小柯机器人

造血过程的染色质动力学获揭示
2022-12-21 20:36

荷兰Oncode研究所Alexander van Oudenaarden小组取得一项新突破。他们利用单细胞sortChIC揭示了造血过程的染色质动力学。2022年12月20日出版的《自然-遗传学》杂志发表了这项成果。

研究人员开发了分选辅助单细胞染色质免疫切割(sortChIC),并在小鼠骨髓中绘制了激活性(H3K4me1和H3K4me3)和抑制性(H3K27me3和H3K9me3)组蛋白修饰。在分化过程中,造血干细胞和祖细胞(HSPC)具有细胞类型特异性转录因子介导的活性染色质状态,这些转录因子对于每个谱系都是唯一的。相比之下,分化过程中大多数抑制性标记的改变与最终细胞类型无关。

染色质轨迹分析表明,染色质水平的谱系选择发生在祖细胞阶段。H3K4me1和H3K9me3的联合分析表明,骨髓来源的细胞类型具有不同的活性染色质,但具有相似的髓系特异性异染色质状态。这意味着造血过程中存在染色质的分层调节:异染色质动力学区分分化轨迹和谱系,而常染色质动力学反映谱系内的细胞类型。

研究人员表示,组蛋白翻译后修饰通过改变染色质活性来影响基因表达。尚不清楚染色质状态如何影响单细胞谱系选择的机制。

附:英文原文

Title: Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis

Author: Zeller, Peter, Yeung, Jake, Vias Gaza, Helena, de Barbanson, Buys Anton, Bhardwaj, Vivek, Florescu, Maria, van der Linden, Reinier, van Oudenaarden, Alexander

Issue&Volume: 2022-12-20

Abstract: Post-translational histone modifications modulate chromatin activity to affect gene expression. How chromatin states underlie lineage choice in single cells is relatively unexplored. We develop sort-assisted single-cell chromatin immunocleavage (sortChIC) and map active (H3K4me1 and H3K4me3) and repressive (H3K27me3 and H3K9me3) histone modifications in the mouse bone marrow. During differentiation, hematopoietic stem and progenitor cells (HSPCs) acquire active chromatin states mediated by cell-type-specifying transcription factors, which are unique for each lineage. By contrast, most alterations in repressive marks during differentiation occur independent of the final cell type. Chromatin trajectory analysis shows that lineage choice at the chromatin level occurs at the progenitor stage. Joint profiling of H3K4me1 and H3K9me3 demonstrates that cell types within the myeloid lineage have distinct active chromatin but share similar myeloid-specific heterochromatin states. This implies a hierarchical regulation of chromatin during hematopoiesis: heterochromatin dynamics distinguish differentiation trajectories and lineages, while euchromatin dynamics reflect cell types within lineages.

DOI: 10.1038/s41588-022-01260-3

Source: https://www.nature.com/articles/s41588-022-01260-3

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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