美国白头生物医学研究所Rudolf Jaenisch研究小组发现，快速吞噬体分离技术实现对人类小胶质细胞吞噬体的无偏多组学分析。该研究于2024年8月15日在线发表于国际一流学术期刊《免疫》。

研究人员开发了一种方法，能够从不同体外条件下的人类多能干细胞来源的小胶质细胞以及人脑活检样本中快速分离出纯净且完整的吞噬体，进行无偏的多组学分析。吞噬体的分析显示，小胶质细胞吞噬体能够感知其环境中的微小变化，且具有高度动态性。

研究人员检测到了参与突触稳态调节或与脑部病理相关的蛋白质，并发现吞噬体是喹啉酸储存和代谢的部位，通过这一过程在细胞质中生成新生烟酰胺腺嘌呤二核苷酸（NAD⁺）。这些研究结果强调了吞噬体在健康和疾病状态下小胶质细胞功能中的核心作用。

研究人员表示，小胶质细胞是中枢神经系统（CNS）中的常驻巨噬细胞，其吞噬活动在大脑发育、稳态维持以及多种脑部病理中起着核心作用。然而，关于人类小胶质细胞吞噬体在稳态和病理条件下的组成、动态及功能的了解仍然有限。

附：英文原文

Title: Rapid phagosome isolation enables unbiased multiomic analysis of human microglial phagosomes

Author: Emile Wogram, Felix Sümpelmann, Wentao Dong, Eshaan Rawat, Inés Fernández Maestre, Dongdong Fu, Brandyn Braswell, Andrew Khalil, Joerg M. Buescher, Gerhard Mittler, Georg H.H. Borner, Andreas Vlachos, Stefan Tholen, Oliver Schilling, George W. Bell, Angelika S. Rambold, Asifa Akhtar, Oliver Schnell, Jürgen Beck, Monther Abu-Remaileh, Marco Prinz, Rudolf Jaenisch

Issue&Volume: 2024-08-15

Abstract: Microglia are the resident macrophages of the central nervous system (CNS). Theirphagocytic activity is central during brain development and homeostasis—and in a plethoraof brain pathologies. However, little is known about the composition, dynamics, andfunction of human microglial phagosomes under homeostatic and pathological conditions.Here, we developed a method for rapid isolation of pure and intact phagosomes fromhuman pluripotent stem cell-derived microglia under various in vitro conditions, and from human brain biopsies, for unbiased multiomic analysis. Phagosomeprofiling revealed that microglial phagosomes were equipped to sense minute changesin their environment and were highly dynamic. We detected proteins involved in synapsehomeostasis, or implicated in brain pathologies, and identified the phagosome as thesite where quinolinic acid was stored and metabolized for de novo nicotinamide adenine dinucleotide (NAD+) generation in the cytoplasm. Our findings highlight the central role of phagosomesin microglial functioning in the healthy and diseased brain.

DOI: 10.1016/j.immuni.2024.07.019

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00368-6