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Aims: We sought to identify and optimise a universally available histological marker for pericytes in the human brain. Such a marker could be a useful tool for researchers. Further, identifying a gene expressed relatively specifically in human pericytes could provide new insights into the biological functions of this fascinating cell type. Methods: We analysed single‐cell RNA expression profiles derived from different human and mouse brain regions using a high‐throughput and low‐cost single‐cell transcriptome sequencing method called EasySci. Through this analysis, we were able to identify specific gene markers for pericytes, some of which had not been previously characterised. We then used commercially (and therefore universally) available antibodies to immunolabel the pericyte‐specific gene products in formalin‐fixed paraffin‐embedded (FFPE) human brains and also performed immunoblots to determine whether appropriately sized proteins were recognised. Results: In the EasySci data sets, highly pericyte‐enriched expression was notable for SLC6A12 and SLC19A1. Antibodies against these proteins recognised bands of approximately the correct size in immunoblots of human brain extracts. Following optimisation of the immunohistochemical technique, staining for both antibodies was strongly positive in small blood vessels and was far more effective than a PDGFRB antibody at staining pericyte‐like cells in FFPE human brain sections. In an exploratory sample of other human organs (kidney, lung, liver, muscle), immunohistochemistry did not show the same pericyte‐like pattern of staining. Conclusions: The SLC6A12 antibody was well suited for labelling pericytes in human FFPE brain sections, based on the combined results of single‐cell RNA‐seq analyses, immunoblots and immunohistochemical studies. [ABSTRACT FROM AUTHOR]

This document is a response letter from Peter T. Nelson, Andras Sziraki, and Junyue Cao in the journal Neuropathology & Applied Neurobiology. The authors acknowledge that their literature search failed to cite an important paper by Drs. Gurler and Yemisci on retinal pericytes. They also highlight that pericyte markers may differ across different organs and species, and that specific markers for pericytes are crucial in research. The authors express gratitude for the letter and express interest in learning more about pericytes in various contexts. [Extracted from the article]

Progenitor cells are critical in preserving organismal homeostasis, yet their diversity and dynamics in the aged brain remain underexplored. We introduced TrackerSci , a single-cell genomic method that combines newborn cell labeling and combinatorial indexing to characterize the transcriptome and chromatin landscape of proliferating progenitor cells in vivo. Using TrackerSci , we investigated the dynamics of newborn cells in mouse brains across various ages and in a mouse model of Alzheimer's disease. Our dataset revealed diverse progenitor cell types in the brain and their epigenetic signatures. We further quantified aging-associated shifts in cell-type-specific proliferation and differentiation and deciphered the associated molecular programs. Extending our study to the progenitor cells in the aged human brain, we identified conserved genetic signatures across species and pinpointed region-specific cellular dynamics, such as the reduced oligodendrogenesis in the cerebellum. We anticipate that TrackerSci will be broadly applicable to unveil cell-type-specific temporal dynamics in diverse systems. [Display omitted] • TrackerSci for characterizing the diversity and dynamics of progenitor cells in vivo • The epigenetic and genetic signatures of brain progenitor cell types • Aging-associated cell-type-specific alterations in proliferation and differentiation • Region-specific changes of oligodendrogenesis in the aged human brain A comprehensive view of single-cell transcriptome and chromatin accessibility dynamics of brain newborn cells provides insights into aging-associated shifts in cell-type-specific proliferation and differentiation and associated molecular programs. [ABSTRACT FROM AUTHOR]