Evaluating diverse technologies for detecting and validating senescent cells in vivo

Dr. Duncan (Sub-PI) and Dr. Pavone (co-I) will be involved in Cellular Senescence Network: Technology Development and Application (UG3/UH3; RFA-RM-21-009)) being submitted by the Buck Institute on Aging: Evaluating diverse technologies for detecting and validating senescent cells in vivo. The work described below will take place at Northwestern University and is relevant to Pilot 2. The goals of Pilot 2 is to examine ovarian cellular senescence using a microphysiologic ex vivo tissue-on-a-chip platform. We will identify molecular signatures of ovarian senescent cells following drug-induced cellular senescence using single nucleus RNA sequencing (sNuc-seq) and chip cytometry-based Digital Spatial Profiling (DSP), and we will map these markers in ovaries across aging in human. We will then determine whether senolytics can abrogate human ovarian senescent cells (Goal 2) and investigate the relationship between cellular senescence and inter-tissue crosstalk (Goal 3). The team at Northwestern will: A. Provide the research team at the Buck Institute on Aging with already banked and de-identified human ovarian tissue specimens and matched demographic/clinical health data for downstream processing and analysis. The de-identified human tissues proposed for this work have already been collected through existing tissue repositories including the Northwestern University Reproductive Tissue Library (STU00072811) and the Oncofertility Consortium-National Physicians Cooperative Tissue Repository (STU00209753, assigned a determination of Not Human Research by the NU IRB). We will provide cryopreserved ovarian tissue samples from at least 10 individual participants and FFPE ovarian tissue samples from 60 participants in the form of an ovarian tissue microarray. Samples will be shared under a Material Transfer Agreement. B. Hold regularly scheduled videoconferences to update the research team and leadership on progress, review/analyze data, and discuss next steps. C. Participate in broader SenNet activities.