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Polycomb Repressive Complex 2 regulates basal cell fate during adult olfactory neurogenesism [scRNA-seq]

ABSTRACT: Polycomb Repressive Complex 2 regulates basal cell fate during adult olfactory neurogenesism [scRNA-seq]

PROVIDER: PRJNA934551 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23379500.fastq.gz	Fastqsanger.gz
	SRR23379501.fastq.gz	Fastqsanger.gz
	SRR23379502.fastq.gz	Fastqsanger.gz
	SRR23379503.fastq.gz	Fastqsanger.gz
	SRR23379496.fastq.gz	Fastqsanger.gz

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Polycomb Repressive Complex 2 regulates basal cell fate during adult olfactory neurogenesis [EEDKO_H3K27me3_ChIP]

Project description:We show that Polycomb repressive complexes (PRCs) regulate lineage choice between neural and non-neural fates in the olfactory epithelium. Conditional loss of Polycomb repressive complex 2 perturbs lesion-induced neurogenesis and misexpression of lineage-specific transcription factors in multipotent olfactory globose basal cells.

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Polycomb Repressive Complex 2 regulates basal cell fate during adult olfactory neurogenesism [scRNA-seq]

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Polycomb Repressive Complex 2 regulates basal cell fate during adult olfactory neurogenesis

Project description:Polycomb Repressive Complex 2 regulates basal cell fate during adult olfactory neurogenesis

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Polycomb Repressive Complex 2 regulates basal cell fate during adult olfactory neurogenesis [EEDKO_H3K27me3_ChIP]

Project description:Polycomb Repressive Complex 2 regulates basal cell fate during adult olfactory neurogenesis [EEDKO_H3K27me3_ChIP]

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Polycomb Repressive Complex 2 regulates basal cell fate during adult olfactory neurogenesis [ChIP-seq]

Project description:Polycomb Repressive Complex 2 regulates basal cell fate during adult olfactory neurogenesis [ChIP-seq]

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Polycomb repressive complex 2 regulates basal cell fate during adult olfactory neurogenesis.

Project description:Adult neurogenesis occurs in the mammalian olfactory epithelium to maintain populations of neurons that are vulnerable to injury yet essential for olfaction. Multipotent olfactory basal stem cells are activated by damage, although mechanisms regulating lineage decisions are not understood. Using mouse lesion models, we focused on defining the role of Polycomb repressive complexes (PRCs) in olfactory neurogenesis. PRC2 has a well-established role in developing tissues, orchestrating transcriptional programs via chromatin modification. PRC2 proteins are expressed in olfactory globose basal cells (GBCs) and nascent neurons. Conditional PRC2 loss perturbs lesion-induced neuron production, accompanied by altered histone modifications and misexpression of lineage-specific transcription factors in GBCs. De-repression of Sox9 in PRC2-mutant GBCs is accompanied by increased Bowman's gland production, defining an unrecognized role for PRC2 in regulating gland versus neuron cell fate. Our findings support a model for PRC2-dependent mechanisms promoting sensory neuronal differentiation in an adult neurogenic niche.

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Polycomb Repressive Complex 2 Restricts Human Naive Pluripotent Stem Cell to Trophoblast Fate Induction

Project description:Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested. Here, we apply multi-omics to comprehensively define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Integrating the chromatin-bound proteome and histone modification data sets reveals differences in the relative abundance and activities of distinct chromatin modules, identifying a strong enrichment of Polycomb Repressive Complex 2 (PRC2)-associated H3K27me3 in naive pluripotent stem cell chromatin. Single-cell approaches and human blastoid models reveal that PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, and inhibiting PRC2 promotes trophoblast fate induction and cavity formation. Our results establish that human naive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose the induction of alternative cell fates.

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Project description:Polycomb proteins assemble to form complexes with important roles in epigenetic regulation. The Polycomb Repressive Complex 2 (PRC2) modulates the di- and tri-methylation of lysine 27 on histone H3, each of which are associated with gene repression. Although three subunits, EZH1/2, SUZ12 and EED, form the catalytic core of PRC2, a wider group of proteins associate with low stoichiometry. This raises the question of whether dynamic variation of the PRC2 interactome results in alternative forms of the complex during differentiation. Here we compared the physical interactions of PRC2 in undifferentiated and differentiated states of NTERA2 pluripotent embryonic carcinoma cells. Label-free quantitative proteomics was used to assess endogenous immunoprecipitation of the EZH2 and SUZ12 subunits of PRC2. A high stringency dataset reflecting the endogenous state of PRC2 was produced that included all previously reported ‘core’ and ‘associated’ PRC2 components, and several novel interacting proteins. Comparison of the interactomes obtained in undifferentiated and differentiated cells revealed candidate proteins that favoured either one or other state. For example, SALL4 and ZNF281 associate with PRC2 in pluripotent cells, while PCL1 and SMAD3 more associate with PRC2 in differentiating cells. Analysis of the mRNA and protein levels of these factors found that their association with PRC2 correlated with their cell state-specific expression. Taken together, we propose that dynamic changes to the PRC2 interactome during differentiation may contribute to directing its activity during cell fate transitions.

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