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

Journal: Nature communications
PMID:

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.

Authors

  • Theo Perochon
    Group of Data Modeling and Computational Biology, IBENS, École Normale Supérieure, Paris, France.
  • Željka Krsnik
    Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia.
  • Marco Massimo
    Centre for Developmental Neurobiology, MRC Centre for Neurodevelopmental Disorders, King's College London, London, UK.
  • Yana Ruchiy
    Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden.
  • Alejandro Lastra Romero
    Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden.
  • Elyas Mohammadi
    Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Solna, Sweden.
  • Xiaofei Li
    Department of Infectious Diseases, YiWu Central Hospita, Zhejiang, 322000, China. Electronic address: xiaofeil2021@163.com.
  • Katherine R Long
    Centre for Developmental Neurobiology, MRC Centre for Neurodevelopmental Disorders, King's College London, London, UK.
  • Laura Parkkinen
    Department of Neuropathology and The Queen's College, University of Oxford, Oxford, United Kingdom.
  • Klas Blomgren
    Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden.
  • Thibault Lagache
    Institut Pasteur, BioImage Analysis Unit, CNRS UMR 3691, Paris, France.
  • David A Menassa
    Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden. david.menassa@queens.ox.ac.uk.
  • David Holcman
    Group of Data Modeling and Computational Biology, IBENS, École Normale Supérieure, Paris, France. david.holcman@ens.psl.eu.