1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Genetics
  4. Volume 57, 2023
  5. Article

Annual Review of Genetics

Volume 57, 2023

Induced Pluripotent Stem Cells in Disease Biology and the Evidence for Their In Vitro Utility

Abstract

Many human phenotypes are impossible to recapitulate in model organisms or immortalized human cell lines. Induced pluripotent stem cells (iPSCs) offer a way to study disease mechanisms in a variety of differentiated cell types while circumventing ethical and practical issues associated with finite tissue sources and postmortem states. Here, we discuss the broad utility of iPSCs in genetic medicine and describe how they are being used to study musculoskeletal, pulmonary, neurologic, and cardiac phenotypes. We summarize the particular challenges presented by each organ system and describe how iPSC models are being used to address them. Finally, we discuss emerging iPSC-derived organoid models and the potential value that they can bring to studies of human disease.

Keyword(s): gene regulation, genetics, human disease, induced pluripotent stem cells, organoids
Loading

Article metrics loading...

/content/journals/10.1146/annurev-genet-022123-090319
2023-11-27
2024-04-27
Loading full text...

Full text loading...

/deliver/fulltext/genet/57/1/annurev-genet-022123-090319.html?itemId=/content/journals/10.1146/annurev-genet-022123-090319&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Aalders J, Leger L, Van der Meeren L, Van den Vreken N, Skirtach AG et al. 2020. Effects of fibrillin mutations on the behavior of heart muscle cells in Marfan syndrome. Sci. Rep. 10:116756
     [Google Scholar]
  2. 2.
    Alysandratos KD, Russo SJ, Petcherski A, Taddeo EP, Acin-Perez R et al. 2021. Patient-specific iPSCs carrying an SFTPC mutation reveal the intrinsic alveolar epithelial dysfunction at the inception of interstitial lung disease. Cell Rep. 36:9109636
     [Google Scholar]
  3. 3.
    Badu-Mensah A, Guo X, McAleer CW, Rumsey JW, Hickman JJ. 2020. Functional skeletal muscle model derived from SOD1-mutant ALS patient iPSCs recapitulates hallmarks of disease progression. Sci. Rep. 10:114302
     [Google Scholar]
  4. 4.
    Barruet E, Morales BM, Cain CJ, Ton AN, Wentworth KL et al. 2018. NF-κB/MAPK activation underlies ACVR1-mediated inflammation in human heterotopic ossification. JCI Insight 3:22e122958
     [Google Scholar]
  5. 5.
    Barruet E, Morales BM, Lwin W, White MP, Theodoris CV et al. 2016. The ACVR1 R206H mutation found in fibrodysplasia ossificans progressiva increases human induced pluripotent stem cell-derived endothelial cell formation and collagen production through BMP-mediated SMAD1/5/8 signaling. Stem. Cell Res. Ther. 7:1115
     [Google Scholar]
  6. 6.
    Bell S, Hettige NC, Silveira H, Peng H, Wu H et al. 2019. Differentiation of human induced pluripotent stem cells (iPSCs) into an effective model of forebrain neural progenitor cells and mature neurons. Bio Protoc. 9:5e3188
     [Google Scholar]
  7. 7.
    Bertero A, Fields PA, Ramani V, Bonora G, Yardimci GG et al. 2019. Dynamics of genome reorganization during human cardiogenesis reveal an RBM20-dependent splicing factory. Nat. Commun. 10:11538
     [Google Scholar]
  8. 8.
    Bian S, Repic M, Guo Z, Kavirayani A, Burkard T et al. 2018. Genetically engineered cerebral organoids model brain tumor formation. Nat. Methods 15:8631–39
     [Google Scholar]
  9. 9.
    Briganti F, Sun H, Wei W, Wu J, Zhu C et al. 2020. iPSC modeling of RBM20-deficient DCM identifies upregulation of RBM20 as a therapeutic strategy. Cell Rep. 32:10108117
     [Google Scholar]
  10. 10.
    Buniello A, MacArthur JAL, Cerezo M, Harris LW, Hayhurst J et al. 2019. The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Res. 47:D1D1005–12
     [Google Scholar]
  11. 11.
    Burke EE, Chenoweth JG, Shin JH, Collado-Torres L, Kim SK et al. 2020. Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs. Nat. Commun. 11:1462
     [Google Scholar]
  12. 12.
    Bustamante-Marin XM, Yin W-N, Sears PR, Werner ME, Brotslaw EJ et al. 2019. Lack of GAS2L2 causes PCD by impairing cilia orientation and mucociliary clearance. Am. J. Hum. Genet. 104:2229–45
     [Google Scholar]
  13. 13.
    Cartier N, Hacein-Bey-Abina S, Bartholomae CC, Veres G, Schmidt M et al. 2009. Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science 326:5954818–23
     [Google Scholar]
  14. 14.
    Castro-Vinuelas R, Sanjurjo-Rodriguez C, Pineiro-Ramil M, Hermida-Gomez T, Rodriguez-Fernandez S et al. 2020. Generation and characterization of human induced pluripotent stem cells (iPSCs) from hand osteoarthritis patient-derived fibroblasts. Sci. Rep. 10:14272
     [Google Scholar]
  15. 15.
    Cavazzana M, Bushman FD, Miccio A, André-Schmutz I, Six E. 2019. Gene therapy targeting haematopoietic stem cells for inherited diseases: progress and challenges. Nat. Rev. Drug Discov. 18:6447–62
     [Google Scholar]
  16. 16.
    Chen HJ, Poran A, Unni AM, Huang SX, Elemento O et al. 2019. Generation of pulmonary neuroendocrine cells and SCLC-like tumors from human embryonic stem cells. J. Exp. Med. 216:3674–87
     [Google Scholar]
  17. 17.
    Chen Y-W, Huang SX, de Carvalho ALRT, Ho S-H, Islam MN et al. 2017. A three-dimensional model of human lung development and disease from pluripotent stem cells. Nat. Cell Biol. 19:5542–49
     [Google Scholar]
  18. 18.
    Cohn R, Thakar K, Lowe A, Ladha FA, Pettinato AM et al. 2019. A contraction stress model of hypertrophic cardiomyopathy due to sarcomere mutations. Stem Cell Rep. 12:171–83
     [Google Scholar]
  19. 19.
    Csobonyeiova M, Polak S, Danisovic L. 2020. Recent overview of the use of iPSCs Huntington's disease modeling and therapy. Int. J. Mol. Sci. 21:62239
     [Google Scholar]
  20. 20.
    Cuomo ASE, Seaton DD, McCarthy DJ, Martinez I, Bonder MJ et al. 2020. Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression. Nat. Commun. 11:1810
     [Google Scholar]
  21. 21.
    Duangchan T, Tawonsawatruk T, Angsanuntsukh C, Trachoo O, Hongeng S et al. 2021. Amelioration of osteogenesis in iPSC-derived mesenchymal stem cells from osteogenesis imperfecta patients by endoplasmic reticulum stress inhibitor. Life Sci. 278:119628
     [Google Scholar]
  22. 22.
    Elorbany R, Popp JM, Rhodes K, Strober BJ, Barr K et al. 2022. Single-cell sequencing reveals lineage-specific dynamic genetic regulation of gene expression during human cardiomyocyte differentiation. PLOS Genet. 18:1e1009666
     [Google Scholar]
  23. 23.
    Firth AL, Menon T, Parker GS, Qualls SJ, Lewis BM et al. 2015. Functional gene correction for cystic fibrosis in lung epithelial cells generated from patient iPSCs. Cell Rep. 12:91385–90
     [Google Scholar]
  24. 24.
    Friedman CE, Nguyen Q, Lukowski SW, Helfer A, Chiu HS et al. 2018. Single-cell transcriptomic analysis of cardiac differentiation from human PSCs reveals HOPX-dependent cardiomyocyte maturation. Cell Stem Cell 23:4586–98.e8
     [Google Scholar]
  25. 25.
    Gao Y, Pu J. 2021. Differentiation and application of human pluripotent stem cells derived cardiovascular cells for treatment of heart diseases: promises and challenges. Front. Cell Dev. Biol. 9:658088
     [Google Scholar]
  26. 26.
    Granata A, Serrano F, Bernard WG, McNamara M, Low L et al. 2017. An iPSC-derived vascular model of Marfan syndrome identifies key mediators of smooth muscle cell death. Nat. Genet. 49:197–109
     [Google Scholar]
  27. 27.
    GTEx Consort. 2020. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science 369:65091318–30
     [Google Scholar]
  28. 28.
    Han X, Chen H, Huang D, Chen H, Fei L et al. 2018. Mapping human pluripotent stem cell differentiation pathways using high throughput single-cell RNA-sequencing. Genome Biol. 19:147
     [Google Scholar]
  29. 29.
    Hawkins FJ, Suzuki S, Beermann ML, Barilla C, Wang R et al. 2021. Derivation of airway basal stem cells from human pluripotent stem cells. Cell Stem Cell 28:179–95.e8
     [Google Scholar]
  30. 30.
    High KA, Roncarolo MG. 2019. Gene therapy. N. Engl. J. Med. 381:5455–64
     [Google Scholar]
  31. 31.
    Hnatiuk AP, Briganti F, Staudt D, Mercola M. 2021. Human iPSC modeling of heart disease for drug development. Cell Chem. Biol. 28:3271–82
     [Google Scholar]
  32. 32.
    Holtzer H, Abbott J, Lash J, Holtzer S. 1960. The loss of phenotypic traits by differentiated cells in vitro, I. Dedifferentiation of cartilage cells. PNAS 46:121533–42
     [Google Scholar]
  33. 33.
    Hor P, Punj V, Calvert BA, Castaldi A, Miller AJ et al. 2020. Efficient generation and transcriptomic profiling of human iPSC-derived pulmonary neuroendocrine cells. iScience 23:5101083
     [Google Scholar]
  34. 34.
    Horani A, Ustione A, Huang T, Firth AL, Pan J et al. 2018. Establishment of the early cilia preassembly protein complex during motile ciliogenesis. PNAS 115:6E1221–28
     [Google Scholar]
  35. 35.
    Hu X, Mao C, Fan L, Luo H, Hu Z et al. 2020. Modeling Parkinson's disease using induced pluripotent stem cells. Stem Cells Int. 2020:1061470
     [Google Scholar]
  36. 36.
    Hung A, Housman G, Briscoe EA, Cuevas C, Gilad Y. 2021. Characterizing gene expression responses to biomechanical strain in an in vitro model of osteoarthritis. bioRxiv 2021.02.22.432314. https://doi.org/10.1101/2021.02.22.432314
  37. 37.
    Jacob A, Morley M, Hawkins F, McCauley KB, Jean JC et al. 2017. Differentiation of human pluripotent stem cells into functional lung alveolar epithelial cells. Cell Stem Cell 21:4472–88.e10
     [Google Scholar]
  38. 38.
    Jang J, Kang HC, Kim HS, Kim JY, Huh YJ et al. 2011. Induced pluripotent stem cell models from X-linked adrenoleukodystrophy patients. Ann. Neurol. 70:3402–9
     [Google Scholar]
  39. 39.
    Jennings S, Ng HP, Wang G. 2019. Establishment of a ΔF508-CF promyelocytic cell line for cystic fibrosis research and drug screening. J. Cyst. Fibros. 18:144–53
     [Google Scholar]
  40. 40.
    Joshi N, Walter JM, Misharin AV. 2018. Alveolar macrophages. Cell. Immunol. 330:86–90
     [Google Scholar]
  41. 41.
    Kanton S, Boyle MJ, He Z, Santel M, Weigert A et al. 2019. Organoid single-cell genomic atlas uncovers human-specific features of brain development. Nature 574:7778418–22
     [Google Scholar]
  42. 42.
    Kaserman JE, Hurley K, Dodge M, Villacorta-Martin C, Vedaie M et al. 2020. A highly phenotyped open access repository of alpha-1 antitrypsin deficiency pluripotent stem cells. Stem Cell Rep. 15:1242–55
     [Google Scholar]
  43. 43.
    Kawai S, Yoshitomi H, Sunaga J, Alev C, Nagata S et al. 2019. In vitro bone-like nodules generated from patient-derived iPSCs recapitulate pathological bone phenotypes. Nat. Biomed. Eng. 3:7558–70
     [Google Scholar]
  44. 44.
    Kaye JA, Finkbeiner S. 2013. Modeling Huntington's disease with induced pluripotent stem cells. Mol. Cell Neurosci. 56:50–64
     [Google Scholar]
  45. 45.
    Kuijlaars J, Oyelami T, Diels A, Rohrbacher J, Versweyveld S et al. 2016. Sustained synchronized neuronal network activity in a human astrocyte co-culture system. Sci. Rep. 6:36529
     [Google Scholar]
  46. 46.
    Lauing KL, Cortes M, Domowicz MS, Henry JG, Baria AT, Schwartz NB. 2014. Aggrecan is required for growth plate cytoarchitecture and differentiation. Dev. Biol. 396:2224–36
     [Google Scholar]
  47. 47.
    Lee S, Park C, Han JW, Kim JY, Cho K et al. 2017. Direct reprogramming of human dermal fibroblasts into endothelial cells using ER71/ETV2. Circ. Res. 120:5848–61
     [Google Scholar]
  48. 48.
    Livide G, Patriarchi T, Amenduni M, Amabile S, Yasui D et al. 2015. GluD1 is a common altered player in neuronal differentiation from both MECP2-mutated and CDKL5-mutated iPS cells. Eur. J. Hum. Genet. 23:2195–201
     [Google Scholar]
  49. 49.
    Lomas DA, Irving JA, Arico-Muendel C, Belyanskaya S, Brewster A et al. 2021. Development of a small molecule that corrects misfolding and increases secretion of Z α1-antitrypsin. EMBO Mol. Med. 13:3e13167
     [Google Scholar]
  50. 50.
    Lyra-Leite DM, Gutiérrez-Gutiérrez Ó, Wang M, Zhou Y, Cyganek L, Burridge PW. 2022. A review of protocols for human iPSC culture, cardiac differentiation, subtype-specification, maturation, and direct reprogramming. STAR Protoc. 3:3101560
     [Google Scholar]
  51. 51.
    Marchetto MCN, Carromeu C, Acab A, Yu D, Yeo GW et al. 2010. A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 143:4527–39
     [Google Scholar]
  52. 52.
    Marrone L, Poser I, Casci I, Japtok J, Reinhardt P et al. 2018. Isogenic FUS-eGFP iPSC reporter lines enable quantification of FUS stress granule pathology that is rescued by drugs inducing autophagy. Stem Cell Rep. 10:2375–89
     [Google Scholar]
  53. 53.
    McComish SF, Caldwell MA. 2018. Generation of defined neural populations from pluripotent stem cells. Philos. Trans. R. Soc. B 373:175020170214
     [Google Scholar]
  54. 54.
    McKeithan WL, Feyen DAM, Bruyneel AAN, Okolotowicz KJ, Ryan DA et al. 2020. Reengineering an antiarrhythmic drug using patient hiPSC cardiomyocytes to improve therapeutic potential and reduce toxicity. Cell Stem Cell 27:5813–21.e6
     [Google Scholar]
  55. 55.
    Mesquita FCP, Arantes PC, Kasai-Brunswick TH, Araujo DS, Gubert F et al. 2019. R534C mutation in hERG causes a trafficking defect in iPSC-derived cardiomyocytes from patients with type 2 long QT syndrome. Sci. Rep. 9:119203
     [Google Scholar]
  56. 56.
    Mianne J, Ahmed E, Bourguignon C, Fieldes M, Vachier I et al. 2018. Induced pluripotent stem cells for primary ciliary dyskinesia modeling and personalized medicine. Am. J. Respir. Cell Mol. Biol. 59:6672–83
     [Google Scholar]
  57. 57.
    Muratore CR, Rice HC, Srikanth P, Callahan DG, Shin T et al. 2014. The familial Alzheimer's disease APPV717I mutation alters APP processing and Tau expression in iPSC-derived neurons. Hum. Mol. Genet. 23:133523–36
     [Google Scholar]
  58. 58.
    Musunuru K, Sheikh F, Gupta RM, Houser SR, Maher KO et al. 2018. Induced pluripotent stem cells for cardiovascular disease modeling and precision medicine: a scientific statement from the American Heart Association. Circ. Genom. Precis. Med. 11:1e000043
     [Google Scholar]
  59. 59.
    Nagpal N, Wang J, Zeng J, Lo E, Moon DH et al. 2020. Small-molecule PAPD5 inhibitors restore telomerase activity in patient stem cells. Cell Stem Cell 26:6896–909.e8
     [Google Scholar]
  60. 60.
    Nakajima T, Shibata M, Nishio M, Nagata S, Alev C et al. 2018. Modeling human somite development and fibrodysplasia ossificans progressiva with induced pluripotent stem cells. Development 145:16dev165431
     [Google Scholar]
  61. 61.
    Naumann M, Pal A, Goswami A, Lojewski X, Japtok J et al. 2018. Impaired DNA damage response signaling by FUS-NLS mutations leads to neurodegeneration and FUS aggregate formation. Nat. Commun. 9:1335
     [Google Scholar]
  62. 62.
    Oksanen M, Petersen AJ, Naumenko N, Puttonen K, Lehtonen S et al. 2017. PSEN1 mutant iPSC-derived model reveals severe astrocyte pathology in Alzheimer's disease. Stem Cell Rep. 9:61885–97
     [Google Scholar]
  63. 63.
    Ou M, Li C, Tang D, Xue W, Xu Y et al. 2019. Genotyping, generation and proteomic profiling of the first human autosomal dominant osteopetrosis type II-specific induced pluripotent stem cells. Stem Cell Res. Ther. 10:1251
     [Google Scholar]
  64. 64.
    Pardo A, Selman M. 2016. Lung fibroblasts, aging, and idiopathic pulmonary fibrosis. Ann. Am. Thorac. Soc. 13:Suppl. 5S417–21
     [Google Scholar]
  65. 65.
    Piñeiro-Ramil M, Sanjurjo-Rodríguez C, Castro-Viñuelas R, Rodríguez-Fernández S, Fuentes-Boquete IM et al. 2019. Usefulness of mesenchymal cell lines for bone and cartilage regeneration research. Int. J. Mol. Sci. 20:246286
     [Google Scholar]
  66. 66.
    Poon EN, Hao B, Guan D, Li MJ, Lu J et al. 2018. Integrated transcriptomic and regulatory network analyses identify microRNA-200c as a novel repressor of human pluripotent stem cell-derived cardiomyocyte differentiation and maturation. Cardiovasc. Res. 114:6894–906
     [Google Scholar]
  67. 67.
    Rane A, Rajagopalan S, Ahuja M, Thomas B, Chinta SJ, Andersen JK. 2018. Hsp90 co-chaperone p23 contributes to dopaminergic mitochondrial stress via stabilization of PHD2: implications for Parkinson's disease. NeuroToxicology 65:166–73
     [Google Scholar]
  68. 68.
    Ren Y, Lee MY, Schliffke S, Paavola J, Amos PJ et al. 2011. Small molecule Wnt inhibitors enhance the efficiency of BMP-4-directed cardiac differentiation of human pluripotent stem cells. J. Mol. Cell. Cardiol. 51:3280–87
     [Google Scholar]
  69. 69.
    Ruaro B, Salton F, Braga L, Wade B, Confalonieri P et al. 2021. The history and mystery of alveolar epithelial type II cells: focus on their physiologic and pathologic role in lung. Int. J. Mol. Sci. 22:52566
     [Google Scholar]
  70. 70.
    Saitta B, Passarini J, Sareen D, Ornelas L, Sahabian A et al. 2014. Patient-derived skeletal dysplasia induced pluripotent stem cells display abnormal chondrogenic marker expression and regulation by BMP2 and TGFβ1. Stem Cells Dev. 23:131464–78
     [Google Scholar]
  71. 71.
    Scesa G, Adami R, Bottai D. 2021. iPSC preparation and epigenetic memory: Does the tissue origin matter?. Cells 10:61470
     [Google Scholar]
  72. 72.
    Schwab AJ, Ebert AD. 2015. Neurite aggregation and calcium dysfunction in iPSC-derived sensory neurons with Parkinson's disease-related LRRK2 G2019S mutation. Stem Cell Rep. 5:61039–52
     [Google Scholar]
  73. 73.
    Segeritz CP, Rashid ST, de Brito MC, Serra MP, Ordonez A et al. 2018. hiPSC hepatocyte model demonstrates the role of unfolded protein response and inflammatory networks in α1-antitrypsin deficiency. J. Hepatol. 69:4851–60
     [Google Scholar]
  74. 74.
    Shimoji K, Yuasa S, Onizuka T, Hattori F, Tanaka T et al. 2010. G-CSF promotes the proliferation of developing cardiomyocytes in vivo and in derivation from ESCs and iPSCs. Cell Stem Cell 6:3227–37
     [Google Scholar]
  75. 75.
    Shinozawa T, Nakamura K, Shoji M, Morita M, Kimura M et al. 2017. Recapitulation of clinical individual susceptibility to drug-induced QT prolongation in healthy subjects using iPSC-derived cardiomyocytes. Stem Cell Rep. 8:2226–34
     [Google Scholar]
  76. 76.
    Simsek S, Zhou T, Robinson CL, Tsai SY, Crespo M et al. 2016. Modeling cystic fibrosis using pluripotent stem cell-derived human pancreatic ductal epithelial cells. Stem Cells Transl. Med. 5:5572–79
     [Google Scholar]
  77. 77.
    Smethurst P, Risse E, Tyzack GE, Mitchell JS, Taha DM et al. 2020. Distinct responses of neurons and astrocytes to TDP-43 proteinopathy in amyotrophic lateral sclerosis. Brain 143:2430–40
     [Google Scholar]
  78. 78.
    Stattin EL, Wiklund F, Lindblom K, Onnerfjord P, Jonsson BA et al. 2010. A missense mutation in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans. Am. J. Hum. Genet. 86:2126–37
     [Google Scholar]
  79. 79.
    Steele-Stallard HB, Pinton L, Sarcar S, Ozdemir T, Maffioletti SM et al. 2018. Modeling skeletal muscle laminopathies using human induced pluripotent stem cells carrying pathogenic LMNA mutations. Front. Physiol. 9:1332
     [Google Scholar]
  80. 80.
    Strikoudis A, Cieślak A, Loffredo L, Chen YW, Patel N et al. 2019. Modeling of fibrotic lung disease using 3D organoids derived from human pluripotent stem cells. Cell Rep. 27:123709–23.e5
     [Google Scholar]
  81. 81.
    Strober BJ, Elorbany R, Rhodes K, Krishnan N, Tayeb K et al. 2019. Dynamic genetic regulation of gene expression during cellular differentiation. Science 364:64471287–90
     [Google Scholar]
  82. 82.
    Suzuki S, Crane AM, Anirudhan V, Barilla C, Matthias N et al. 2020. Highly efficient gene editing of cystic fibrosis patient-derived airway basal cells results in functional CFTR correction. Mol. Ther. 28:71684–95
     [Google Scholar]
  83. 83.
    Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T et al. 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:5861–72
     [Google Scholar]
  84. 84.
    Tam WL, Freitas Mendes L, Chen X, Lesage R, Van Hoven I et al. 2021. Human pluripotent stem cell-derived cartilaginous organoids promote scaffold-free healing of critical size long bone defects. Stem Cell Res. Ther. 12:1513
     [Google Scholar]
  85. 85.
    Umans BD, Battle A, Gilad Y. 2021. Where are the disease-associated eQTLs?. Trends Genet. 37:2109–24
     [Google Scholar]
  86. 86.
    Vaidyanathan S, Baik R, Chen L, Bravo DT, Suarez CJ et al. 2021. Targeted replacement of full-length CFTR in human airway stem cells by CRISPR-Cas9 for pan-mutation correction in the endogenous locus. Mol. Ther. 30:223–37
     [Google Scholar]
  87. 87.
    van Mil A, Balk GM, Neef K, Buikema JW, Asselbergs FW et al. 2018. Modelling inherited cardiac disease using human induced pluripotent stem cell-derived cardiomyocytes: progress, pitfalls, and potential. Cardiovasc. Res. 114:141828–42
     [Google Scholar]
  88. 88.
    Vander Roest AS, Liu C, Morck MM, Kooiker KB, Jung G et al. 2021. Hypertrophic cardiomyopathy β-cardiac myosin mutation (P710R) leads to hypercontractility by disrupting super relaxed state. PNAS 118:24e2025030118
     [Google Scholar]
  89. 89.
    Vandoorne T, Veys K, Guo W, Sicart A, Vints K et al. 2019. Differentiation but not ALS mutations in FUS rewires motor neuron metabolism. Nat. Commun. 10:14147
     [Google Scholar]
  90. 90.
    Wang Z, Wang L, Liu W, Hu D, Gao Y et al. 2019. Pathogenic mechanism and gene correction for LQTS-causing double mutations in KCNQ1 using a pluripotent stem cell model. Stem Cell Res 38:101483 Corrigendum 2019. Stem Cell Res. 41:101526
     [Google Scholar]
  91. 91.
    Werder RB, Huang J, Abo KM, Hix OT, Minakin K et al. 2022. Generating 3D spheres and 2D air-liquid interface cultures of human induced pluripotent stem cell-derived type 2 alveolar epithelial cells. J. Vis. Exp. 2022:182e63875
     [Google Scholar]
  92. 92.
    Wu C-L, Dicks A, Steward N, Tang R, Katz DB et al. 2021. Single cell transcriptomic analysis of human pluripotent stem cell chondrogenesis. Nat. Commun. 12:1362
     [Google Scholar]
  93. 93.
    Wyles SP, Li X, Hrstka SC, Reyes S, Oommen S et al. 2016. Modeling structural and functional deficiencies of RBM20 familial dilated cardiomyopathy using human induced pluripotent stem cells. Hum. Mol. Genet. 25:2254–65
     [Google Scholar]
  94. 94.
    Xu M, Stattin EL, Shaw G, Heinegard D, Sullivan G et al. 2016. Chondrocytes derived from mesenchymal stromal cells and induced pluripotent cells of patients with familial osteochondritis dissecans exhibit an endoplasmic reticulum stress response and defective matrix assembly. Stem Cells Transl. Med. 5:91171–81
     [Google Scholar]
  95. 95.
    Yao DW, O'Connor LJ, Price AL, Gusev A 2020. Quantifying genetic effects on disease mediated by assayed gene expression levels. Nat. Genet. 52:6626–33
     [Google Scholar]
  96. 96.
    Yoshida S, Miyagawa S, Fukushima S, Kawamura T, Kashiyama N et al. 2018. Maturation of human induced pluripotent stem cell-derived cardiomyocytes by soluble factors from human mesenchymal stem cells. Mol. Ther. 26:112681–95
     [Google Scholar]
  97. 97.
    Young JE, Fong LK, Frankowski H, Petsko GA, Small SA, Goldstein LSB. 2018. Stabilizing the retromer complex in a human stem cell model of Alzheimer's disease reduces TAU phosphorylation independently of amyloid precursor protein. Stem Cell Rep. 10:31046–58
     [Google Scholar]
  98. 98.
    Yu CH, Davidson S, Harapas CR, Hilton JB, Mlodzianoski MJ et al. 2020. TDP-43 triggers mitochondrial DNA release via mPTP to activate cGAS/STING in ALS. Cell 183:3636–49.e18
     [Google Scholar]
  99. 99.
    Zhang M, D'Aniello C, Verkerk AO, Wrobel E, Frank S et al. 2014. Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: disease mechanisms and pharmacological rescue. PNAS 111:50E5383–92
     [Google Scholar]
  100. 100.
    Zhao J, Davis MD, Martens YA, Shinohara M, Graff-Radford NR et al. 2017. APOE ε4/ε4 diminishes neurotrophic function of human iPSC-derived astrocytes. Hum. Mol. Genet. 26:142690–700
     [Google Scholar]
  101. 101.
    Zheng Z, Lu W, Pei Z, Chen J, Yang T, Luo F 2020. Generation of an induced pluripotent stem cell line (CHFUi001-A) from an osteogenesis imperfecta patient with COL1A2 mutation. Stem Cell Res. 47:101907
     [Google Scholar]
  102. 102.
    Ziegler T, Hinkel R, Kupatt C. 2018. Induced pluripotent stem cell derived cardiac models: effects of Thymosin β4. Expert Opin. Biol. Ther. 18:Suppl. 1111–20
     [Google Scholar]
/content/journals/10.1146/annurev-genet-022123-090319
Loading
Induced Pluripotent Stem Cells in Disease Biology and the Evidence for Their In Vitro Utility
Annual Review of Genetics 57, 341 (2023); https://doi.org/10.1146/annurev-genet-022123-090319
/content/journals/10.1146/annurev-genet-022123-090319
/content/journals/10.1146/annurev-genet-022123-090319
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error