeneration. Cell Stem Cell 24, 240– 256.e9 (2019). 30503141
  147. [160]Mahmoud AI Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration. Developmental Cell 34, 387– 399 (2015). 26256209 PMC4550513
  148. [161]Kumar A, Godwin JW, Gates PB, Garza-Garcia AA & Brockes JP Molecular basis for the nerve dependence of limb regeneration in an adult vertebrate. Science 318, 772– 777 (2007). 17975060 PMC2696928
  149. [162]THORNTON CS The effect of apical cap removal on limb regeneration in Amblystoma larvae. J. Exp. Zool 134, 357– 381 (1957). 13428959
  150. [164]Siebert S Stem cell differentiation trajectories in Hydraresolved at single-cell resolution. Science 365, eaav9314– 10 (2019). 31346039 PMC7104783
  151. [165]Ayyaz A Single-cell transcriptomes of the regenerating intestine reveal a revival stem cell. Nature 569, 121– 125 (2019). 31019301
  152. [166]Matsumoto T, Wakefield L, Tarlow BD & Grompe M In Vivo Lineage Tracing of Polyploid Hepatocytes Reveals Extensive Proliferation during Liver Regeneration. Cell Stem Cell 26, 34– 47.e3 (2020). 31866222 PMC7204404
  153. [167]González-Rosa JM Myocardial Polyploidization Creates a Barrier to Heart Regeneration in Zebrafish. Developmental Cell 44, 433– 446.e7 (2018). 29486195 PMC5830170
  154. [168]Lucchetta EM & Ohlstein B Amitosis of Polyploid Cells Regenerates Functional Stem Cells in the Drosophila Intestine. Cell Stem Cell 20, 609– 620.e6 (2017). 28343984 PMC5419863

Cited by

Sorted by citations

Authors
Goldman, J. A., & Poss, K. D.
Affiliations
  • The Ohio State University (US)
  • Duke University (US)
Corresponding author
  • Goldman, Joseph A.
  • Poss, Kenneth D.
ORCID
Venue
Nature Reviews Genetics
Publisher
Springer Science and Business Media LLC
Published
2020-06-05
Volume
21
Issue
9
Pages
511-525
ISSN
  • 1471-0056 (ISSN-L)
  • 1471-0064
DOI
10.1038/s41576-020-0239-7
PMC
PMC7448550
OpenAlex
W3033392434
Cited by
200
References
14
Citations by year
2026: 27 · 2025: 34 · 2024: 41 · 2023: 42 · 2022: 29 · 2021: 19 · 2020: 7 · 2019: 1
FWCI
2.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Reviews Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R01HL136182, R35HL150713)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR076342)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Planarian Biology and Electrostimulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
Keywords
tissue regeneration, gene regulatory networks, chromatin structure, enhancers, transcriptional regulatory networks, embryonic development, regenerative capacity, degenerative diseases, cardiac regeneration, nervous system regeneration, regenerative medicine
MeSH terms
Animals, Humans, Regeneration, Gene Regulatory Networks

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