Single cell transcriptomic heterogeneity in invasive ductal and lobular breast cancer cells

Invasive lobular breast carcinoma (ILC), one of the major breast cancer histological subtypes, exhibits unique clinical and molecular features compared to the other well-studied ductal cancer subtype (IDC). The pathognomonic feature of ILC is loss of E-cadherin, mainly due to inactivating mutations within the CDH1 gene, but the extent of contribution of this genetic alteration to ILC-specific molecular characteristics remains largely understudied. To profile these features transcriptionally, we conducted single cell RNA sequencing on a panel of IDC and ILC cell lines, as well as an IDC cell line (T47D) with CRISPR-mediated knock out (KO) of CDH1. Inspection of intra-cell line heterogeneity illustrated genetically and transcriptionally distinct subpopulations in multiple cell lines and highlighted rare populations of cells with long latency and an apoptosis-related signature indicative of dormancy. Investigation of CDH1 KO-induced alterations showed transcriptomic membranous systems remodeling, elevated regulon activation resemblance of T47D CDH1 KO cells to ILCs, and suggests IRF1 as a major regulator of the pro-apoptotic and anti-proliferative feature of ILCs. scRNA-seq data of a mixture of 9 groups of cells of 8 cell lines: MCF7 (MCF7 wild type and MCF7 with ESR1 Y537S mutation), T47D wild type, T47D with CDH1 knock out (CRISPR), MDA-MB-134-VI, SUM44-PE, BCK4, MCF10A, and HEK293; using 10X Genomics 3' Chromium v3.0 and Illumina NovaSeq 6000 System.