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Integrated single-cell multiomics uncovers foundational regulatory mechanisms of lens development and pathology [Multiome snRNA/snATAC]

ABSTRACT: Integrated single-cell multiomics uncovers foundational regulatory mechanisms of lens development and pathology [Multiome snRNA/snATAC]

PROVIDER: PRJNA993023 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25212472_1.fastq.gz	Fastqsanger.gz
	SRR25212472_2.fastq.gz	Fastqsanger.gz
	SRR25212473_1.fastq.gz	Fastqsanger.gz
	SRR25212473_2.fastq.gz	Fastqsanger.gz
	SRR25212474_1.fastq.gz	Fastqsanger.gz

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Integrated single-cell multiomics uncovers foundational regulatory mechanisms of lens development and pathology [Multiome snRNA/snATAC]

Project description:Ocular lens development entails epithelial to fiber cell differentiation, defects in which cause congenital cataract. We report the first single-cell multiomic atlas of lens development, leveraging snRNA-seq, snATAC-seq, and CUT&RUN-seq to discover novel mechanisms of cell fate determination and cataract-linked regulatory networks. A comprehensive profile of cis- and trans-regulatory interactions, including for the cataract-linked transcription factor MAF, is established across a temporal trajectory of fiber cell differentiation. Further, we divulge a conserved epigenetic paradigm of cellular differentiation, defined by progressive loss of H3K27 methylation writer Polycomb repressive complex 2 (PRC2). PRC2 localizes to heterochromatin domains across master-regulator transcription factor gene bodies, suggesting it safeguards epithelial cell fate. Moreover, we demonstrate that FGF hyper-stimulation in vivo leads to MAF network activation and the emergence of novel lens cell states. Collectively, these data depict a comprehensive portrait of lens fiber cell differentiation, while defining regulatory effectors of cell identity and cataract formation.

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Project description:Integrated single-cell multiomics uncovers foundational regulatory mechanisms of lens development and pathology [CUT&RUN]

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