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1. (WO2018204262) TRANSCRIPTION FACTORS CONTROLLING DIFFERENTIATION OF STEM CELLS
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Pub. No.: WO/2018/204262 International Application No.: PCT/US2018/030216
Publication Date: 08.11.2018 International Filing Date: 30.04.2018
IPC:
C12N 5/071 (2010.01) ,C12N 5/0735 (2010.01) ,C12N 5/0797 (2010.01)
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N
MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICRO-ORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
5
Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
07
Animal cells or tissues
071
Vertebrate cells or tissues, e.g. human cells or tissues
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N
MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICRO-ORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
5
Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
07
Animal cells or tissues
071
Vertebrate cells or tissues, e.g. human cells or tissues
073
Embryonic cells or tissues; Foetal cells or tissues
0735
Embryonic stem cells; Embryonic germ cells
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N
MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICRO-ORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
5
Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
07
Animal cells or tissues
071
Vertebrate cells or tissues, e.g. human cells or tissues
079
Neural cells
0797
Stem cells; Progenitor cells
Applicants:
PRESIDENT AND FELLOWS OF HARVARD COLLEGE [US/US]; 17 Quincy Street Cambridge, Massachusetts 02138, US
Inventors:
NG, Alex H.M.; US
CHURCH, George M.; US
BUSSKAMP, Volker; DE
Agent:
IWANICKI, John P.; US
Priority Data:
62/492,55201.05.2017US
62/517,30709.06.2017US
Title (EN) TRANSCRIPTION FACTORS CONTROLLING DIFFERENTIATION OF STEM CELLS
(FR) FACTEURS DE TRANSCRIPTION RÉGULANT LA DIFFÉRENCIATION DE CELLULES SOUCHES
Abstract:
(EN) Forced expression of a handful of transcription factors (TFs) can induce conversions between cell identities; however, the extent to which TFs can alter cell identity has not been systematically assessed. Here, we assembled a "human TFome," a comprehensive expression library of 1,578 human TF clones with full coverage of the major TF families. By systematically screening the human TFome, we identified many individual TFs that induce loss of human-induced-pluripotent-stem-cell (hiPSC) identity, suggesting a pervasive ability for TFs to alter cell identity. Using large-scale computational cell type classification trained on thousands of tissue expression profiles, we identified cell types generated by these TFs with high efficiency and speed, without additional selections or mechanical perturbations. TF expression in adult human tissues only correlated with some of the cell lineage generated, suggesting more complexity than observation studies can explain.
(FR) L'expression forcée d'un groupe de facteurs de transcription (TF) peut induire des conversions entre des identités cellulaires ; cependant, la mesure dans laquelle des TF peuvent modifier l'identité cellulaire n'a pas été systématiquement évaluée. Dans la présente invention, un "TFome humain" a été assemblé, qui est une banque d'expression complète de 1 578 clones de TF humains couvrant l'ensemble des principales familles de TF. Par le biais d'un criblage systématique du TFome humain, de nombreux TF individuels induisant une perte d’identité de cellule souche pluripotente induite humaine (hiPSC)) ont été identifiés, suggérant une capacité omniprésente des TF à modifier l'identité cellulaire. À l'aide d'une classification de type cellulaire informatique à grande échelle réalisée sur des milliers de profils d'expression de tissus, nous avons identifié des types cellulaires générés par ces TF avec une efficacité et une vitesse élevées, sans sélections supplémentaires ni perturbations mécaniques. L'expression de TF dans des tissus humains adultes n'est corrélée qu'avec une partie de la lignée cellulaire générée, suggérant ainsi une complexité plus importante par comparaison avec ce qu'il est possible d'expliquer par le biais d'études d'observation.
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Designated States: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW
African Regional Intellectual Property Organization (ARIPO) (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Office (AM, AZ, BY, KG, KZ, RU, TJ, TM)
European Patent Office (EPO) (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG)
Publication Language: English (EN)
Filing Language: English (EN)