Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single cell RNA-sequencing of esophageal epithelium from wild type and p63-KO mice

ABSTRACT: Cell fate determination and maintenance play critical roles in establishing and preserving tissue identity and function during organ development. Aberrant cell fate transitions can lead to cancer cells acquiring lineage plasticity, resulting in tumor heterogeneity and resistance to treatment. Trp63 (p63) is a transcription factor important for the formation of stratified squamous epithelium in the esophagus. Here, we report an unexpected role of p63 in protecting esophageal basal progenitor cells from committing to a neuroendocrine fate. Combination of single cell RNA sequencing analysis, lineage tracing and in vitro differentiation, we found that deletion of p63 in developing murine esophagus and in human embryonic stem cells results in extensive differentiation towards neuroendocrine lineage.

ORGANISM(S): Mus musculus

PROVIDER: GSE263694 | GEO | 2024/07/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy [RNAseq_ip63]

Project description:While cell fate determination and maintenance are important in establishing and preserving tissue identity and function during development, aberrant cell fate transition leads to cancer cell heterogeneity and resistance to treatment. Here, we report an unexpected role for the transcription factor p63 (Trp63/TP63) in the fate choice of squamous versus neuroendocrine lineage in esophageal development and malignancy. Deletion of p63 results in extensive neuroendocrine differentiation in the developing mouse esophagus and esophageal progenitors derived from human embryonic stem cells. In human esophageal neuroendocrine carcinoma (eNEC) cells, p63 is transcriptionally silenced by EZH2-mediated H3K27 trimethylation (H3K27me3). Upregulation of the major p63 isoform ΔNp63α, through either ectopic expression or EZH2 inhibition, promotes squamous transdifferentiation of eNEC cells. Together these findings uncover p63 as a rheostat in coordinating the transition between squamous and neuroendocrine cell fates during esophageal development and tumor progression.

2024-07-26 | GSE242463 | GEO

Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy [RNAseq_Ezh2i]

2024-07-26 | GSE242439 | GEO

Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy [RNAseq_Eso]

2024-07-26 | GSE242438 | GEO

Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy [CUTnTag_ip63]

2024-07-26 | GSE242437 | GEO

Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy [CUTnTag_Ezh2i]

2024-07-26 | GSE242436 | GEO

Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy [ChIP-seq]

2024-07-26 | GSE264639 | GEO

Gene expression profiles of p63 knockout mouse

Project description:p63 is essential for the self-renewal of stem cells of all stratified epithelial tissues, including mammary and prostate glands as well as all squamous epithelia. In p63 null embryos, stratified epithelial tissues are lost or eroded several days after stratification due to the loss of regenerative cell populations. Here we show that p63 null embryos rapidly develop intestine-like metaplasia with gene expression profiles similar to Barrett’s metaplasia in a proximal stomach region. Also, we found that deletion of p63 cells in bladder leads to an expansion of columnar epithelial cells along the basement membrane and their rapid transition to a metaplastic phenotype similar to Barrett’s esophagus. It is likely that bladder carcinogens recapitulate this entire metaplastic transition.

2024-06-30 | GSE65896 | GEO

Vitamin D Receptor Cross-talk with p63 Signaling Promotes Epidermal Cell Fate

Project description:The vitamin D receptor with its ligand 1,25 dihydroxy vitamin D3 (1,25D3) regulates epidermal stem cell fate, such that VDR removal from Krt14 expressing keratinocytes delays re-epithelialization of epidermis after wound injury in mice. In this study we deleted Vdr from Lrig1 expressing stem cells in the isthmus of the hair follicle then used lineage tracing to evaluate the impact on re-epithelialization following injury. We showed that Vdr deletion from these cells prevents their migration to and regeneration of the interfollicular epidermis without impairing their ability to repopulate the sebaceous gland. To pursue the molecular basis for these effects of VDR, we performed genome wide transcriptional analysis of keratinocytes from Vdr cKO and control littermate mice. Ingenuity Pathway analysis (IPA) pointed us to the TP53 family including p63 as a partner with VDR, a transcriptional factor that is essential for proliferation and differentiation of epidermal keratinocytes. Epigenetic studies on epidermal keratinocytes derived from interfollicular epidermis showed that VDR is colocalized with p63 within the specific regulatory region of MED1 containing super-enhancers of epidermal fate driven transcription factor genes such as Fos and Jun. Gene ontology analysis further implicated that Vdr and p63 associated genomic regions regulate genes involving stem cell fate and epidermal differentiation. To demonstrate the functional interaction between VDR and p63, we evaluated the response to 1,25(OH)2D3 of keratinocytes lacking p63 and noted a reduction in epidermal cell fate determining transcription factors such as Fos, Jun. We conclude that VDR is required for the epidermal stem cell fate orientation towards interfollicular epidermis following wounding. We propose that this role of VDR involves cross-talk with the epidermal master regulator p63 through super-enhancer mediated epigenetic dynamics.

2023-07-22 | GSE230578 | GEO

p63 regulates the switch from multipotency to unipotency during embryonic MG development

Project description:The mammary gland (MG) is composed of basal cells (BCs) and luminal cells (LCs). While it is generally believed that MG arises from embryonic multipotent progenitors (EMPs), it remains unclear when lineage restriction occurs and what are the mechanisms responsible for the switch from multipotency to unipotency during MG morphogenesis. Here, we performed multicolor lineage tracing and assessed the fate of single embryonic progenitors during mouse MG development. We demonstrated the existence of a developmental switch from multipotency to unipotency during embryonic MG development. Molecular profiling and single cell RNA-seq revealed the hybrid gene expression of EMPs, and the gene trajectory and lineage segregation occurring during MG development. In situ characterization showed that one of the earliest signs of lineage segregation consists in the restricted expression of p63 in the future BCs. Sustained p63 expression during MG development promotes unipotent BC fate in EMPs. Altogether, this study identifies the timing and the mechanisms mediating the switch from multipotency to unipotency during MG development. To understand the molecular mechanisms regulating multipotency during embryonic development, we isolated EMPs by FACS at E14, performed their transcriptional profiling by microarray and compared their transcriptome to adult BCs and LCs

2018-06-01 | GSE99433 | GEO

Pioneer and repressive functions of p63 during embryonic ectoderm specification [RNA-seq]

Project description:The transcription factor p63 is a master regulator of ectoderm development essential for epidermal specification. Although previous studies have highlighted the role of p63 triggering the epidermal transcriptomic program, its precise mechanism of target gene regulation in the complex context of a developing embryo remains poorly understood. Here, we used zebrafish embryos to analyze in vivo how p63 regulates the expression of its target genes during development. We generated tp63-knock-out mutants that recapitulate human phenotypes and show down-regulated epidermal gene expression. Following p63-binding dynamics during development, we found two distinct functions clearly separated in space and time. During early development, p63 binds enhancers associated to neural genes, where it limits Sox3 binding and reduces the expression of these neural genes. Indeed, we show that p63 and Sox3 are co-expressed in the neural plate border. Later in development, p63 binds enhancers associated to epidermal genes and promotes their expression, acting as a pioneer factor, as it binds to non-accessible chromatin and is required for its opening. Therefore, our results suggest that p63 is an important regulator of cell fate decisions during ectoderm specification, promoting the epidermal fate and inhibiting the neural program.

2019-06-06 | GSE123058 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data