Cardiac endothelial cells maintain open chromatin and expression of cardiomyocyte myofibrillar genes.
Cardiac endothelial cells maintain open chromatin and expression of cardiomyocyte myofibrillar genes.
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DOI：
10.7554/elife.55730
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发表时间：
2020-12-14
期刊：
影响因子：
7.7
通讯作者：
Arany Z
中科院分区：
文献类型：
--
作者：
Yucel N;Axsom J;Yang Y;Li L;Rhoades JH;Arany Z
内皮细胞（EC）是广泛的异质性，这取决于组织和血管定位。Jambusaria等人最近证明，各种组织中的EC令人惊讶地具有其底层薄壁组织的mRNA特征。这一观察结果的机制仍然无法解释，可能包括细胞分离过程中的mRNA污染，体内mRNA从实质细胞旁分泌转移到EC，或这些mRNA在EC中的细胞自主表达。在这里，我们使用批量RNASeq，单细胞RNASeq数据集，原位mRNA杂交，最重要的是FACS分离的细胞核的ATAC-Seq的组合，以显示心脏EC积极表达心肌细胞肌原纤维（CMF）基因，并在CMF基因启动子处具有开放的染色质。这些开放的染色质位点富含心脏转录因子靶向的位点，并在培养中EC扩增时关闭。总之，这些数据明确地表明，CMF基因在EC中的表达是细胞自主的，而不仅仅是技术污染或mRNA的旁分泌转移的结果，并表明心脏中的局部线索在体内出乎意料地保持EC中先前被认为仅限于心肌细胞的基因处的染色质完全开放。
Endothelial cells (ECs) are widely heterogenous depending on tissue and vascular localization. Jambusaria et al. recently demonstrated that ECs in various tissues surprisingly possess mRNA signatures of their underlying parenchyma. The mechanism underlying this observation remains unexplained, and could include mRNA contamination during cell isolation, in vivo mRNA paracrine transfer from parenchymal cells to ECs, or cell-autonomous expression of these mRNAs in ECs. Here, we use a combination of bulk RNASeq, single-cell RNASeq datasets, in situ mRNA hybridization, and most importantly ATAC-Seq of FACS-isolated nuclei, to show that cardiac ECs actively express cardiomyocyte myofibril (CMF) genes and have open chromatin at CMF gene promoters. These open chromatin sites are enriched for sites targeted by cardiac transcription factors, and closed upon expansion of ECs in culture. Together, these data demonstrate unambiguously that the expression of CMF genes in ECs is cell-autonomous, and not simply a result of technical contamination or paracrine transfers of mRNAs, and indicate that local cues in the heart in vivo unexpectedly maintain fully open chromatin in ECs at genes previously thought limited to cardiomyocytes.