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  3. Picower Plastic Lunch: Brent Fitzwalter "Single-cell genomic studies reveal the molecular properties and disease susceptibility factors of the human cerebellum"
Picower Plastic Lunch: Josefina Correa Menendez & Brent Fitzwalter
The Picower Institute for Learning and Memory

Picower Plastic Lunch: Brent Fitzwalter "Single-cell genomic studies reveal the molecular properties and disease susceptibility factors of the human cerebellum"

Add to CalendarAmerica/New_YorkPicower Plastic Lunch: Brent Fitzwalter "Single-cell genomic studies reveal the molecular properties and disease susceptibility factors of the human cerebellum"12/07/2023 12:00 pm12/07/2023 1:00 pmBuilding 46,Picower Seminar Room (46-3310, 3rd floor of MIT Building 46)
December 7, 2023
12:00 pm - 1:00 pm
Location
Building 46,Picower Seminar Room (46-3310, 3rd floor of MIT Building 46)
Contact
bgreeno@mit.edu
    Description

    Picower Plastic Lunch

    Speaker: Brent Fitzwalter, Postdoctoral Fellow, Heiman Lab

    Thursday, November 30 | 12-1pm | 46-3310

    Title: Single-cell genomic studies reveal the molecular properties and disease susceptibility factors of the human cerebellum

    Abstract: The cerebellum is a brain region important for motor control, motor learning, and cognition, but there is to date no complete atlas of the diverse cell types that constitute the adult human cerebellar cortex. Given the susceptibility of the cerebellum across multiple disorders including autism, CAG repeat neurodegenerative diseases, and medulloblastoma, there is a pressing clinical need to better understand the molecular properties of the cells that comprise the human cerebellar cortex. One difficulty of applying single-cell techniques to the study of the cerebellum is that specific cell types, such as the Purkinje cell (PC)—a critical GABAergic projection neuron of the cerebellum—are of low abundance in cerebellar tissue. To overcome this hurdle, we developed a novel method to enrich for PCs and other rare cerebellar cell types from bulk human cerebellar tissue, thus enabling us to study all human cerebellar cell types with single-cell techniques. We levered this approach to generate a complete transcriptomic atlas of the human cerebellar cortex, including the rare PC population. We capture 286,647 human cells across the cerebellar vermis and hemisphere, including >11,000 PCs consisting of three major molecular subtypes. We identify cell type-specific markers of human cerebellar cells, and reveal species-specific gene expression differences. We find that PCs possess a transcriptomic signature that shares features with striatal GABAergic projection neurons—a cell type that, like PCs, displays vulnerability across several CAG repeat disorders including Huntington’s disease. In addition to this common transcriptomic signature, we reveal that, like striatal GABAergic projection neurons, PCs also display somatic CAG repeat instability of the mutant Huntingtin gene. Taken together, our study provides not only a comprehensive molecular atlas of the human cerebellar cortex, but also reveals new insights into the basis of the intrinsic susceptibility of GABAergic neurons in CAG repeat disorders.

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