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Histone variant H2AFV expression defines functionally distinct cancer subpopulations [RNA-seq]

ABSTRACT: Histone variant H2AFV expression defines functionally distinct cancer subpopulations [RNA-seq]

PROVIDER: PRJNA640659 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12056011_1.fastq.gz	Fastqsanger.gz
	SRR12056011_2.fastq.gz	Fastqsanger.gz
	SRR12056012_1.fastq.gz	Fastqsanger.gz
	SRR12056012_2.fastq.gz	Fastqsanger.gz
	SRR12056013_1.fastq.gz	Fastqsanger.gz

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Histone variant H2AFV expression defines functionally distinct cancer subpopulations [RNA-seq]

Project description:Tumors are composed of cellular subpopulations with varying degree of proliferative and tumorigenic potential. Here, we identify inter- and intra-tumor heterogeneous expression of histone variant H2AFV in numerous cancer types, with high H2AFV expression correlating with cancer stem cells, poorly differentiated tumors and inferior patient survival. Depletion of H2AFV impairs proliferation, invasiveness, tumorigenicity and tumor initiating cell frequency of glioblastoma. Mechanistically, H2AFV regulates chromatin accessibility of both active and repressive complexes at the promoters and enhancers of genes: the former activates genes involved in cell proliferation/self-renewal and invasiveness while the latter suppresses cellular differentiation in cancer stem cells. Our studies uncover H2AFV as an important epigenetic determinant in cancer stem cell fate and a significant contributor of intratumor heterogeneity.

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Quorum sensing elicits functionally distinct subpopulations of infectious Legionella

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Spatial and single-cell transcriptional profiling identifies functionally distinct human dermal fibroblast subpopulations

Project description:Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining tissue integrity. We have previously shown that mouse skin connective tissue, the dermis, is comprised of functionally distinct fibroblast lineages. However, the extent of fibroblast heterogeneity in human skin is unknown. Here, using a combination of spatial transcriptional profiling of human and mouse dermis and single cell transcriptional profiling of human dermal fibroblasts, we show that there are at least four distinct fibroblast populations in adult human skin. We define markers permitting prospective isolation of these cells and show that although marker expression is rapidly lost in culture, different fibroblast subpopulations retain distinct functionality in terms of Wnt signalling, T cell communication and the ability to support human epidermal reconstitution in organotypic culture. Furthermore, while some fibroblast subpopulations are spatially segregated, others are not. These findings have profound implications for normal wound healing and diseases characterized by excessive fibrosis, and suggest that ex vivo expansion or in vivo ablation of specific fibroblast subpopulations may have therapeutic applications.

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Spatial and single-cell transcriptional profiling identifies functionally distinct human dermal fibroblast subpopulations

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Functionally Distinct Subpopulations of CpG-Activated Memory B Cells.

Project description:During the human B cell (Bc) recall response, rapid cell division results in multiple Bc subpopulations. The TLR-9 agonist CpG oligodeoxynucleotide, combined with cytokines, causes Bc activation and division in vitro and increased CD27 surface expression in a sub-population of Bc. We hypothesized that the proliferating CD27(lo) subpopulation, which has a lower frequency of antibody-secreting cells (ASC) than CD27(hi) plasmablasts, provides alternative functions such as cytokine secretion, costimulation, or antigen presentation. We performed genome-wide transcriptional analysis of CpG activated Bc sorted into undivided, proliferating CD27(lo) and proliferating CD27(hi) subpopulations. Our data supported an alternative hypothesis, that CD27(lo) cells are a transient pre-plasmablast population, expressing genes associated with Bc receptor editing. Undivided cells had an active transcriptional program of non-ASC B cell functions, including cytokine secretion and costimulation, suggesting a link between innate and adaptive Bc responses. Transcriptome analysis suggested a gene regulatory network for CD27(lo) and CD27(hi) Bc differentiation.

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