Progenitor cells play vital roles in maintaining optimal organismal functions under normal physiological, aged, or diseased conditions. However, progenitor cells are understudied, particularly in the brain, due in part to inadequate tools and resolution for deciphering cell-type-specific proliferation and differentiation dynamics in vivo. Adult mammals’ brains are constantly producing new neurons and glial cells. These cells’ production is significant and links to higher cognitive functions such as memory, learning, and stress. The development of neuronal cells decreases with age and other nervous system pathologies. However, the precise magnitude of these declines is unknown. These ambiguities arise due to research limitations in effectively quantifying the identity of progenitor cells.
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Brain Imaging
Although several studies have shed light on the gene expression of progenitor cells in the adult brain, much remains unknown about the dynamics of progenitor cells in vivo. In this new study, a team of researchers developed a novel method for tracking the proliferation and differentiation dynamics of newborn cells in the mammalian brain.
TrackerSci is a new tool for labeling newborn cells in vivo
TrackerSci is a novel technique that combines in vivo labeling of newborn cells with single-cell combinatorial indexing to profile the chromatin landscape and transcriptome of rare progenitor cells and track cellular differentiation trajectories in vivo. TrackerSci was used to examine newborn cells’ epigenetic and gene expression dynamics across entire mouse brains at three different ages and in an Alzheimer’s disease mouse model. Using the dataset, the researchers identified diverse progenitor cell types previously unknown in single-cell analysis and recovered their distinct epigenetic signatures.
The researchers also quantified progenitor cells’ cell-type-specific proliferation and differentiation potentials, as well as molecular programs underlying their aging-related changes (e.g., reduced neurogenesis/oligodendrogenesis). The scientists extended the study to investigate progenitor cells in the aged human brain by profiling 800,000 single-cell transcriptomes from six old human brains across five anatomical regions. They also looked into the transcriptome signatures that are shared or divergent between human and mouse oligodendrogenesis, with region-specific oligodendrogenesis down-regulation in the human cerebellum. The findings provide an in-depth look at rare progenitor cells in mammalian brains.
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Clinical significance
The novel findings from the study provide an in-depth view of rare progenitor cells in mammalian brains. The developed TrackerSci can have enormous possibilities in medical practice. The researchers anticipate a broad application of the tool to characterize cell-type-specific temporal dynamics in diverse systems. The computational and experimental methods described in the study can also help track cellular regenerative capacity and differentiation potential across mammalian organs and other biological systems.
Conclusion
The current study solves the limitations of inadequate tools to study progenitor cells. The application of TrackerSci can allow for better organ mapping and to identify progenitor cell types previously unknown in the brains of human and mouse models. The study also helps scientists understand similarities and differences in transcriptome signatures in humans and mice.
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References
A comprehensive view of cell-type-specific temporal dynamics in human and mouse brains
