Chromatin accessibility maps provide evidence of multilineage gene priming in hematopoietic stem cells.

Chromatin accessibility maps provide evidence of multilineage gene priming in hematopoietic stem cells.
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DOI:
10.1186/s13072-020-00377-1
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发表时间:
2021-01-06
影响因子:
3.9
通讯作者:
Forsberg EC
Forsberg EC
中科院分区:
生物学2区
文献类型:
--
作者:
Martin EW;Krietsch J;Reggiardo RE;Sousae R;Kim DH;Forsberg EC

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造血干细胞(HSC)具有分化成不同类型的成熟血细胞的能力。调控HSC多谱系能力或多能性的表观遗传机制还不清楚。为了检验控制所有谱系命运决定的顺式调节元件在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。我们观察到巨核祖细胞和HSC之间的可及性特征的最高相似性,而B细胞在分化过程中具有最多的从头获得可及性的区域。尽管有这些差异,我们确定了顺式调控元件从所有的谱系,显示表观遗传引发的HSC。这些发现为干细胞多能性的调控提供了新的见解,也为识别谱系命运的功能驱动因素提供了资源。
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.
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