WU-SN-TMC Bio-Analysis Core

Biological Analysis Core Summary/Abstract
Senescence is implicated in many human diseases and the elimination of senescent cells in model organisms
slows, and in some cases reverses many diseases. These findings raise hope that a detailed mechanistic
understanding of senescence will lead to novel therapies to treat human disease. Despite the importance of
cellular senescence, we lack robust methods to identify, isolate, and manipulate senescent cells. New
approaches and technologies position our team to comprehensively identify senescent cells. This, in turn, will
enable in-depth analyses of biomarkers, spatial distribution, behavior, and function of senescent cells across
human tissues and time in a high throughput manner. The primary goal for the Biological Analysis Core (BAC)
within Washington University Senescence Mapping Center (WU-SN-TMC) is to generate multi-omics and
imaging data to build high resolution, multi-dimensional atlases of cellular senescence across tissue types and
lifespan to facilitate basic and translational research. Although senescent cells are tracked by several known
markers, it is increasingly clear that not all senescent cells express the same set of markers and the usefulness
of individual senescent markers may be limited. Static universal tissue agnostic senescence markers may not
exist. Instead, there are likely dynamic senescence signatures (gene expression patterns anchored by frequent,
but unobligated presence of some of the “known” markers and others yet to be identified), that may differ with
cell type, age, and environmental stimuli. We propose using cutting edge enabling technologies at necessary
scale, depth, and resolution to identify such signatures while mapping senescent cells in various tissue
environments at different ages. We will map senescent cells and their associated phenotypes in four tissues
(bone marrow, breast, liver, and colon), chosen for their clinical importance, diversity, relevance to
senescence, and availability. We will utilize the highly successful infrastructure we have developed for several
large-scale projects as a springboard, combined with in-house expertise in senescence research, to generate
cellular senescence atlases with transcriptome-wide coverage, single cell resolution, and spatial registration.
We will use our experience in single cell omics to establish a comprehensive epigenetic and transcriptomic
landscape in targeted tissues. We will add the spatial dimension to build 2D and 3D molecular atlases by
incorporating spatial transcriptomics, CODEX, and light sheet microscopy. We will also use proteomics to study
the biomarkers and secretome of senescent cells. To validate our results, we will use established and newly
developed mouse models to track senescent cells at different ages with or without perturbations. These studies
will allow us to improve detection methods for senescent cells and validate biomarker signatures identified in
human studies. BAC will work closely with the other Cores within WU-SN-TMC to produce multi-dimensional
molecular and cellular senescence tissue atlases at unprecedented cellular resolution and gene coverage with
the highest efficiency possible.

Grant Number: 5U54AG075934-05
NIH Institute/Center: NIH
Principal Investigator: FENG CHEN