小柯机器人

以色列耶路撒冷希伯来大学Nir Friedman研究团队在研究中取得进展。他们利用针对血浆无细胞核小体的ChIP-seq鉴定了细胞来源的基因表达基序。相关论文于2021年1月11日发表于《自然-生物技术》杂志。

在本研究中，研究人员利用染色质免疫沉淀检测了无细胞核小体中活性染色质的修饰，并对268个人类样品进行了测序（cfChIP-seq）。在健康供体中，研究人员发现骨髓巨核细胞而非成熟红细胞是无细胞DNA（cfDNA）库的主要来源。在患有一系列肝脏疾病的患者中，研究人员证明了其可以识别肝细胞转录过程中与病理相关的变化。在转移性大肠癌患者中，研究人员检测到了与临床相关和患者特定的信息，包括转录活性人表皮生长因子受体2（HER2）的扩增。

总而言之，cfChIP-seq使用较低的测序深度，可提供系统的全基因组信息，并且可以提供诊断信息，有助于使用血样进行生理和病理过程的追溯。

研究人员表示，人血浆中的cfDNA可提供有关器官或肿瘤病理起始过程的分子信息。这些DNA来自于死细胞中的染色质片段，并保留了一些来源细胞的组蛋白修饰。

附：英文原文

Title: ChIP-seq of plasma cell-free nucleosomes identifies gene expression programs of the cells of origin

Author: Ronen Sadeh, Israa Sharkia, Gavriel Fialkoff, Ayelet Rahat, Jenia Gutin, Alon Chappleboim, Mor Nitzan, Ilana Fox-Fisher, Daniel Neiman, Guy Meler, Zahala Kamari, Dayana Yaish, Tamar Peretz, Ayala Hubert, Jonathan E. Cohen, Azzam Salah, Mark Temper, Albert Grinshpun, Myriam Maoz, Samir Abu-Gazala, Ami Ben Yaacov, Eyal Shteyer, Rifaat Safadi, Tommy Kaplan, Ruth Shemer, David Planer, Eithan Galun, Benjamin Glaser, Aviad Zick, Yuval Dor, Nir Friedman

Issue&Volume: 2021-01-11

Abstract: Cell-free DNA (cfDNA) in human plasma provides access to molecular information about the pathological processes in the organs or tumors from which it originates. These DNA fragments are derived from fragmented chromatin in dying cells and retain some of the cell-of-origin histone modifications. In this study, we applied chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin modifications followed by sequencing (cfChIP-seq) to 268 human samples. In healthy donors, we identified bone marrow megakaryocytes, but not erythroblasts, as major contributors to the cfDNA pool. In patients with a range of liver diseases, we showed that we can identify pathology-related changes in hepatocyte transcriptional programs. In patients with metastatic colorectal carcinoma, we detected clinically relevant and patient-specific information, including transcriptionally active human epidermal growth factor receptor 2 (HER2) amplifications. Altogether, cfChIP-seq, using low sequencing depth, provides systemic and genome-wide information and can inform diagnosis and facilitate interrogation of physiological and pathological processes using blood samples. Circulating cell-free DNA from patients is analyzed by ChIP-seq to reconstruct gene expression in human organs and tumors.

DOI: 10.1038/s41587-020-00775-6

Source: https://www.nature.com/articles/s41587-020-00775-6

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