Single-cell transcriptomics and In situ morphological analyses reveal microglia heterogeneity across the nigrostriatal pathway

Oihane Uriarte Huarte, Dimitrios Kyriakis, Tony Heurtaux, Yolanda Pires-Afonso, Kamil Grzyb, Rashi Halder, Manuel Buttini, Alexander Skupin, Michel Mittelbronn, Alessandro Michelucci*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

27 Citations (Scopus)


Microglia are the resident immune effector cells of the central nervous system (CNS) rapidly reacting to various pathological stimuli to maintain CNS homeostasis. However, microglial reactions in the CNS may also worsen neurological disorders. Hence, the phenotypic analysis of microglia in healthy tissue may identify specific poised subsets ultimately supporting or harming the neuronal network. This is all the more important for the understanding of CNS disorders exhibiting regional-specific and cellular pathological hallmarks, such as many neurodegenerative disorders, including Parkinson’s disease (PD). In this context, we aimed to address the heterogeneity of microglial cells in susceptible brain regions for PD, such as the nigrostriatal pathway. Here, we combined single-cell RNA-sequencing with immunofluorescence analyses of the murine nigrostriatal pathway, the most affected brain region in PD. We uncovered a microglia subset, mainly present in the midbrain, displaying an intrinsic transcriptional immune alerted signature sharing features of inflammation-induced microglia. Further, an in situ morphological screening of inferred cellular diversity showed a decreased microglia complexity in the midbrain when compared to striatum. Our study provides a resource for the identification of specific microglia phenotypes within the nigrostriatal pathway, which may be relevant in PD.

Original languageEnglish
Article number639613
Pages (from-to)639613
JournalFrontiers in Immunology
Publication statusPublished - 29 Mar 2021


  • Parkinson’s disease
  • cell morphology
  • cellular heterogeneity
  • immune alerted
  • microglia
  • nigrostriatal pathway
  • single-cell transcriptomics


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