Use of a Novel Embryonic Mammary Stem Cell Gene Signature to Improve Human Breast Cancer Diagnostics and Therapeutic Decision Making
Technical Report,30 Sep 2012,29 Sep 2015
The Salk Institute for Biological Studies La Jolla United States
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Our major goals have remained the same as described in the previous report. In Aim 1, we ascertained Fetal Mammary Stem Cell fMaSC signatures to determine whether they chemotherapy response and metastasis in different breast cancer intrinsic subtypes AIM1. Aim 2 developed single cell sequencing protocols to identify gene expression programs that correlate with entry into and exit from the mammary stem cell state. The data obtained should enable us to 1 better categorize distinct cell types within the fMaSC population, 2 identify biomarkers for prospective stem cell purification and in situ localization, and 3 identify candidate stem cell regulatory pathways that should reveal therapeutic targets and improved prognosticators and response biomarkers. Over the past year we published two papers using the fMaSC signatures to identify expression features correlating with chemotherapeutic response of human breast cancer patients. We obtained improved fMaSC profiles through RNA Sequencing and validated our single cell RNA Sequencing and analytical pipeline over multiple developmental time points. We found shared co-expression of genes in fMaSCs and certain breast cancers. The single cell profiles also provide candidate biomarkers for fMaSC-like cells in tumors. The two publications resulting from this Idea Award Expansion largely complete the proposed Aims and provide the bases for substantial future work funded by other sources.