ENA0000GenomicsMeissner Lab, Harvard Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA255422Mus musculusDirect lineage conversion is a promising approach to generate therapeutically important cell types for disease modeling and tissue repair. However, it is often unclear whether lineage-reprogrammed cells remain stable long-term and whether the properties of the reprogrammed cells evolve over time. Here, using an improved method of converting pancreatic acinar cells to beta-cells, we show that induced beta-cells persist in the adult pancreas for up to 14 months and form islet-like structures. Detailed analyses of induced cells over 7 months reveal that global DNA methylation changes occur rapidly whereas transcription network remodeling evolves over two months to resemble that of endogenous beta-cells and then stabilizes thereafter. Progressive gain of beta-cell function by converted cells during the 7 month period coincides with both transcriptional changes and the formation of islet-like structures. These studies demonstrate the ability of lineage-reprogrammed cells to achieve a stable state and identify key cellular and molecular milestones during their long-term evolution. Overall design: Acinar cells and beta cells were collected as control, as well as induced beta cell samples at day 10, day 30, day 60, and 7 monthsENAd230, Effects, e(-), DELTA AND GAMMA, dTAFII250, electron, betaTub1, EfW1, Long Term, dmTAF[[II]]230, period, B1t, B-spec, dmTAF1, Taf230, betaspec, Effect, TAF250, Taf200, betatub(56D), dTAF[[II]]250, kus, beta1tub, TFIID TAF250, CG9277, cel, Longterm, cell, Elektron, beta[[1]] tubulin, beta1t, T, beta-particle, Taf1p, Long-Term, Epigenomic, anon-EST:fe1B3, dTAF250, 1t, e, e-, beta1Tub, SPEC8, Long-Term Effect, CG5870, TAF, Long-Term Effects, beta-tubulin56D, Spec-beta, Dmbeta1, dTAF[[II]]230, TAF[[II]]250, BETA 56D, TAF200, Longterm Effect, Tubulin, l(3)84Ab, BG:DS00004.13, TAFII-250, i168, TAF250/230, Cell, Programs, dTAF230, TAFII250, l(1)G0108, microarray., p230, Long Term Effects, TAF[[II]]250/230, betaSpec, TFIID, FLOWERING TIME CONTROL PROTEIN FCA ALPHA, b-Spec, Taf[[II]]250, beta-tub, DmelCG5870, l(1)G0074, l(1)G0198, TAF[[II]]230, Beta <eudicots>, negatron, Epigenetic, beta[[1]]-tubulin, b spectrin, FCAALL.331, beta1, TAF[II]250, beta56D, DmelCG9277, CG17603, TAF[[II]], beta, Longterm Effects, beta1-tub, beta(-), DTB2, Tub, beta-Tub, DmelCG17603, Taf250, beta-spec, SR3-5, i6, DL4180C, BETA, Epigenetics, beta-Tub56D, time, Spec, betaTub, Specbeta, TAF230, beta1-Tubulin, TAF1mouse, mouse <Mus musculus>, house mouse.0.00.00.00.00.00falseMus musculusTranscriptional and epigenetic program changes of induced beta cells over time [expression array]2022-05-122014-11-15PRJNA255422GSE594902540261310090