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Chromatin accessibility maps provide evidence of multilineage gene priming in hematopoietic stem cells
Epigenetics & Chromatin ( IF 4.2 ) Pub Date : 2021-01-06 , DOI: 10.1186/s13072-020-00377-1
Eric W Martin 1 , Jana Krietsch 1 , Roman E Reggiardo 1 , Rebekah Sousae 1 , Daniel H Kim 1 , E Camilla Forsberg 1
Affiliation  

Hematopoietic stem cells (HSCs) have the capacity to differentiate into vastly different types of mature blood cells. The epigenetic mechanisms regulating the multilineage ability, or multipotency, of HSCs are not well understood. To test the hypothesis that cis-regulatory elements that control fate decisions for all lineages are primed in HSCs, we used ATAC-seq to compare chromatin accessibility of HSCs with five unipotent cell types. We observed the highest similarity in accessibility profiles between megakaryocyte progenitors and HSCs, whereas B cells had the greatest number of regions with de novo gain in accessibility during differentiation. Despite these differences, we identified cis-regulatory elements from all lineages that displayed epigenetic priming in HSCs. These findings provide new insights into the regulation of stem cell multipotency, as well as a resource to identify functional drivers of lineage fate.

中文翻译:


染色质可及性图谱提供了造血干细胞中多谱系基因启动的证据



造血干细胞 (HSC) 具有分化成截然不同类型的成熟血细胞的能力。调节 HSC 的多谱系能力或多能性的表观遗传机制尚不清楚。为了检验控制所有谱系命运决定的顺式调控元件在 HSC 中启动的假设,我们使用 ATAC-seq 比较了 HSC 与五种单能细胞类型的染色质可及性。我们观察到巨核细胞祖细胞和 HSC 之间的可及性概况具有最高的相似性,而 B 细胞在分化过程中具有最大数量的可及性从头获得的区域。尽管存在这些差异,我们还是从所有在 HSC 中表现出表观遗传启动的谱系中鉴定出了顺式调控元件。这些发现为干细胞多能性的调节提供了新的见解,并为识别谱系命运的功能驱动因素提供了资源。
更新日期:2021-01-07
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