Single Cell Transcriptional Signatures of Microglia and Monocytes after ICH

To better characterise myeloid cell changes over time, we employed single-cell RNA sequencing to generate a unique paired dataset of live haematoma and peripheral blood samples from 10 ICH patients. This work presents a temporal atlas of ICH myeloid populations and identifies population-specific in-situ transcriptional drivers.

In addition to distinct populations of activated microglia and TNF-low microglia, we found a unique and highly activated population of CD14+ monocytes in the haematoma. Perturbation analysis comparing haematoma-associated monocytes to shared populations in blood and haematomas identified TNF signalling as the primary driver of their activation. Employing a custom temporal trajectory analysis based on the embeddings of a single-cell foundation model, we found that this TNF response in monocytes was transient, peaking early after haemorrhage and decreasing over the ensuing 48 hours.