Tracking cell-type-specific temporal dynamics in human and mouse brains

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.

Automated summary

Progenitor cells in the aged brain play a critical role in maintaining organismal homeostasis, but their diversity and dynamics have been overlooked. A new single-cell genomic method called TrackerSci was introduced to characterize the transcriptome and chromatin landscape of proliferating progenitor cells in vivo. The study revealed diverse progenitor cell types in the brain and identified aging-associated shifts in cell-type-specific proliferation and differentiation. Conserved genetic signatures across species were also discovered in the progenitor cells of the aged human brain, along with region-specific cellular dynamics.