Single-cell morphology encodes functional subtypes of senescence in aging human dermal fibroblasts

Cellular senescence, a hallmark of aging, reveals context-dependent phenotypes across multiple biological length scales. Despite its mechanistic importance, identifying and characterizing senescence across cell populations is challenging. Using primary dermal fibroblasts, we combined single-cell imaging, machine learning, several induced senescence conditions, and multiple protein biomarkers to define functional senescence subtypes. Single-cell morphology analysis revealed eleven distinct morphology clusters. Among these, we identified three as bona-fide senescence subtypes (C7, C10, C11), with C10 exhibiting the strongest age-dependence within an aging cohort. Additionally, we observed that a donor’s senescence burden and subtype-composition were indicative of susceptibility to doxorubicin-induced senescence. Functional analysis revealed subtype-dependent responses to senotherapies, with C7 being most responsive to Dasatinib + Quercetin. Our single-cell analysis framework, SenSCOUT, en..., , , # Single-cell morphology encodes functional subtypes of senescence in aging human dermal fibroblasts

\[SENescent Subtype Classifier based on Observable Unique phenoTypes]

This repository contains the data and code associated with the study titled \"Single-cell morphology encodes functional subtypes of senescence in aging human dermal fibroblasts,\" available at [https://www.biorxiv.org/content/10.1101/2023.05.17.541204v1](https://www.biorxiv.org/content/10.1101/2023.05.17.541204v1).

Paper: [https://www.biorxiv.org/content/10.1101/2023.05.17.541204v1](https://www.biorxiv.org/content/10.1101/2023.05.17.541204v1)

Use Guide:

Manuscript and Figures Folder
Contains paper and associated figures
Codes Folder
Contains example workflow
Preprocessing delineates log normalization and standard scaling of morphological data
Senescence UMAP_KMEANS describes 2D dimensionality reduction and identification of KMEANS clusters
Biomarker Imputation Platform describes imputation platform using morphology ...,