Genome engineering of stem cell organoids for disease modeling
Yingmin Sun, Qiurong Ding
Genome engineering of stem cell organoids for disease modeling
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.
pluripotent/adult stem cell / tissue organoid / genome editing / precision medicine
[1] |
AiharaE, MaheMM, SchumacherMA, MatthisAL, FengR, RenW, NoahTK, Matsu-uraT, MooreSR, HongCI
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
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
CrossRef
Google scholar
|
[7] |
BojSF, HwangCI, BakerLA, ChioII, EngleDD, CorboV, JagerM, Ponz-SarviseM, TiriacH, SpectorMS
CrossRef
Google scholar
|
[8] |
CanverMC, SmithEC, SherF, PinelloL, SanjanaNE, ShalemO, ChenDD, SchuppPG, VinjamurDS, GarciaSP
CrossRef
Google scholar
|
[9] |
ChenB, GilbertLA, CiminiBA, SchnitzbauerJ, ZhangW, LiGW, ParkJ, BlackburnEH, WeissmanJS, QiLS
CrossRef
Google scholar
|
[10] |
ChenS, SanjanaNE, ZhengK, ShalemO, LeeK, ShiX, ScottDA, SongJ, PanJQ, WeisslederR
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
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
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
CrossRef
Google scholar
|
[17] |
DrostJ, van JaarsveldRH, PonsioenB, ZimberlinC, van BoxtelR, BuijsA, SachsN, OvermeerRM, OfferhausGJ, BegthelH
CrossRef
Google scholar
|
[18] |
DyeBR, HillDR, FergusonMA, TsaiYH, NagyMS, DyalR, WellsJM, MayhewCN, NattivR, KleinOD
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
CrossRef
Google scholar
|
[23] |
GaspardN, BouschetT, HourezR, DimidschsteinJ, NaeijeG, van den AmeeleJ, Espuny-CamachoI, HerpoelA, PassanteL, SchiffmannSN
CrossRef
Google scholar
|
[24] |
GilbertLA, LarsonMH, MorsutL, LiuZ, BrarGA, TorresSE, Stern-GinossarN, BrandmanO, WhiteheadEH, DoudnaJA
CrossRef
Google scholar
|
[25] |
GilbertLA, HorlbeckMA, AdamsonB, VillaltaJE, ChenY, WhiteheadEH, GuimaraesC, PanningB, PloeghHL, BassikMC
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
CrossRef
Google scholar
|
[30] |
HuchM, DorrellC, BojSF, van EsJH, LiVS, van de WeteringM, SatoT, HamerK, SasakiN, FinegoldMJ
CrossRef
Google scholar
|
[31] |
HuchM, GehartH, van BoxtelR, HamerK, BlokzijlF, VerstegenMM, EllisE, van WenumM, FuchsSA, de LigtJ
CrossRef
Google scholar
|
[32] |
JainIH, ZazzeronL, GoliR, AlexaK, Schatzman-BoneS, DhillonH, GoldbergerO, PengJ, ShalemO, SanjanaNE
CrossRef
Google scholar
|
[33] |
JungP, SatoT, Merlos-SuárezA, BarrigaFM, IglesiasM, RossellD, AuerH, GallardoM, BlascoMA, SanchoE
CrossRef
Google scholar
|
[34] |
KarthausWR, IaquintaPJ, DrostJ, GracaninA, van BoxtelR, WongvipatJ, DowlingCM, GaoD, BegthelH, SachsN
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
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
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
CrossRef
Google scholar
|
[52] |
MaschmeyerI, LorenzAK, SchimekK, HasenbergT, RammeAP, HübnerJ, LindnerM, DrewellC, BauerS, ThomasA
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
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
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
|
[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
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
CrossRef
Google scholar
|
[69] |
Perez-PineraP, KocakDD, VockleyCM, AdlerAF, KabadiAM, PolsteinLR, ThakorePI, GlassKA, OusteroutDG, LeongKW
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
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
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
CrossRef
Google scholar
|
[77] |
SatoT, StangeDE, FerranteM, VriesRG, Van EsJH, Van den BrinkS, Van HoudtWJ, PronkA, Van GorpJ
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
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
CrossRef
Google scholar
|
[84] |
StangeDE, KooBK, HuchM, SibbelG, BasakO, LyubimovaA, KujalaP, BartfeldS, KosterJ, GeahlenJH
CrossRef
Google scholar
|
[85] |
SugaH, KadoshimaT, MinaguchiM, OhgushiM, SoenM, NakanoT, TakataN, WatayaT, MugurumaK, MiyoshiH
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
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
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
CrossRef
Google scholar
|
[96] |
WatsonCL, MaheMM, MúneraJ, HowellJC, SundaramN, PolingHM, SchweitzerJI, VallanceJE, MayhewCN, SunY
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
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
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
CrossRef
Google scholar
|
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