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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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Project description:Astrocytes execute a diverse range of tasks that facilitate brain physiology, raising the possibility that these diverse astrocytic roles are enabled by functionally distinct subtypes1,2. Recent studies identified molecular diversity amongst astrocytes3, however whether this molecular heterogeneity reflects specialized astrocyte subpopulations with distinct functions remains unknown. Leveraging prior molecular and functional studies4, we generated a CD51-FLP mouse line that enables the direct comparison of functional properties between CD51+ and CD51- astrocyte subpopulations in neural circuits in vivo. Here we show that CD51+ and CD51- astrocytes are endowed with unique morphological, physiological, and developmental properties in both the cortex and hippocampus. Functional studies demonstrate that CD51+ astrocytes selectively promote synapse formation in the developing cortex and circuit plasticity in the hippocampus. Mechanistically, we found that CD51+ astrocytes function through glypican 6 to promote synapse formation in the cortex, while CD51 itself drives circuit plasticity in the hippocampus. Applying these findings to brain injury, we found that exploiting the unique properties of CD51+ astrocytes promotes functional recovery after stroke through enhanced synaptic remodeling. Taken together, our studies identify specialized astrocyte subpopulations that exhibit distinct functional properties in the developing, mature, and injured brain.

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

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