Tissue Mapping Center

 

University of Connecticut School of Medicine and Dentistry

High resolution 3D mapping of cellular heterogeneity within articular cartilage

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This group will utilize a protocol that is capable of performing multimodal histology that includes methods for advanced and repetitive in situ hybridization. This will be applied to the distal end of the femur with a primary focus on the articular cartilage.

The team acquires femoral tissues from de-identified human sources. Each sample is oriented to its source tissue, imaged by µCT to capture its mineral structure and processed into a histological stack to create a 3D representation of the tissue. Using the histological stack, the Mineralized Tissue Program performs both smFISH and MERFISH in situ hybridization approaches to identify the multiple cell types. These technically demanding steps require direction from established HuBMAP investigators as well as UConn faculty who are experts at performing assays in bone tissue sections. The Data Analysis Core translates the image files generated by these techniques into 3D cellular maps of the target tissue and transcriptome composition of each cell type. From those data files, the contextual molecular mapping program, TOPAS, examines the transcriptional and signaling pathways to impute how neighboring cells coordinate their activities to respond to mechanical loading and systemic factors that regulate skeletal health.

This team will also provide opportunities to transfer the histological technology to major academic skeletal research groups. Once the skeletal data becomes available, they will develop virtual workshops to inform the skeletal biology community of this valuable resource and how it can be utilized to unravel rare diseases affecting the skeleton. HuBMAP will be a transformational technology that every tissue centric group needs to incorporate. This team’s role is to ensure that the skeletal biology community is included in this new experimental platform, and that it is employed to solve the major genetic and therapeutic challenges affecting skeletal health.

Fast Facts
Project title: High resolution 3D mapping of cellular heterogeneity within articular cartilage
Organ specialty:Skeletal system
PI:David Rowe
Project Manager:Peter Maye
Assay Types:MERFISH
Grant number:1U54AR078664-01


 

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