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RNA sequencing of MMTV-Neu early lesion (EL) and primary tumor (PT) spheres

ABSTRACT: Cancer cells can disseminate from early-evolved primary lesions. It is thought that a state of early disseminated cancer cell (early DCC) dormancy would precede genetic maturation of DCCs and metastasis initiation. Here we reveal at single cell resolution a previously unrecognized role of mesenchymal- and pluripotency-like programs in coordinating early cancer cell spread and a long-lived dormancy program in early DCCs. We identify in early lesions and early DCCs, the transcription factor ZFP281 as an inducer of mesenchymal- and primed pluripotency-like programs, which is absent in advanced primary tumors and overt metastasis. ZFP281 not only controls the early spread of cancer cells but also locks early DCCs in a prolonged dormancy state by preventing the acquisition of an epithelial-like proliferative program. Thus, ZFP281-driven dormancy of early DCCs may be a rate-limiting step in metastatic progression functioning as a first barrier that DCCs must overcome to then undergo genetic maturation.

ORGANISM(S): Mus musculus

PROVIDER: GSE165431 | GEO | 2021/01/26

REPOSITORIES: GEO

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ZFP281 ChIP-sequencing of MMTV-Neu early lesion (EL) and primary tumor (PT) spheres

Project description:Cancer cells can disseminate from early-evolved primary lesions. It is thought that a state of early disseminated cancer cell (early DCC) dormancy would precede genetic maturation of DCCs and metastasis initiation. Here we reveal at single cell resolution a previously unrecognized role of mesenchymal- and pluripotency-like programs in coordinating early cancer cell spread and a long-lived dormancy program in early DCCs. We identify in early lesions and early DCCs, the transcription factor ZFP281 as an inducer of mesenchymal- and primed pluripotency-like programs, which is absent in advanced primary tumors and overt metastasis. ZFP281 not only controls the early spread of cancer cells but also locks early DCCs in a prolonged dormancy state by preventing the acquisition of an epithelial-like proliferative program. Thus, ZFP281-driven dormancy of early DCCs may be a rate-limiting step in metastatic progression functioning as a first barrier that DCCs must overcome to then undergo genetic maturation. This data set aims identify ZFP281 targets in MMTV-Neu early lesion (EL) and primary tumor (PT) cells

2021-01-26 | GSE165444 | GEO

scRNAseq of MMTV-Neu lung cancer cells in early and late stage

Project description:Cancer cells can disseminate from early-evolved primary lesions. It is thought that a state of early disseminated cancer cell (early DCC) dormancy would precede genetic maturation of DCCs and metastasis initiation. Here we reveal at single cell resolution a previously unrecognized role of mesenchymal- and pluripotency-like programs in coordinating early cancer cell spread and a long-lived dormancy program in early DCCs. We identify in early lesions and early DCCs, the transcription factor ZFP281 as an inducer of mesenchymal- and primed pluripotency-like programs, which is absent in advanced primary tumors and overt metastasis. ZFP281 not only controls the early spread of cancer cells but also locks early DCCs in a prolonged dormancy state by preventing the acquisition of an epithelial-like proliferative program. Thus, ZFP281-driven dormancy of early DCCs may be a rate-limiting step in metastatic progression functioning as a first barrier that DCCs must overcome to then undergo genetic maturation. This data set aims to characterize MMTV-Neu early and late lung disseminated cancer cells (DCCs).

2021-01-26 | GSE165459 | GEO

scRNAseq of MMTV-Neu primary site and lung cancer cells in early and late stage

Project description:Cancer cells can disseminate from early-evolved primary lesions. It is thought that a state of early disseminated cancer cell (early DCC) dormancy would precede genetic maturation of DCCs and metastasis initiation. Here we reveal at single cell resolution a previously unrecognized role of mesenchymal- and pluripotency-like programs in coordinating early cancer cell spread and a long-lived dormancy program in early DCCs. We identify in early lesions and early DCCs, the transcription factor ZFP281 as an inducer of mesenchymal- and primed pluripotency-like programs, which is absent in advanced primary tumors and overt metastasis. ZFP281 not only controls the early spread of cancer cells but also locks early DCCs in a prolonged dormancy state by preventing the acquisition of an epithelial-like proliferative program. Thus, ZFP281-driven dormancy of early DCCs may be a rate-limiting step in metastatic progression functioning as a first barrier that DCCs must overcome to then undergo genetic maturation. This data set aims for a general characterization of the MMTV-Neu mouse model (primary site and lung DCCs) in early and late stages of cancer progression.

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The pluripotency factor Zfp281 coordinates transcriptional and epigenetic control of epiblast maturation [RNA-seq]

Project description:The early development of mouse embryos involves a tightly regulated series of lineage specification events. Following implantation, these events include maturation of the pluripotent epiblast and simultaneous establishment of the embryonic axes. Here we report that Zfp281, a transcription factor shown to be required for transitioning cells in culture from naïve to primed states of pluripotency, is essential for mouse embryonic development by regulating epiblast maturation. Transcriptomic analyses of Zfp281 mutant embryos revealed a failure in activating Nodal signaling in the epiblast leading to failure in establishing the anterior-posterior axis, and impaired epiblast maturation. Our study establishes Zfp281 as a critical factor that coordinates transcriptional and epigenetic control of pluripotent epiblast maturation.

2017-11-24 | GSE93043 | GEO

The pluripotency factor Zfp281 coordinates transcriptional and epigenetic control of epiblast maturation [ChIP-seq]

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Project description:For the first time in melanoma, novel therapies have recently shown efficacy in the adjuvant therapy setting, which makes companion diagnostics to guide treatment decisions a desideratum. Early spread of disseminated cancer cells (DCC) to sentinel lymph nodes (SLN) is indicative of poor prognosis in melanoma and early DCCs could therefore provide important information about the malignant seed. Here, we present a strategy for enrichment of DCCs from SLN suspensions using a microfluidic device (ParsortixTM, Angle plc). This approach enables the detection and isolation of viable DCCs, followed by molecular analysis and identification of genetic changes. By optimizing the workflow, the established protocol allows a high recovery of DCC from melanoma patient-derived LN suspensions with harvest rates above 60%. We then assessed the integrity of the transcriptome and genome of individual, isolated DCCs. In LNs of melanoma patients, we detected the expression of melanoma-associated transcripts including MLANA (encoding for MelanA protein), analysed the BRAF and NRAS mutational status and confirmed the malignant origin of isolated melanoma DCCs by comparative genomic hybridization. We demonstrate the feasibility of epitope-independent isolation of LN DCCs using ParsortixTM for subsequent molecular characterization of isolated single DCCs with ample application fields including the use for companion diagnostics or subsequent cellular studies in personalized medicine.

2018-08-14 | GSE118478 | GEO

Zfp281 Coordinates Opposite Functions of Tet1 and Tet2 for Alternative Pluripotent States [RNA-Seq]

Project description:Pluripotent cell identity comprises a spectrum of cell states including naive and primed states, which are typified by mouse embryonic stem cells (ESCs) and epiblast-derived stem cells (EpiSCs), respectively. Here we define a pluripotent cell fate (PCF) gene signature based on RNA-seq analysis associated with naive and primed pluripotency acquisition, and identify Zfp281 as a key transcriptional regulator for primed pluripotency and also as a barrier to achieve the naive pluripotency of both mouse and human ESCs. RNA sequencing analysis was performed in WT and Zfp281 null mouse embryonic stem cells under different pluripotent culture conditions. RNA-seq Experiments were carry out in two biological replciates. Genome binding/occupancy profiling of Zfp281 was performed in mouse embryonic stem cells by ChIP sequencing.

2016-06-28 | E-GEOD-81044 | biostudies-arrayexpress

Zfp281 Coordinates Opposite Functions of Tet1 and Tet2 for Alternative Pluripotent States [ChIP-Seq]

2016-06-28 | E-GEOD-81042 | biostudies-arrayexpress

The pluripotency factor Zfp281 coordinates transcriptional and epigenetic control of epiblast maturation

Project description:The pluripotency factor Zfp281 coordinates transcriptional and epigenetic control of epiblast maturation

| PRJNA359643 | ENA

Methylation Changes During Soybean Seed Development

Project description:What methylation changes are occurring during seed development largely remains unknown. To uncover the possible role of DNA methylation during the transition from seed differentiation to maturation and dormany in soybean, we characterized the methylome of whole seeds representing the differentiation (GLOB stage), maturation (early- (EM), mid- (B1) and late- (AA1) maturation stages), and dormancy (DRY stage) phases of soybean seed development using Illumina sequencing. In addition, we characterized the methylome of the mid-maturation stage embryonic axis (B1-AX) to examine methylation differences, if any, between an embryonic region compared to the whole seed. Illumina sequencing of bisulfite-converted genomic DNA from globular stage (GLOB), early-maturation stage (EM), mid-maturation stage (B1), and late-maturation stage (AA1) seeds, dormancy stage (DRY) and mid-maturation embryonic axis (B1-AX).

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