Leveraging chromatin state transitions for regulatory networks identification in heart regeneration
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ABSTRACT:
PROVIDER: PRJNA871288 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21144517.fastq.gz | Fastqsanger.gz | |||
| SRR21144518.fastq.gz | Fastqsanger.gz | |||
| SRR21144519.fastq.gz | Fastqsanger.gz | |||
| SRR21144520.fastq.gz | Fastqsanger.gz | |||
| SRR21144521.fastq.gz | Fastqsanger.gz |
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Project description:Alterations that perturb differentiation and cell state transitions can lead to defects in development, function and the genesis of cancer. Studying cellular plasticity at high resolution and in real time has proven difficult using existing methods. Here, we use a quantitative approach to gain insights into cell state dynamics of normal mammary epithelial cells (MECs) and validate the model's predictions in vivo. In the absence of Slug/SNAI2, basal mammary progenitor cells transition into a luminal differentiation state, while luminal progenitor cells proliferate and expand; these changes result in abnormal mammary architecture and defects in tissue function. Loss of Slug also disrupts cellular plasticity leading to defects in tissue regeneration and the initiation of cancer. Mechanistically, Slug promotes cellular plasticity by recruiting the chromatin modifier, LSD1 (lysine specific demethylase 1), to promoters of lineage specific genes to represses transcription. Together, these finding demonstrate that Slug is necessary for cellular adaptation during tissue development and regeneration, and that transitioning back into a more primitive stem-like state is a prerequisite for tumor initiation.
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