The Columbia University Senescence Tissue Mapping (CUSTMAP) Center comprises three scientific cores, which work together with the help of an Administrative Core. Human tissue samples characterized and collected through the Biospecimen Core (BIO) will be analyzed using the tools and techniques developed through the Biological Analysis Core (BAC) and Data Analysis Core (DAC), leading to detailed maps of senescent cells and their effects on human tissues at single-cell resolution.
Biospecimen Core (BIO)
The Biospecimen core is led by Andrew Teich, Ph.D., at Columbia University Irving Medical Center (CUIMC) and Dr. Colin Smith at The University of Edinburgh. We select tissue and biofluids from healthy individuals aged 20-80 years for high-quality molecular profiling. From the brain, we use the dorsolateral prefrontal cortex (DLPFC) and hippocampus. DLPFC is a region known to be susceptible to the effects of protein and vascular pathologies frequently associated with age-related diseases.
The BIO Core has two major avenues of tissue acquisition. First, historically banked samples are available through existing collaborations in the Edinburgh and New York Brain Banks. Using these two brain banks allows us to maximize diversity in age range capture, environmental exposures, and ethnicity. Secondly, these sites also have aligned methods and expertise for the prospective collection of targeted tissues to enable tissue collection of multiple samples from the same individual. The overall goals of the biospecimen core are to efficiently select subjects and tissues, establish a harmonized sample acquisition pipeline across two centers, and implement pathological characterization of samples to provide high-quality tissue to the Bioanalysis Core (BAC).
Biological Analysis Core (BAC)
Biological Analysis Core (BAC) is led by Hemali Phatnani, Ph.D., and generates spatially resolved, unbiased gene expression data in the brain and spinal cord from clinically assessed healthy young adults. The specific aims of the BAC are to generate Spatial Transcriptomic (ST) profiles across the lifespan, to generate single-nucleus RNA-seq (snRNA-seq) data to deconvolve ST profiles to the single-cell level across the lifespan from a subset of tissues, to generate Iterative Indirect Immunofluorescence Imaging (4i) proteomic profiles to assess the regional burden of senescence-associated molecular and cellular features, and finally, to validate cellular subpopulations and senescence markers across the lifespan. The ultimate goals of the BAC are to identify and validate a panel of robust senescence biomarkers for each cell type in our target tissues and their spatial context at the single-cell level and to assess the cell-autonomous and cell non-autonomous effects of senescent cells on the cellular composition and molecular signatures of the tissue microenvironment. We take advantage of the advanced technologies, workflows, and novel computational tools developed and established in the CUSTMAP Center, as well as our expertise and experience in generating multimodal omics data at the single-cell level in two target tissues: the brain and spinal cord.
Data Analysis Core (DAC)
The Data Analysis Core (DAC) is led by Vilas Menon, Ph.D., and plays a key role in all aspects of data processing and analysis, tissue mapping, and identification of markers of senescence, as well as data harmonization, coordination, and dissemination through the SenNet Consortium Data Coordination Center (CODCC). To achieve these goals, the DAC uses an integrative analysis approach to combine multi-modal data consisting of transcriptome-wide and targeted proteomics profiling in the tissues being examined across the adult human lifespan. This includes the three major data modalities described in the Biological Analysis Core: large-scale high-resolution Iterative Indirect Immunofluorescence Imaging (4i) data, genome-wide spatially resolved Spatial Transcriptomics (ST) data, and transcriptome-wide single-nucleus RNA-seq data. These three data modalities in concert allow for comprehensive (genome-wide) molecular characterization at single-cell resolution in space; any single experimental technique has not demonstrated this combination of attributes at scale currently in human tissue. By integrating these modalities using established processing and analysis workflows, the DAC will generate maps of known and novel senescence-associated markers, senescent cells, and the effects of senescent cells on their surroundings in each tissue type. To achieve these goals, the DAC implements modality-specific data processing workflows, followed by cross-modal data analysis; cross-individual map-building; and identification of novel, cell type-specific senescence signatures in the brain and spinal cord. This includes cross-referencing tissue-based signatures to data from ongoing efforts to identify senescence-related signatures in cerebrospinal fluid and blood, the primary biofluids associated with the central nervous system. Finally, the DAC works closely with the Administrative Core to interface with the SenNet CODCC to harmonize all aspects of data management and analysis with other consortium members.
Administrative Core (ADM)
The overall goals of the ADM core are to provide leadership and communication to other cores, establish a sample tracking system, and coordinate with the SenNet Consortium Organization and Data Coordination Center (CODCC) to plan the data sharing. ADM provides research and logistical oversight and facilitates communication among all center cores, as well as with the CODCC, the SenNet consortium at large, and the NIH. The ADM, composed of a director, all center PIs (MPIs), an executive committee (all core leadership), and support staff (program manager and systems analyst), oversees and coordinates the direction of three cores: Biospecimen Core (BIO), Biological Analysis Core (BAC), and Data Analysis Core (DAC). These cores contribute to the study of senescence in two primary tissue types, the brain and spinal cord, across the adult lifespan. The ADM has three main functions in support of the CUSTMAP Center: leadership, center coordination, and network coordination.