利用針對血漿無細胞核小體的ChIP-seq鑑定細胞來源的基因表達基序
作者：
小柯機器人發布時間：2021/1/12 16:42:07
以色列耶路撒冷希伯來大學Nir Friedman研究團隊在研究中取得進展。他們利用針對血漿無細胞核小體的ChIP-seq鑑定了細胞來源的基因表達基序。相關論文於2021年1月11日發表於《自然-生物技術》雜誌。
在本研究中，研究人員利用染色質免疫沉澱檢測了無細胞核小體中活性染色質的修飾，並對268個人類樣品進行了測序（cfChIP-seq）。在健康供體中，研究人員發現骨髓巨核細胞而非成熟紅細胞是無細胞DNA（cfDNA）庫的主要來源。在患有一系列肝臟疾病的患者中，研究人員證明了其可以識別肝細胞轉錄過程中與病理相關的變化。在轉移性大腸癌患者中，研究人員檢測到了與臨床相關和患者特定的信息，包括轉錄活性人表皮生長因子受體2（HER2）的擴增。
總而言之，cfChIP-seq使用較低的測序深度，可提供系統的全基因組信息，並且可以提供診斷信息，有助於使用血樣進行生理和病理過程的追溯。
研究人員表示，人血漿中的cfDNA可提供有關器官或腫瘤病理起始過程的分子信息。這些DNA來自於死細胞中的染色質片段，並保留了一些來源細胞的組蛋白修飾。
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