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

Area of Science:

• Neuroscience
• Genomics
• Cell Biology

Background:

• Progenitor cells are vital for maintaining brain homeostasis.
• Their diversity and dynamics in the aged brain are not well understood.
• Aging and neurodegenerative diseases impact progenitor cell function.

Purpose of the Study:

• To introduce TrackerSci, a single-cell genomic method for analyzing progenitor cells.
• To investigate the dynamics of newborn cells in aging and Alzheimer's disease mouse models.
• To characterize progenitor cell diversity, epigenetic signatures, and aging-associated changes in the brain.

Main Methods:

• TrackerSci combines newborn cell labeling and combinatorial indexing.
• Single-cell RNA sequencing and ATAC sequencing were employed.
• Analysis was performed on mouse brains across different ages and in an Alzheimer's disease model.
• Progenitor cells from aged human brains were also studied.

Main Results:

• Diverse progenitor cell types and their epigenetic landscapes were identified.
• Aging-associated shifts in cell-type-specific proliferation and differentiation were quantified.
• Molecular programs underlying these age-related changes were deciphered.
• Conserved genetic signatures and region-specific dynamics, like reduced oligodendrogenesis in the cerebellum, were found in aged human brains.

Conclusions:

• TrackerSci effectively characterizes the transcriptome and chromatin landscape of progenitor cells in vivo.
• The study provides insights into the aging brain's cellular dynamics and molecular mechanisms.
• Findings highlight conserved aging signatures across species and identify region-specific cellular changes.
• TrackerSci is a powerful tool for studying cell-type-specific temporal dynamics in various biological systems.