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Epigenomic analyses of FOXA1-mediated enhancer reprogramming to control tumor subtype plasticity through HH-BMP-FOXA1 signalling feedback between urothelial tumor and stromal fibroblasts

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE141356 | GEO | 2020/09/27

REPOSITORIES: GEO

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Epigenomic analyses of FOXA1-mediated enhancer reprogramming to control tumor subtype plasticity through HH-BMP-FOXA1 signalling feedback between urothelial tumor and stromal fibroblasts [FOXA1 ChIP-seq]

Project description:Consistent with the previous study, we showed that tumor molecular subtypes switched between the luminal subtype and the basal subtype during long-term maintenance of conventional tumor organoids in the absence of stroma in vitro, indicating the important role of tumor stroma in maintaining the tumor phenotype. Interestingly, genomic alterations seen in parental tumors are preserved well in both conventional tumor organoids and tumor assembloids, implying that the determination of tumor phenotypes may rely on epigenetic changes in tumor stroma-dependent ways, particularly through stromal BMP signals, elicited by Hh expression in tumor cells. We performed extensive epigenomic analyses including RNA-seq, ATAC-seq, and ChIP-seq with genetically manipulated tumor assembloids, in which genetic manipulations were applied independently to tumor organoids and tumor stroma in a combinatorial manner. Using this system, we identified FOXA1 as a master pioneering factor that drives enhancer reprogramming during the molecular switching of tumor subtypes. We have also obtained new evidence that FOXA1 is induced by stromal BMP signals and identified the HH-BMP-FOXA1 signaling feedback between urothelial tumors and stromal fibroblasts as a critical signaling axis in the FOXA1-mediated enhancer reprogramming of tumor phenotypes in the determination of urothelial carcinomas.

2020-09-27 | GSE141354 | GEO

Epigenomic analyses of FOXA1-mediated enhancer reprogramming to control tumor subtype plasticity through HH-BMP-FOXA1 signalling feedback between urothelial tumor and stromal fibroblasts [ATAC-seq]

2020-09-27 | GSE141351 | GEO

Epigenomic analyses of FOXA1-mediated enhancer reprogramming to control tumor subtype plasticity through HH-BMP-FOXA1 signalling feedback between urothelial tumor and stromal fibroblasts [RNA-seq]

2020-09-27 | GSE141350 | GEO

2020-09-27 | GSE148819 | GEO

Epigenomic analyses of FOXA1-mediated enhancer reprogramming to control tumor subtype plasticity through HH-BMP-FOXA1 signalling feedback between urothelial tumor and stromal fibroblasts

Project description:Epigenomic analyses of FOXA1-mediated enhancer reprogramming to control tumor subtype plasticity through HH-BMP-FOXA1 signalling feedback between urothelial tumor and stromal fibroblasts

| PRJNA593207 | ENA

| PRJNA593210 | ENA

Epigenomic analyses of FOXA1-mediated enhancer reprogramming to control tumor subtype plasticity through HH-BMP-FOXA1 signalling feedback between urothelial tumor and stromal fibroblasts [RNA-seq]

| PRJNA593203 | ENA

Epigenomic analyses of FOXA1-mediated enhancer reprogramming to control tumor subtype plasticity through HH-BMP-FOXA1 signalling feedback between urothelial tumor and stromal fibroblasts [ATAC-seq]

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Temporal control of BMP signalling determines neuronal subtype identity in the dorsal neural tube.

Project description:The conventional explanation for how a morphogen patterns a tissue holds that cells interpret different concentrations of an extrinsic ligand by producing corresponding levels of intracellular signalling activity, which in turn regulate differential gene expression. However, this view has been challenged, raising the possibility that distinct mechanisms are used to interpret different morphogens. Here, we investigate graded BMP signalling in the vertebrate neural tube. We show that defined exposure times to Bmp4 generate distinct levels of signalling and induce specific dorsal identities. Moreover, we provide evidence that a dynamic gradient of BMP activity confers progressively more dorsal neural identities in vivo. These results highlight a strategy for morphogen interpretation in which the tight temporal control of signalling is important for the spatial pattern of cellular differentiation.

| S-EPMC3596990 | biostudies-literature

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