Dynamics of Chromatin Accessibility during Hematopoietic Stem Cell Differentiation into Lineage-Committed Progeny
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ABSTRACT:
PROVIDER: PRJNA766652 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16089276_1.fastq.gz | Fastqsanger.gz | |||
| SRR16089276_2.fastq.gz | Fastqsanger.gz | |||
| SRR16089277_1.fastq.gz | Fastqsanger.gz | |||
| SRR16089277_2.fastq.gz | Fastqsanger.gz | |||
| SRR16089278_1.fastq.gz | Fastqsanger.gz |
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Project description:Epigenetic mechanisms regulate the multilineage differentiation capacity of hematopoietic stem cells (HSCs) into a variety of blood and immune cells. Our recent work revealed evidence of multilineage gene priming in HSCs, where open cis-regulatory elements (CREs) exclusively shared between HSCs and unipotent lineage cells were enriched for DNA binding motifs of known lineage-specific transcription factors. To test the hypothesis that HSC-primed lineage-specific CREs remain accessible throughout differentiation, we used ATAC-seq to map the temporal dynamics of chromatin remodeling during blood cell differentiation. We observed epigenetic-driven clustering of oligopotent and unipotent progenitors into distinct erythromyeloid and lymphoid branches, with multipotent HSCs and MPPs associating with the erythromyeloid lineage. We mapped the dynamics of lineage-primed CREs throughout hematopoiesis and identified both unique and shared CREs as potential lineage reinforcement mechanisms at fate branch points in hematopoiesis. These findings provide insight into the regulation of stem cell multipotency and lineage commitment throughout hematopoiesis and serve as a resource to test functional drivers of hematopoietic lineage fate.
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Project description:Hematopoietic stem cells (HSC) possess life-long self-renewal activity and generate a series of multipotent progenitors that differentiate into lineage-committed progenitors and subsequently mature cells. Recently, functionally distinct stem and progenitor cell types have been identified, however, a systems-wide understanding of the underlying gene regulation is lacking. Here, we present the global transcriptome of ex vivo isolated mouse multipotent hematopoietic stem cells (HSC) and multipotent progenitor cells (MPP1-MPP4) as revealed by next-generation sequencing (RNA-seq). A related high-throughput study with DNA methylome data was also conducted, with data deposited at NCBI Gene Expression Omnibus, under accession GSE52709 ( http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52709 ). An imported copy of the methylome data set can also be found at ArrayExpress: http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-52709.
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