小柯机器人

科学家绘制出人类小胶质细胞的转录异质性和调控变异图谱
2021-06-06 15:36

英国剑桥大学Daniel J. Gaffney、Robin J. M. Franklin等研究人员合作绘制出人类小胶质细胞的转录异质性和调控变异图谱。该研究于2021年6月3日在线发表于国际一流学术期刊《自然—遗传学》。

研究人员分析了从141名接受神经外科手术的患者中分离出的原代人类小胶质细胞基因表达变异。通过单细胞和大量RNA测序,研究人员使用表达数量性状基因座(eQTL)映射确定年龄、性别和临床病理学如何影响小胶质细胞基因表达以及哪些遗传变异具有小胶质细胞特异性功能。

研究人员使用基于人类诱导多能干细胞的巨噬细胞模型对其中一项发现进行了跟进,并精细定位了BIN1基因座上阿尔茨海默病的候选因果变异。因此,该研究提供了一个对人类中枢神经系统发育和疾病中重要细胞的群体规模转录图谱。

据悉,小胶质细胞是中枢神经系统的组织驻留巨噬细胞,在免疫防御、发育和体内平衡中起着关键作用。然而,从大量人类中分离出小胶质细胞具有挑战性。

附:英文原文

Title: A map of transcriptional heterogeneity and regulatory variation in human microglia

Author: Adam M. H. Young, Natsuhiko Kumasaka, Fiona Calvert, Timothy R. Hammond, Andrew Knights, Nikolaos Panousis, Jun Sung Park, Jeremy Schwartzentruber, Jimmy Liu, Kousik Kundu, Michael Segel, Natalia A. Murphy, Christopher E. McMurran, Harry Bulstrode, Jason Correia, Karol P. Budohoski, Alexis Joannides, Mathew R. Guilfoyle, Rikin Trivedi, Ramez Kirollos, Robert Morris, Matthew R. Garnett, Ivan Timofeev, Ibrahim Jalloh, Katherine Holland, Richard Mannion, Richard Mair, Colin Watts, Stephen J. Price, Peter J. Kirkpatrick, Thomas Santarius, Edward Mountjoy, Maya Ghoussaini, Nicole Soranzo, Omer A. Bayraktar, Beth Stevens, Peter J. Hutchinson, Robin J. M. Franklin, Daniel J. Gaffney

Issue&Volume: 2021-06-03

Abstract: Microglia, the tissue-resident macrophages of the central nervous system (CNS), play critical roles in immune defense, development and homeostasis. However, isolating microglia from humans in large numbers is challenging. Here, we profiled gene expression variation in primary human microglia isolated from 141 patients undergoing neurosurgery. Using single-cell and bulk RNA sequencing, we identify how age, sex and clinical pathology influence microglia gene expression and which genetic variants have microglia-specific functions using expression quantitative trait loci (eQTL) mapping. We follow up one of our findings using a human induced pluripotent stem cell-based macrophage model to fine-map a candidate causal variant for Alzheimer’s disease at the BIN1 locus. Our study provides a population-scale transcriptional map of a critically important cell for human CNS development and disease.

DOI: 10.1038/s41588-021-00875-2

Source: https://www.nature.com/articles/s41588-021-00875-2

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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