小胶质细胞的转录状态及其功能意义：环境驱动多样性。

Microglia transcriptional states and their functional significance: Context drives diversity.

作者信息

Depp Constanze, Doman Jordan L, Hingerl Maximilian, Xia Judy, Stevens Beth

机构信息

Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA; The Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA; The Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Society of Fellows, Harvard University, Cambridge, MA, USA.

出版信息

Immunity. 2025 May 13;58(5):1052-1067. doi: 10.1016/j.immuni.2025.04.009. Epub 2025 May 6.

DOI:10.1016/j.immuni.2025.04.009

PMID:40328255

Abstract

In the brain, microglia are continuously exposed to a dynamic microenvironment throughout life, requiring them to adapt accordingly to specific developmental or disease-related demands. The advent of single-cell sequencing technologies has revealed the diversity of microglial transcriptional states. In this review, we explore the various contexts that drive transcriptional diversity in microglia and assess the extent to which non-homeostatic conditions induce context-specific signatures. We discuss our current understanding and knowledge gaps regarding the relationship between transcriptional states and microglial function, review the influence of complex microenvironments and prior experiences on microglial state induction, and highlight strategies to bridge the gap between mouse and human studies to advance microglia-targeting therapeutics.

摘要

在大脑中，小胶质细胞在整个生命过程中持续暴露于动态的微环境中，这要求它们相应地适应特定的发育或疾病相关需求。单细胞测序技术的出现揭示了小胶质细胞转录状态的多样性。在本综述中，我们探讨了驱动小胶质细胞转录多样性的各种情况，并评估了非稳态条件诱导特定背景特征的程度。我们讨论了目前对转录状态与小胶质细胞功能之间关系的理解以及知识空白，回顾了复杂微环境和既往经历对小胶质细胞状态诱导的影响，并强调了弥合小鼠和人类研究之间差距以推进小胶质细胞靶向治疗的策略。