Abstract 76: Reprogramming of the preinvasive breast microenvironment identified by spatial nucleus barcoding

Abstract

Abstract Ductal-carcinoma-in-situ (DCIS) is the most common early-stage breast cancer and a non-obligate precursor to invasive breast cancer. However our understanding of the spatial microenvironment and the reprogramming of cell types in DCIS remains limited. To address this question, we developed a Spatial Nucleus Barcoding (SNuBar) method that utilizes a single oligonucleotide adaptor to preserve spatial information followed by performing single nucleus RNA sequencing. We validated the accuracy and scalability of SNuBar in cell lines and applied this method to investigate the spatial microenvironment of 4 normal breast tissues, 7 normal adjacent DCIS tissues, and 8 DCIS cancers. The analysis of single cells isolated from 596 macrodissected spatial regions identified 13 major cell types and 43 cell states, that co-localized in different combinations across four main topographic areas. Spatial analysis revealed that vascular and myoepithelial cells were reprogrammed in localized zones near the premalignant cells, while fibroblasts, T-cells and myeloid cells were reprogrammed across broader fields. Our data shows that many diverse cell types are reprogrammed in spatially-defined areas in the DCIS microenvironment, relative to the normal breast tissue regions. Citation Format: Kaile Wang, Zhenna Xiao, Yiyun Lin, Runmin Wei, Jie Ye, Rui Ye, Min Hu, Shanshan Bai, Emi Sei, Aatish Thennavan, Bora Lim, Andrew Futreal, Alastair Thompson, Savitri Krishnamurthy, Nicholas Navin. Reprogramming of the preinvasive breast microenvironment identified by spatial nucleus barcoding [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 76.