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Understanding how cellular identity naturally interconverts with high efficiency and temporospatial precision is crucial for regenerative medicine. Here, we revealed a natural midgut-to-renal lineage conversion event during Drosophila metamorphosis and identified the evolutionarily-conserved homeodomain protein Cut as a master switch in this process. A steep Wnt/Wingless morphogen gradient intersects with a pulse of steroid hormone ecdysone to induce cut expression in a subset of midgut progenitors and reprogram them into renal progenitors. Molecularly, ecdysone-induced temporal factor Broad physically interacts with cut enhancer-bound Wnt pathway effector TCF/β-catenin and likely bridges the distant enhancer and promoter region of cut through its self-association. Such long-range enhancer-promoter looping could subsequently trigger timely cut transcription. Our results therefore led us to propose an unexpected poising-and-bridging mechanism whereby spatial and temporal cues intersect, likely via chromatin looping, to turn on a master transcription factor and dictate efficient and precise lineage reprogramming.
Pubmed ID: 29714689 RIS Download
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Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsCollects, maintains and distributes Drosophila melanogaster strains for research. Emphasis is placed on genetic tools that are useful to a broad range of investigations. These include basic stocks of flies used in genetic analysis such as marker, balancer, mapping, and transposon-tagging strains; mutant alleles of identified genes, including a large set of transposable element insertion alleles; defined sets of deficiencies and a variety of other chromosomal aberrations; engineered lines for somatic and germline clonal analysis; GAL4 and UAS lines for targeted gene expression; enhancer trap and lacZ-reporter strains with defined expression patterns for marking tissues; and a collection of transposon-induced lethal mutations.
View all literature mentionsA commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.
View all literature mentionsSoftware for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.
View all literature mentionsServes Drosophila research community by collecting and distributing DNA clones and vectors; collecting and distributing Drosophila cell lines; developing and testing genomics technologies for use in Drosophila and assisting members of the research community in their use.
View all literature mentionsThis monoclonal targets allatostatin (Ast7)
View all literature mentionsThis monoclonal targets Bruchpilot
View all literature mentionsThis monoclonal targets Prospero protein
View all literature mentionsThis monoclonal targets Mouse Drosophila Cut protein product
View all literature mentionsThis monoclonal targets Broad (Z1)
View all literature mentionsThis monoclonal targets Broad (core)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsDrosophila melanogaster with name w[*] ct[C145] P{ry[+t7.2]=neoFRT}19A/FM7c; P{w[+mC]=UAS-ct.P}2, P{w[+mC]=UAS-mCD8::GFP.L}LL5/CyO from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00017}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02257}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02515}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00844}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00272}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00401}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02585}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00924}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[1118]; P{w[+mC]=UAS-pan.dTCF}4 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-br.Z4}37-6 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-br.Z3}216-1 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-br.Z1}18-13 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-EcR.B1-DeltaC655.W650A}TP1-9 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-sgg.S9A}MB14 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+m*]=NRE-EGFP.S}5A from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{y[+t7.7] w[+mC]=GMR35B08-GAL4}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-mCD8.ChRFP}3 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; TI{TI}Rab3[EYFP] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; sna[Sco]/CyO, P{ry[+t7.2]=en1}wg[en11] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[1118]; P{w[+mC]=UAS-pan.dTCFDeltaN}5 from BDSC.
View all literature mentionsDrosophila melanogaster with name P{w[+mC]=UAS-arm.S10}C, y[1] w[1118] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-wg.H.T:HA1}6C from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*] dsh[3] P{ry[+t7.2]=neoFRT}19A/FM7a from BDSC.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
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