Unraveling microglial spatial organization in the developing human brain with DeepCellMap, a deep learning approach coupled with spatial statistics

Theo Perochon, Zeljka Krsnik, Marco Massimo, Yana Ruchiy, Alejandro Lastra Romero, Elyas Mohammadi, Xiaofei Li, Katherine R. Long, Laura Parkkinen, Klas Blomgren, Thibault Lagache (), David A. Menassa () and David Holcman ()
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Theo Perochon: École Normale Supérieure
Zeljka Krsnik: University of Zagreb
Marco Massimo: King’s College London
Yana Ruchiy: Karolinska Institutet
Alejandro Lastra Romero: Karolinska Institutet
Elyas Mohammadi: Karolinska Institutet
Xiaofei Li: Karolinska Institutet
Katherine R. Long: King’s College London
Laura Parkkinen: University of Oxford
Klas Blomgren: Karolinska Institutet
Thibault Lagache: Université Paris Cité
David A. Menassa: Karolinska Institutet
David Holcman: École Normale Supérieure

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Mapping cellular organization in the developing brain presents significant challenges due to the multidimensional nature of the data, characterized by complex spatial patterns that are difficult to interpret without high-throughput tools. Here, we present DeepCellMap, a deep-learning-assisted tool that integrates multi-scale image processing with advanced spatial and clustering statistics. This pipeline is designed to map microglial organization during normal and pathological brain development and has the potential to be adapted to any cell type. Using DeepCellMap, we capture the morphological diversity of microglia, identify strong coupling between proliferative and phagocytic phenotypes, and show that distinct spatial clusters rarely overlap as human brain development progresses. Additionally, we uncover an association between microglia and blood vessels in fetal brains exposed to maternal SARS-CoV-2. These findings offer insights into whether various microglial phenotypes form networks in the developing brain to occupy space, and in conditions involving haemorrhages, whether microglia respond to, or influence changes in blood vessel integrity. DeepCellMap is available as an open-source software and is a powerful tool for extracting spatial statistics and analyzing cellular organization in large tissue sections, accommodating various imaging modalities. This platform opens new avenues for studying brain development and related pathologies.

Date: 2025
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DOI: 10.1038/s41467-025-56560-z

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