研究揭示肺中髓系細胞多樣性的轉錄組和表觀遺傳機制

研究揭示肺中髓系細胞多樣性的轉錄組和表觀遺傳機制

作者：

小柯機器人

發布時間：2020/1/25 10:53:38

美國加州大學聖地牙哥分校Eniko Sajti等研究人員的一項最新工作揭示了肺中髓系細胞多樣性的轉錄組和表觀遺傳機制。2020年1月20日，《自然—免疫學》在線發表了這項成果。

利用來自兩個小鼠品系的肺泡巨噬細胞（AM）、間質巨噬細胞（IM）和肺單核細胞的轉錄組和開放染色質的系統評估，研究人員能夠推斷出共同的以及細胞特異性的轉錄調節因子。研究人員提供的證據表明，這些因素驅動調節網絡的選擇，從而指導AM和IM的不同表型並在體內對Toll樣受體4信號傳遞產生不同響應。這些研究揭示了AM中基本先天免疫應答途徑的顯著差異，並為進一步了解肺中的巨噬細胞多樣性建立了框架。

 

據介紹，肺中常有肺泡和間質巨噬細胞以及監測肺組織的單核細胞。每種細胞類型在穩態和炎症條件下均發揮不同的功能作用，但建立其分子身份和功能潛力的機制仍知之甚少。 

 

附：英文原文

Title: Transcriptomic and epigenetic mechanisms underlying myeloid diversity in the lung

Author: Eniko Sajti, Verena M. Link, Zhengyu Ouyang, Nathanael J. Spann, Emma Westin, Casey E. Romanoski, Gregory J. Fonseca, Lawrence S. Prince, Christopher K. Glass

Issue&Volume: 2020-01-20

Abstract: The lung is inhabited by resident alveolar and interstitial macrophages as well as monocytic cells that survey lung tissues. Each cell type plays distinct functional roles under homeostatic and inflammatory conditions, but mechanisms establishing their molecular identities and functional potential remain poorly understood. In the present study, systematic evaluation of transcriptomes and open chromatin of alveolar macrophages (AMs), interstitial macrophages (IMs) and lung monocytes from two mouse strains enabled inference of common and cell-specific transcriptional regulators. We provide evidence that these factors drive selection of regulatory landscapes that specify distinct phenotypes of AMs and IMs and entrain qualitatively different responses to toll-like receptor 4 signaling in vivo. These studies reveal a striking divergence in a fundamental innate immune response pathway in AMs and establish a framework for further understanding macrophage diversity in the lung.

DOI: 10.1038/s41590-019-0582-z

Source: https://www.nature.com/articles/s41590-019-0582-z