小柯机器人

美国拉根MGH研究所Alex K. Shalek及Bruce D. Walker合作提出急性HIV-1感染期间多细胞免疫动力学的综合单细胞分析结果。相关论文发表在2020年3月23日出版的《自然-医学》杂志上。

他们介绍一种实验和计算方法，该方法使用单细胞RNA测序（scRNA-seq）表征动态细胞及其分子驱动进程，并将其应用于HIV感染。在急性感染之前和纵向期间，通过对来自四个未经治疗的个体的外周血单核细胞进行scRNA-seq测序，他们在每个人体内被发现了随时间和细胞亚群而变化的基因应答模块。除了以前未曾认识到的个体和细胞类型特异性干扰素刺激的基因上调以外，他们还描述了在时间上对齐的基因表达反应，这些分析在大量分析中被掩盖，包括那些参与促炎性T细胞分化，延长时间单核细胞主要组织相容性复合体II上调和持续性自然杀伤（ NK）细胞溶细胞杀伤。他们进一步确定了感染最初几周产生的反应特征，例如增殖的自然杀伤细胞，这可能与未来的病毒控制有关。总的来说，他们的方法为表征多个动态细胞反应及其协调提供了一个统一的框架。

据悉，细胞免疫对于控制细胞内病原体至关重要，但是人们对不断发展的人类免疫反应中的个体细胞动力学和细胞间协同性仍然知之甚少。scRNA-seq代表了一种强大的工具，可用于剖析健康和疾病中的复杂多细胞行为，并指定可测试的治疗靶标。它在纵向样本中的应用可以提供揭露与疾病进展相关的细胞因子的机会，而不会混淆个体间的变异性。

附：英文原文

Title: Integrated single-cell analysis of multicellular immune dynamics during hyperacute HIV-1 infection

Author: Samuel W. Kazer, Toby P. Aicher, Daniel M. Muema, Shaina L. Carroll, Jose Ordovas-Montanes, Vincent N. Miao, Ang A. Tu, Carly G. K. Ziegler, Sarah K. Nyquist, Emily B. Wong, Nasreen Ismail, Mary Dong, Amber Moodley, Bonnie Berger, J. Christopher Love, Krista L. Dong, Alasdair Leslie, Zaza M. Ndhlovu, Thumbi Ndungu, Bruce D. Walker, Alex K. Shalek

Issue&Volume: 2020-03-23

Abstract: Cellular immunity is critical for controlling intracellular pathogens, but individual cellular dynamics and cell–cell cooperativity in evolving human immune responses remain poorly understood. Single-cell RNA-sequencing (scRNA-seq) represents a powerful tool for dissecting complex multicellular behaviors in health and disease1,2 and nominating testable therapeutic targets3. Its application to longitudinal samples could afford an opportunity to uncover cellular factors associated with the evolution of disease progression without potentially confounding inter-individual variability4. Here, we present an experimental and computational methodology that uses scRNA-seq to characterize dynamic cellular programs and their molecular drivers, and apply it to HIV infection. By performing scRNA-seq on peripheral blood mononuclear cells from four untreated individuals before and longitudinally during acute infection5, we were powered within each to discover gene response modules that vary by time and cell subset. Beyond previously unappreciated individual- and cell-type-specific interferon-stimulated gene upregulation, we describe temporally aligned gene expression responses obscured in bulk analyses, including those involved in proinflammatory T cell differentiation, prolonged monocyte major histocompatibility complex II upregulation and persistent natural killer (NK) cell cytolytic killing. We further identify response features arising in the first weeks of infection, for example proliferating natural killer cells, which potentially may associate with future viral control. Overall, our approach provides a unified framework for characterizing multiple dynamic cellular responses and their coordination.

DOI: 10.1038/s41591-020-0799-2

Source: https://www.nature.com/articles/s41591-020-0799-2

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex