Genome engineering of stem cell organoids for disease modeling

Yingmin Sun, Qiurong Ding

PDF(1465 KB)
PDF(1465 KB)
Protein Cell ›› 2017, Vol. 8 ›› Issue (5) : 315-327. DOI: 10.1007/s13238-016-0368-0
REVIEW
REVIEW

Genome engineering of stem cell organoids for disease modeling

Author information +
History +

Abstract

Precision medicine emerges as a new approach that takes into account individual variability. Successful realization of precision medicine requires disease models that are able to incorporate personalized disease information and recapitulate disease development processes at the molecular, cellular and organ levels. With recent development in stem cell field, a variety of tissue organoids can be derived from patient specific pluripotent stem cells and adult stem cells. In combination with the state-of-the-art genome editing tools, organoids can be further engineered to mimic diseaserelevant genetic and epigenetic status of a patient. This has therefore enabled a rapid expansion of sophisticated in vitro disease models, offering a unique system for fundamental and biomedical research as well as the development of personalized medicine. Here we summarize some of the latest advances and future perspectives in engineering stem cell organoids for human disease modeling.

Keywords

pluripotent/adult stem cell / tissue organoid / genome editing / precision medicine

Cite this article

Download citation ▾
Yingmin Sun, Qiurong Ding. Genome engineering of stem cell organoids for disease modeling. Protein Cell, 2017, 8(5): 315‒327 https://doi.org/10.1007/s13238-016-0368-0

References

[1]
AiharaE, MaheMM, SchumacherMA, MatthisAL, FengR, RenW, NoahTK, Matsu-uraT, MooreSR, HongCI (2015) Characterization of stem/progenitor cell cycle using murine circumvallate papilla taste bud organoid. Sci Rep5: 17185
CrossRef Google scholar
[2]
AmabileA, MigliaraA, CapassoP, BiffiM, CittaroD, NaldiniL, LombardoA (2016) Inheritable silencing of endogenous genes by hit-and-run targeted epigenetic editing. Cell167:219–232
CrossRef Google scholar
[3]
BarkerN, HuchM, KujalaP, van de WeteringM, SnippertHJ, van EsJH, SatoT, StangeDE, BegthelH, van den BornM (2010) Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell6:25–36
CrossRef Google scholar
[4]
BartfeldS, BayramT, van de WeteringM, HuchM, BegthelH, KujalaP, VriesR, PetersPJ, CleversH (2015) In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology148:126–136
CrossRef Google scholar
[5]
Ben-ZviD, MeltonDA (2015) Modeling human nutrition using human embryonic stem cells. Cell161:12–17
CrossRef Google scholar
[6]
BigorgneAE, FarinHF, LemoineR, MahlaouiN, LambertN, GilM, SchulzA, PhilippetP, SchlesserP, AbrahamsenTG (2014) TTC7A mutations disrupt intestinal epithelial apicobasal polarity. J Clin Invest124:328–337
CrossRef Google scholar
[7]
BojSF, HwangCI, BakerLA, ChioII, EngleDD, CorboV, JagerM, Ponz-SarviseM, TiriacH, SpectorMS (2015) Organoid models of human and mouse ductal pancreatic cancer. Cell160:324–338
CrossRef Google scholar
[8]
CanverMC, SmithEC, SherF, PinelloL, SanjanaNE, ShalemO, ChenDD, SchuppPG, VinjamurDS, GarciaSP (2015) BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis. Nature527:192–197
CrossRef Google scholar
[9]
ChenB, GilbertLA, CiminiBA, SchnitzbauerJ, ZhangW, LiGW, ParkJ, BlackburnEH, WeissmanJS, QiLS (2013) Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell155:1479–1491
CrossRef Google scholar
[10]
ChenS, SanjanaNE, ZhengK, ShalemO, LeeK, ShiX, ScottDA, SongJ, PanJQ, WeisslederR (2015) Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis. Cell160:1246–1260
CrossRef Google scholar
[11]
ChengAW, WangH, YangH, ShiL, KatzY, TheunissenTW, RangarajanS, ShivalilaCS, DadonDB, JaenischR (2013) Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system. Cell Res23:1163–1171
CrossRef Google scholar
[12]
ChuaCW, ShibataM, LeiM, ToivanenR, BarlowLJ, BergrenSK, BadaniKK, McKiernanJM, BensonMC, HibshooshH (2014) Single luminal epithelial progenitors can generate prostate organoids in culture. Nat Cell Biol16:951–961
CrossRef Google scholar
[13]
CollinsFS, VarmusH (2015) A new initiative on precision medicine. N Engl J Med372:793–795
CrossRef Google scholar
[14]
DekkersJF, WiegerinckCL, de JongeHR, BronsveldI, JanssensHM, de Winter-de GrootKM, BrandsmaAM, de JongNW, BijveldsMJ, ScholteBJ (2013) A functional CFTR assay using primary cystic fiborsis intestinal organoids. Nat Med19:939–945
CrossRef Google scholar
[15]
DeWardAD, CramerJ, LagasseE (2014) Celluar heterogeneity in the mouse esophagus implicates the presence of a nonquiescent epithelial stem cell population. Cell Rep9:701–711
CrossRef Google scholar
[16]
DingQ, LeeYK, SchaeferEA, PetersDT, VeresA, KimK, KuperwasserN, MotolaDL, MeissnerTB, HendriksWT (2013) A TALEN genome-editing system for generating human stem cell-based disease models. Cell Stem Cell12:238–251
CrossRef Google scholar
[17]
DrostJ, van JaarsveldRH, PonsioenB, ZimberlinC, van BoxtelR, BuijsA, SachsN, OvermeerRM, OfferhausGJ, BegthelH (2015) Sequential cancer mutations in cultured human intestinal stem cells. Nature521:43–47
CrossRef Google scholar
[18]
DyeBR, HillDR, FergusonMA, TsaiYH, NagyMS, DyalR, WellsJM, MayhewCN, NattivR, KleinOD (2015) In vitro generation of human pluripotent stem cell derived lung organoids. Elife. doi:10.7554/eLife.05098
CrossRef Google scholar
[19]
EirakuM, WatanabeK, Matsuo-TakasakiM, KawadaM, YonemuraS, MatsumuraM, WatayaT, NishiyamaA, MugurumaK, SasaiY (2008) Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals. Cell Stem Cell3:519–532
CrossRef Google scholar
[20]
EirakuM, TakataN, IshibashiH, KawadaM, SakakuraE, OkudaS, SekiguchiK, AdachiT, SasaiY (2011) Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature472:51–56
CrossRef Google scholar
[21]
ForbesterJL, GouldingD, VallierL, HannanN, HaleC, PickardD, MukhopadhyayS, DouganG (2015) Interaction of Salmonella enterica Serovar Typhimurium with intestinal organoids derived from human induced pluripotent stem cells. Infect Immun83:2926–2934
CrossRef Google scholar
[22]
GaoD, VelaI, SbonerA, IaquintaPJ, KarthausWR, GopalanA, DowlingC, WanjalaJN, UndvallEA, AroraVK (2014) Organoid cultures derived from patients with advanced prostate cancer. Cell159:176–187
CrossRef Google scholar
[23]
GaspardN, BouschetT, HourezR, DimidschsteinJ, NaeijeG, van den AmeeleJ, Espuny-CamachoI, HerpoelA, PassanteL, SchiffmannSN (2008) An intrinsic mechanism of corticogenesis from embryonic stem cells. Nature455:351–357
CrossRef Google scholar
[24]
GilbertLA, LarsonMH, MorsutL, LiuZ, BrarGA, TorresSE, Stern-GinossarN, BrandmanO, WhiteheadEH, DoudnaJA (2013) CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell154:442–451
CrossRef Google scholar
[25]
GilbertLA, HorlbeckMA, AdamsonB, VillaltaJE, ChenY, WhiteheadEH, GuimaraesC, PanningB, PloeghHL, BassikMC (2014) Genome-scale CRISPR-mediated control of gene repression and activation. Cell159:647–661
CrossRef Google scholar
[26]
HiltonIB, D’IppolitoAM, VockleyCM, ThakorePI, CrawfordGE, ReddyTE, GersbachCA (2015) Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nat Biotechnol33:510–517
CrossRef Google scholar
[27]
HishaH, TanakaT, KannoS, TokuyamaY, KomaiY, OheS, YanaiH, OmachiT, UenoH (2013) Establishment of a novel lingual organoid culture system: generation of organoids having mature keratinized epithelium from adult epithelial stem cells. Sci Rep3:3224
CrossRef Google scholar
[28]
HsuPD, LanderES, ZhangF (2014) Development and applications of CRISPR-Cas9 for genome engineering. Cell157:1262–1278
CrossRef Google scholar
[29]
HuchM, BonfantiP, BojSF, SatoT, LoomansCJ, van de WeteringM, SojoodiM, LiVS, SchuijersJ, GracaninA (2013a) Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis. EMBO J32:2708–2721
CrossRef Google scholar
[30]
HuchM, DorrellC, BojSF, van EsJH, LiVS, van de WeteringM, SatoT, HamerK, SasakiN, FinegoldMJ (2013b) In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature494:247–250
CrossRef Google scholar
[31]
HuchM, GehartH, van BoxtelR, HamerK, BlokzijlF, VerstegenMM, EllisE, van WenumM, FuchsSA, de LigtJ (2015) Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell160:299–312
CrossRef Google scholar
[32]
JainIH, ZazzeronL, GoliR, AlexaK, Schatzman-BoneS, DhillonH, GoldbergerO, PengJ, ShalemO, SanjanaNE (2016) Hypoxia as a therapy for mitochondrial disease. Science 352:54–61
CrossRef Google scholar
[33]
JungP, SatoT, Merlos-SuárezA, BarrigaFM, IglesiasM, RossellD, AuerH, GallardoM, BlascoMA, SanchoE (2011) Isolation and in vitro expansion of human colonic stem cells. Nat Med17:1225–1227
CrossRef Google scholar
[34]
KarthausWR, IaquintaPJ, DrostJ, GracaninA, van BoxtelR, WongvipatJ, DowlingCM, GaoD, BegthelH, SachsN (2014) Identification of multipotent luminal progenitor cells in human prostate organoid cultures. Cell159:163–175
CrossRef Google scholar
[35]
KearnsNA, PhamH, TabakB, GengaRM, SilversteinNJ, GarberM, MaehrR (2015) Functional annotation of native enhancers with a Cas9-histone demethylase fusion. Nat Methods12:401–403
CrossRef Google scholar
[36]
KoehlerKR, HashinoE (2014) 3D mouse embryonic stem cell culture for generating inner ear organoids. Nat Protoc9:1229–1244
CrossRef Google scholar
[37]
KoehlerKR, MikoszAM, MoloshAI, PatelD, HashinoE (2013) Generation of inner ear sensory epithelia from pluripotent stem cells in 3D culture. Nature500:217–221
CrossRef Google scholar
[38]
Koike-YusaH, LiY, TanEP, Velasco-Herrera MdelC, YusaK (2014) Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library. Nat Biotechnol32:267–273
CrossRef Google scholar
[39]
KomorAC, KimYB, PackerMS, ZurisJA, LiuDR (2016) Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature533:420–424
CrossRef Google scholar
[40]
KonermannS, BrighamMD, TrevinoAE, JoungJ, AbudayyehOO, BarcenaC, HsuPD, HabibN, GootenbergJS, NishimasuH (2015) Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature517:583–588
CrossRef Google scholar
[41]
KubbenN, ZhangW, WangL, VossTC, YangJ, QuJ, LiuGH, MisteliT (2016) Repression of the antioxidant NRF2 pathway in premature aging. Cell165:1361–1374
CrossRef Google scholar
[42]
LancasterMA, KnoblichJA (2014) Generation of cerebral organoids from human pluripotent stem cells. Nat Protoc9:2329–2340
CrossRef Google scholar
[43]
LancasterMA, RennerM, MartinCA, WenzelD, BicknellLS, HurlesME, HomfrayT, PenningerJM, JacksonAP, KnoblichJA (2013) Cerebral organoids model human brain development and microcephaly. Nature501:373–379
CrossRef Google scholar
[44]
LeeJH, BhangDH, BeedeA, HuangTL, StrippBR, BlochKD, WagersAJ, TsengYH, RyeomS, KimCF (2014) Lung stem cell differentiation in mice directed by endothelial cells via a BMP4-NFATc1-thrombospondin-1 axis. Cell156:440–455
CrossRef Google scholar
[45]
LeslieJL, HuangS, OppJS, NagyMS, KobayashiM, YoungVB, SpenceJR (2015) Persistence and toxin production by Clostridium difficile within human intestinal organoids result in disruption of epithelial paracellular barrier function. Infect Immun83:138–145
CrossRef Google scholar
[46]
LiY, ZhangW, ChangL, HanY, SunL, GongX, TangH, LiuZ, DengH, YeY (2016) Vitamin C alleviates aging defects in a stem cell model for Werner syndrome. Protein Cell7:478–488
CrossRef Google scholar
[47]
LiuGH, SuzukiK, QuJ, Sancho-MartinezI, YiF, LiM, KumarS, NivetE, KimJ, SoligallaRD (2011) Targeted gene correction of laminopathy-associated LMNA mutations in patient-specific iPSCs. Cell Stem Cell8:688–694
CrossRef Google scholar
[48]
MaH, TuLC, NaseriA, HuismanM, ZhangS, GrunwaldD, PedersonT (2016a) Multiplexed labeling of genomic loci with dCas9 and engineered sgRNAs using CRISPRainbow. Nat Biotechnol34:528–530
CrossRef Google scholar
[49]
MaY, ZhangJ, YinW, ZhangZ, SongY, ChangX (2016b) Targeted AID-mediated mutagenesis(TAM) enables efficient genomic diversification in mammalian cells. Nat Methods. doi:10.1038/nmeth.4027
CrossRef Google scholar
[50]
MarianiJ, SimoniniMV, PalejevD, TomasiniL, CoppolaG, SzekelyAM, HorvathTL, VaccarinoFM (2012) Modeling human cortical development in vitro using induced pluripotent stem cells. Proc Nati Acad Sci USA109:12770–12775
CrossRef Google scholar
[51]
MarianiJ, CoppolaG, ZhangP, AbyzovA, ProviniL, TomasiniL, AmenduniM, SzekelyA, PalejevD, WilsonM (2015) FOXG1-dependent dysregulation of GABA/Glutamate neuron differentiation of autism spectrum disorders. Cell162:375–390
CrossRef Google scholar
[52]
MaschmeyerI, LorenzAK, SchimekK, HasenbergT, RammeAP, HübnerJ, LindnerM, DrewellC, BauerS, ThomasA (2015) A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. Lab Chip15:2688–2699
CrossRef Google scholar
[53]
MatanoM, DateS, ShimokawaM, TakanoA, FujiiM, OhtaY, WatanabeT, KanaiT, SatoT (2015) Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. Nat Med21:256–262
CrossRef Google scholar
[54]
McCrackenKW, HowellJC, WellsJM, SpenceJR (2011) Generating human intestinal tissue from pluripotent stem cells in vitro. Nat Protoc6:1920–1928
CrossRef Google scholar
[55]
McCrackenKW, CatáEM, CrawfordCM, SinagogaKL, SchumacherM, RockichBE, TsaiYH, MayhewCN, SpenceJR, ZavrosY (2014) Modeling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature516:400–404
CrossRef Google scholar
[56]
MondrinosMJ, KoutzakiS, JiwanmallE, LiM, DechadarevianJP, LelkesPI, FinckCM (2006) Engineering three-dimensional pulmonary tissue constructs. Tissue Eng12:717–728
CrossRef Google scholar
[57]
MondrinosMJ, JonesPL, FinckCM, LelkesPI (2014) Engineering de novo assembly of fetal pulmonary organoids. Tissue Eng Part A20:2892–2907
CrossRef Google scholar
[58]
MugurumaK, NishiyamaA, OnoY, MiyawakiH, MizuharaE, HoriS, KakizukaA, ObataK, YanagawaY, HiranoT (2010) Ontogeny-recapitulating generation and tissue integration of ES cell-derived Purkinje cells. Nat Neurosci13:1171–1180
CrossRef Google scholar
[59]
MugurumaK, NishiyamaA, KawakamiH, HashimotoK, SasaiY (2015) Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells. Cell Rep10:537–550
CrossRef Google scholar
[60]
MusunuruK (2013) Genome editing of human pluripotent stem cells to generate human cellular disease models. Dis Model Mech6:896–904
CrossRef Google scholar
[61]
NanduriLS, BaanstraM, FaberH, RocchiC, ZwartE, de HaanG, van OsR, CoppesRP (2014) Purification and ex vivo expansion of fully functional salivary gland stem cells. Stem Cell Reports3:957–964
CrossRef Google scholar
[62]
NellesDA, FangMY, O’ConnellMR, XuJL, MarkmillerSJ, DoudnaJA, YeoGW (2016) Programmable RNA tracking in live cells with CRISPR/Cas9. Cell165:488–496
CrossRef Google scholar
[63]
NishidaK, ArazoeT, YachieN, BannoS, KakimotoM, TabataM, MochizukiM, MiyabeA, ArakiM, HaraKY (2016) Targeted nucleotide editing using hybrid prokaryotic and vertebrate adaptive immune systems. Science. doi:10.1126/science.aaf8729
[64]
NoguchiTK, NinomiyaN, SekineM, KomazakiS, WangPC, AsashimaM, KurisakiA (2015) Generation of stomch tissue from mosue embryonic stem cell. Nat Cell Biol17:984–993
CrossRef Google scholar
[65]
OgawaM, OgawaS, BearCE, AhmadiS, ChinS, LiB, GrompeM, KellerG, KamathBM, GhanekarA (2015) Directed differentiation of cholangiocytes from human pluripotent stem cells. Nat Biotechnol33:853–861
CrossRef Google scholar
[66]
OotaniA, LiX, SangiorgiE, HoQT, UenoH, TodaS, SugiharaH, FujimotoK, WeissmanIL, CapecchiMR (2009) Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. Nat Med15:701–706
CrossRef Google scholar
[67]
OzoneC, SugaH, EirakuM, KadoshimaT, YonemuraS, TakataN, OisoY, TsujiT, SasaiY (2016) Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells. Nat Commun7:10351
CrossRef Google scholar
[68]
ParnasO, JovanovicM, EisenhaureTM, HerbstRH, DixitA, YeCJ, PrzybylskiD, PlattRJ, TiroshI, SanjanaNE (2015) A Genome-wide CRISPR screen in primary immune cells to dissect regulatory networks. Cell162:675–686
CrossRef Google scholar
[69]
Perez-PineraP, KocakDD, VockleyCM, AdlerAF, KabadiAM, PolsteinLR, ThakorePI, GlassKA, OusteroutDG, LeongKW (2013a) RNA-guided gene activation by CRISPR-Cas9-based transcription factors. Nat Methods10:973–976
CrossRef Google scholar
[70]
Perez-PineraP, OusteroutDG, BrungerJM, FarinAM, GlassKA, GuilakF, CrawfordGE, HarteminkAJ, GersbachCA (2013b) Synergistic and tunable human gene activation by combinations of synthetic transcription factors. Nat Methods10:239–242
CrossRef Google scholar
[71]
QiLS, LarsonMH, GilbertLA, DoudnaJA, WeissmanJS, ArkinAP, LimWA (2013) Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell152:1173–1183
CrossRef Google scholar
[72]
QianX, NguyenHN, SongMM, HadionoC, OgdenSC, HammackC, YaoB, HamerskyGR, JacobF, ZhongC (2016) Brainregion-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell165:1238–1254
CrossRef Google scholar
[73]
RenW, LewandowskiBC, WatsonJ, AiharaE, IwatsukiK, BachmanovAA, MargolskeeRF, JiangP (2014) Single Lgr5- or Lgr6- expressing taste stem/progenitor cells generate taste bud cells ex vivo. Proc Natl Acad Sci USA111:16401–16406
CrossRef Google scholar
[74]
SampaziotisF, Cardoso de BritoM, MadrigalP, BerteroA, Saeb-ParsyK, SoaresFA, SchrumpfE, MelumE, KarlsenTH, BradleyJA (2015) Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation. Nat Biotechnol33:845–852
CrossRef Google scholar
[75]
SanjanaNE, WrightJ, ZhengK, ShalemO, FontanillasP, JoungJ, ChengC, RegevA, ZhangF (2016) High-resolution interrogation of functional elements in the noncoding genome. Science353:1545–1549
CrossRef Google scholar
[76]
SatoT, VriesRG, SnippertHJ, van de WeteringM, BarkerN, StangeDE, van EsJH, AboA, KujalaP, PetersPJ (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature459:262–265
CrossRef Google scholar
[77]
SatoT, StangeDE, FerranteM, VriesRG, Van EsJH, Van den BrinkS, Van HoudtWJ, PronkA, Van GorpJ (2011) Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology141:1762–1772
CrossRef Google scholar
[78]
SchlaermannP, ToelleB, BergerH, SchmidtSC, GlanemannM, OrdemannJ, BartfeldS, MollenkopfHJ, MeyerTF (2016) A novel human gastric primary cell culture system for modeling Helicobacter pylori infection in vitro. Gut65:201–213
CrossRef Google scholar
[79]
SchmidtJC, ZaugAJ, CechTR (2016) Live cell imaging reveals the dynamics of telomerase recruitment to telomeres. Cell166:1188–1197
CrossRef Google scholar
[80]
SchweigerPJ, JensenKB (2016) Modeling human disease using organotypic cultures. Curr Opin Cell Biol43:22–29
CrossRef Google scholar
[81]
ShalemO, SanjanaNE, HartenianE, ShiX, ScottDA, MikkelsenTS, HecklD, EbertBL, RootDE, DoenchJG (2014) Genomescale CRISPR-Cas9 knockout screening in human cells. Science343:84–87
CrossRef Google scholar
[82]
ShiJ, ZhaoY, WangK, ShiX, WangY, HuangH, ZhuangY, CaiT, WangF, ShaoF (2015) Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature526:660–665
CrossRef Google scholar
[83]
SpenceJR, MayhewCN, RankinSA, KuharMF, VallanceJE, TolleK, HoskinsEE, KalinichenkoVV, WellsSI, ZornAM (2011) Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature470:105–109
CrossRef Google scholar
[84]
StangeDE, KooBK, HuchM, SibbelG, BasakO, LyubimovaA, KujalaP, BartfeldS, KosterJ, GeahlenJH (2013) Differentiated Troy+ chife cells act as reserve stem cells to generate all lineages of the stomach epithelium. Cell155:357–368
CrossRef Google scholar
[85]
SugaH, KadoshimaT, MinaguchiM, OhgushiM, SoenM, NakanoT, TakataN, WatayaT, MugurumaK, MiyoshiH (2011) Selfformation of functional adenohypophysis in three-dimensional culture. Nature480:57–62
CrossRef Google scholar
[86]
TakahashiK, TanabeK, OhnukiM, NaritaM, IchisakaT, TomodaK, YamanakaS (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell131:861–872
CrossRef Google scholar
[87]
TakasatoM, ErPX, ChiuHS, MaierB, BaillieGJ, FergusonC, PartonRG, WolvetangEJ, RoostMS, de SousaChuva, LopesSM (2015) Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature526:564–568
CrossRef Google scholar
[88]
TakebeT, SekineK, EnomuraM, KoikeH, KimuraM, OgaeriT, ZhangRR, UenoY, ZhengYW, KoikeN (2013) Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature499:481–484
CrossRef Google scholar
[89]
TakebeT, ZhangRR, KoikeH, KimuraM, YoshizawaE, EnomuraM, KoikeN, SekineK, TaniguchiH (2014) Generation of a vascularized and functional human liver from an iPSC-derived organ bud transplant. Nat Protoc9:396–409
CrossRef Google scholar
[90]
ThakorePI, D’IppolitoAM, SongL, SafiA, ShivakumarNK, KabadiAM, ReddyTE, CrawfordGE, GersbachCA (2015) Highly specific epigenome editing by CRISPR-Cas9 repressors for silencing of distal regulatory elements. Nat Methods12:1143–1149
CrossRef Google scholar
[91]
van de WeteringM, FranciesHE, FrancisJM, BounovaG, IorioF, PronkA, van HoudtW, van GorpJ, Taylor-WeinerA, KesterL (2015) Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell161:933–945
CrossRef Google scholar
[92]
ViscontiRP, KasyanovV, GentileC, ZhangJ, MarkwaldRR, MironovV (2010) Towards organ printing: engineering an intra-organ branched vascular tree. Expert Opin Biol Ther10:409–420
CrossRef Google scholar
[93]
WangF, QiLS (2016) Applications of CRISPR genome engineering in cell biology. Trends Cell Biol26:875–888
CrossRef Google scholar
[94]
WangT, WeiJJ, SabatiniDM, LanderES (2014) Genetic screens in human cells using the CRISPR-Cas9 system. Science343:80–84
CrossRef Google scholar
[95]
WangX, YamamotoY, WilsonLH, ZhangT, HowittBE, FarrowMA, KernF, NingG, HongY, KhorCC (2015) Cloning and variation of ground state intestinal stem cells. Nature522:173–178
CrossRef Google scholar
[96]
WatsonCL, MaheMM, MúneraJ, HowellJC, SundaramN, PolingHM, SchweitzerJI, VallanceJE, MayhewCN, SunY (2014) An in vivo model of human small intestine using pluripotent stem cells. Nat Med20:1310–1314
CrossRef Google scholar
[97]
WilsonSS, TocchiA, HollyMK, ParksWC, SmithJG (2015) A small intestinal organoid model of non-invasive enteric pathogenepithelial cell interactions. Mucosal Immunol8:352–361
CrossRef Google scholar
[98]
WorkmanMJ, MaheMM, TrisnoS, PolingHM, WatsonCL, SundaramN, ChangCF, SchiesserJ, AubertP, StanleyEG (2016) Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system. Nat Med. doi: 10.1038/nm.4233
CrossRef Google scholar
[99]
WroblewskiLE, PiazueloMB, ChaturvediR, SchumacherM, AiharaE, FengR, NotoJM, DelgadoA, IsraelDA, ZavrosY (2015) Helicobacter pylori targets cancer-associated apical-junctional constituents in gastroids and gastric epithelial cells. Gut64:720–730
CrossRef Google scholar
[100]
YinX, FarinHF, van EsJH, CleversH, LangerR, KarpJM (2014) Niche-independent high-purify cultures of Lgr5+ intestinal stem cells and their progeny. Nat Methods11:106–112
CrossRef Google scholar
[101]
YinX, MeadBE, SafaeeH, LangerR, KarpJM, LevyO (2016) Engieering stem cell organoids. Cell Stem Cell18:25–38
CrossRef Google scholar
[102]
YuJ, VodyanikMA, Smuga-OttoK, Antosiewicz-BourgetJ, FraneJL, TianS, NieJ, JonsdottirGA, RuottiV, StewartR (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science318:1917–1920
CrossRef Google scholar
[103]
ZhangYG, WuS, XiaY, SunJ (2014) Salmonella-infected cryptderived intestinal organoid culture system for host-bacterial interactions. Physiol Rep2(9):e12147
CrossRef Google scholar
[104]
ZhangW, LiJ, SuzukiK, QuJ, WangP, ZhouJ, LiuX, RenR, XuX, OcampoA (2015) A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging. Science348:1160–1163
CrossRef Google scholar
[105]
ZhouY, ZhuS, CaiC, YuanP, LiC, HuangY, WeiW (2014) Highthroughput screening of a CRISPR/Cas9 library for functional genomics in human cells. Nature509:487–491
CrossRef Google scholar
[106]
ZhuS, LiW, LiuJ, ChenCH, LiaoQ, XuP, XuH, XiaoT, CaoZ, PengJ (2016) Genome-scale deletion screening of human long non-coding RNAs using a paired-guided RNA CRISPRCas9 library. Nat Biotechnol. doi: 10.1038/nbt.3715
CrossRef Google scholar

RIGHTS & PERMISSIONS

2017 The Author(s) 2017. This article is published with open access at Springerlink.com and journal.hep.com.cn
AI Summary AI Mindmap
PDF(1465 KB)

Accesses

Citations

Detail

Sections
Recommended

/