Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California, 1156 High Street, Santa Cruz, CA, 95064, USA.
Epigenetics Chromatin. 2021 Jan 6;14(1):2. doi: 10.1186/s13072-020-00377-1.
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.
造血干细胞（HSCs）具有分化为多种成熟血细胞的能力。调节 HSCs 多谱系能力或多能性的表观遗传机制尚不清楚。为了检验这样一个假设，即控制所有谱系命运决定的顺式调控元件在 HSCs 中被预先设定，我们使用 ATAC-seq 比较了 HSCs 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 HSCs 之间的可及性图谱最相似，而 B 细胞在分化过程中具有最多数量的新获得可及性的区域。尽管存在这些差异，我们还是从所有谱系中鉴定出了在 HSCs 中表现出表观遗传预先设定的顺式调控元件。这些发现为干细胞多能性的调控提供了新的见解，也为鉴定谱系命运的功能驱动因素提供了资源。
