科學家繪製出人類肺臟的單細胞RNA測序圖譜
作者:
小柯機器人發布時間:2020/11/22 23:41:19
美國史丹福大學Mark A. Krasnow、Stephen R. Quake等研究人員合作繪製出人類肺臟的單細胞RNA測序圖譜。2020年11月18日,《自然》雜誌在線發表了這項成果。
研究人員使用基於液滴和平板的單細胞RNA測序技術,對所有肺組織隔室和循環血液中的大約75,000個人類細胞進行了測序,並結合了多種細胞注釋方法,從而創建了人類肺的廣泛細胞圖譜。研究人員定義了人類肺臟中58個細胞群體的基因表達譜和解剖位置,包括45種先前已知的細胞類型中的41種和14種先前未知的細胞類型。
這個全面的分子圖譜鑑定了肺細胞的生化功能以及轉錄因子和用於製造和監測它們的標記物;定義循環激素的細胞靶標,並預測局部信號相互作用和免疫細胞歸巢;並確定直接受到肺部疾病基因和呼吸道病毒影響的細胞類型。通過比較人類和小鼠的數據,研究人員鑑定了17種在肺進化過程中獲得或喪失的分子細胞類型,而其他分子的表達譜卻發生了大幅變化,這揭示了器官類型在細胞表達過程中廣泛的可塑性和特定於細胞類型的基因表達。
該圖譜為研究如何在發育和組織工程中實現肺細胞身份、功能和相互作用以及在疾病和進化中發生改變提供了分子基礎。
據了解,儘管單細胞RNA測序研究已提供了細胞表達譜的報導,但很難系統地鑑定和定位單個器官中的所有分子細胞類型,從而創建完整的分子細胞圖譜。
附:英文原文
Title: A molecular cell atlas of the human lung from single-cell RNA sequencing
Author: Kyle J. Travaglini, Ahmad N. Nabhan, Lolita Penland, Rahul Sinha, Astrid Gillich, Rene V. Sit, Stephen Chang, Stephanie D. Conley, Yasuo Mori, Jun Seita, Gerald J. Berry, Joseph B. Shrager, Ross J. Metzger, Christin S. Kuo, Norma Neff, Irving L. Weissman, Stephen R. Quake, Mark A. Krasnow
Issue&Volume: 2020-11-18
Abstract: Although single-cell RNA sequencing studies have begun to provide compendia of cell expression profiles1,2,3,4,5,6,7,8,9, it has been difficult to systematically identify and localize all molecular cell types in individual organs to create a full molecular cell atlas. Here, using droplet- and plate-based single-cell RNA sequencing of approximately 75,000 human cells across all lung tissue compartments and circulating blood, combined with a multi-pronged cell annotation approach, we create an extensive cell atlas of the human lung. We define the gene expression profiles and anatomical locations of 58 cell populations in the human lung, including 41 out of 45 previously known cell types and 14 previously unknown ones. This comprehensive molecular atlas identifies the biochemical functions of lung cells and the transcription factors and markers for making and monitoring them; defines the cell targets of circulating hormones and predicts local signalling interactions and immune cell homing; and identifies cell types that are directly affected by lung disease genes and respiratory viruses. By comparing human and mouse data, we identified 17 molecular cell types that have been gained or lost during lung evolution and others with substantially altered expression profiles, revealing extensive plasticity of cell types and cell-type-specific gene expression during organ evolution including expression switches between cell types. This atlas provides the molecular foundation for investigating how lung cell identities, functions and interactions are achieved in development and tissue engineering and altered in disease and evolution.
DOI: 10.1038/s41586-020-2922-4
Source: https://www.nature.com/articles/s41586-020-2922-4