【Seminar】"Unfolding the brain: reconstructing corticogenesis from cell maps" by Dr. Tatsuya C. Murakami

Abstract:

Single-cell-resolution mapping of the human brain is central to understanding the link between cellular-level phenotypes and disease. Tissue clearing and mesoscale imaging have facilitated organ-wide quantification of cell populations and are expected to drive the identification of pathological deficits in neurological disorders. However, mesoscopic comparison of human brain tissue remains challenging because of large heterogeneity in cortical folding patterns and uneven cell distribution.

Here, we present a retrodictive analysis of the cortex that reconstructs the proliferation history of neural stem cells from a static snapshot of tissue. Using the trajectories of radial glial fibers, we formulated a developmentally grounded coordinate transformation that serves as the basis of this retrodiction. With this transformation, we found that much of the apparent cell-population heterogeneity is accounted for by folding-induced displacement.

Within a Bayesian framework, we estimated, with quantified uncertainty, the proliferation rate of a representative stem cell summarizing each region's population. The retrodictive analysis enables researchers to distill inter-individual differences into a comparison of stem cell properties and their distributions on the protomap.

We anticipate our workflow, combined with multiplexed whole-mount in situ hybridization, to be a foundational framework for 3D neuropathological analysis, providing a common coordinate for the cortex-wide analysis of cells across individuals in development, aging, and disease.