Through single-cell RNA sequencing of 225,382 individual transcriptomes from 74 donors, Tuddenham et al. investigated microglial heterogeneity across neurodegenerative diseases.

The researchers out of the Jager lab identified 12 distinct microglial subpopulations and proposed trajectories of cell-state transitions, revealing a central metabolic shift between oxidative and heterocyclic metabolism.

The study utilised diaPASEF-based proteomics to complement their RNA based findings, analysing compound-treated HMC3 microglia cells with compounds including camptothecin, narciclasine, and Torin-2.

The IonOpticks Aurora Ultimate CSI 25×75 C18 UHPLC column enabled precise peptide separation at 400 nl/min flow rate over 120-minute gradients, contributing to the comprehensive proteomic profiling that validated the transcriptomic findings.

This study provides a valuable resource for understanding microglial diversity in human neurodegeneration and establishes new tools for identifying and manipulating microglial subtypes in situ.

Publication
Nature Neuroscience

Authors

John F. Tuddenham, Mariko Taga, Verena Haage, Victoria S. Marshe, Tina Roostaei, Charles White, Annie J. Lee, Masashi Fujita, Anthony Khairallah, Ya Zhang, Gilad Green, Bradley Hyman, Matthew Frosch, Sarah Hopp, Thomas G. Beach, Geidy E. Serrano, John Corboy, Naomi Habib, Hans-Ulrich Klein, Rajesh Kumar Soni, Andrew F. Teich, Richard A. Hickman, Roy N. Alcalay, Neil Shneider, Julie Schneider, Peter A. Sims, David A. Bennett, Marta Olah, Vilas Menon, Philip L. De Jager

Title

A cross-disease resource of living human microglia identifies disease-enriched subsets and tool compounds recapitulating microglial states