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École Polytechnique Fédérale de Lausanne, Switzerland
Astrocytes, one of the major cell types in the CNS, perform a variety of roles crucial for brain physiology, neuronal function and synaptic transmission. Despite multiple functions, morphological variability, and distinct anatomical locations, decades-long assumptions stated that astrocytes are generally homogeneous cells. Although, this notion was often questioned in recent years.
To investigate the true extent of astrocyte molecular diversity across forebrain regions, we used single-cell RNA sequencing. Our analysis identified five transcriptionally distinct astrocyte subtypes in adult mouse cortex and hippocampus. In situ validation of our data revealed distinct spatial positioning of defined subtypes, reflecting the distribution of morphologically and physiologically distinct astrocyte populations. Our findings revealed the complexity of astrocyte heterogeneity, and hinted towards developmental and tissue micro-environment factors as possible bases of astrocyte heterogeneity.
Batiuk, M.Y., de Vin, F., Duqué, S.I., Li, C., Saito, T., Saido, T., Fiers, M., Belgard, T.G., Holt, M.G., 2017. An immunoaffinity-based method for isolating ultrapure adult astrocytes based on ATP1B2 targeting by the ACSA-2 antibody. J. Biol. Chem. 292, 8874–8891.
Batiuk, M.Y., Martirosyan, A., Wahis, J., de Vin, F., Marneffe, C., Kusserow, C., Koeppen, J., Viana, J.F., Oliveira, J.F., Voet, T., Ponting, C.P., Belgard, T.G., Holt, M.G., 2020. Identification of region-specific astrocyte subtypes at single cell resolution. Nat. Commun. 11, 1220.
Bayraktar, O.A., Bartels, T., Holmqvist, S., Kleshchevnikov, V., Martirosyan, A., Polioudakis, D., Ben Haim, L., Young, A.M.H., Batiuk, M.Y., Prakash, K., Brown, A., Roberts, K., Paredes, M.F., Kawaguchi, R., Stockley, J.H., Sabeur, K., Chang, S.M., Huang, E., Hutchinson, P., Ullian, E.M., Hemberg, M., Coppola, G., Holt, M.G., Geschwind, D.H., Rowitch, D.H., 2020. Astrocyte layers in the mammalian cerebral cortex revealed by a single-cell in situ transcriptomic map. Nat. Neurosci. 23, 500–509.
Pfisterer, U., Petukhov, V., Demharter, S., Meichsner, J., Thompson, J.J., Batiuk, M.Y., Asenjo-Martinez, A., Vasistha, N.A., Thakur, A., Mikkelsen, J., Adorjan, I., Pinborg, L.H., Pers, T.H., von Engelhardt, J., Kharchenko, P. V, Khodosevich, K., 2020. Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis. Nat. Commun. 11, 5038.