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bioRxiv · 10.64898/2026.01.04.697535

A cell-type-resolved human brain atlas of microRNAs and tRNA fragments

Dubnov, S.·Laski, L.·Zchut, I.·Avidan, O.·Bennett, E. R.·Greenberg, D. S.·Tujerman, A.·Nitzan, M.·Paldor, I.·Soreq, H.
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Abstract

MicroRNAs play key roles in regulating brain processes ranging from neurogenesis to neurological disease and contribute to many cell-type-specific pathways. However, technical limitations of single-cell small RNA sequencing have confined most studies to bulk analyses of whole-tissue specimens, limiting our capacity to resolve the cell-type specificity of brain microRNAs and to study their roles in depth. To generate a comprehensive, cell-type-resolved atlas of microRNAs in the human brain, we isolated neurons, astrocytes, microglia and oligodendrocytes from fresh neurosurgery-derived brain samples and profiled their small RNA repertoires by RNA sequencing. The results revealed pronounced cell-type-associated differences in microRNA profiles, identified novel cell-type-specific microRNA markers and shed new light on the contribution of their originating genomic loci to cell-type specificity. We further characterized the cell-type dependence of microRNA strand preference and isomiR processing, and identified cell-type-dependent microRNA programs associated with brain ageing. Combined with an accompanying statistical tool for cell-type signal enrichment, our atlas provides a publicly available resource for cell-type-resolved microRNA analysis in the human brain.

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Dubnov, S., Laski, L., Zchut, I., Avidan, O., Bennett, E. R., Greenberg, D. S., Tujerman, A., Nitzan, M., Paldor, I., Soreq, H.. 2026-01-04. A cell-type-resolved human brain atlas of microRNAs and tRNA fragments. https://doi.org/10.64898/2026.01.04.697535

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