A single-cell atlas enables mapping of homeostatic cellular shifts in the adult human breast

A.D.R. performed the majority of the bioinformatic analysis and interpretation of the data. S.P. contributed to the study design, sample processing, analysis and interpretation of the data. J.S. contributed to the sample processing. D.J.K. and P.H. contributed to the data processing, batch correction and cell cluster identification. A.S. contributed to the design of the sample batches and contributed to the analysis of the raw data. A.J.T. contributed to the analysis of the data and Figure design. L.J.P. performed the immune histochemistry validations. K.H. assisted A.D.R. with the inferCNV analysis and interpretation. P.H. assisted with the subclustering of immune cells and scVI integration analysis. A.Q.S. performed the immunofluorescence quantification. K.K. performed all the scRNA-seq library preparation and sequencing. R.B.M., I.G., J.J.G., V.S. and J.L.J. provided the human tissues and the metadata from the 55 donors. A.D.R., S.P., J.C.M. and W.T.K. wrote the paper. J.C.M. and W.T.K. conceptualized and supervised the study.Peer reviewe

Dynamic Biobanking for Advancing Breast Cancer Research

Longitudinal patient biospecimens and data advance breast cancer research through enabling precision medicine approaches for identifying risk, early diagnosis, improved disease management and targeted therapy. Cancer biobanks must evolve to provide not only access to high-quality annotated biospecimens and rich associated data, but also the tools required to harness these data. We present the Breast Cancer Now Tissue Bank centre at the Barts Cancer Institute as an exemplar of a dynamic biobanking ecosystem that hosts and links longitudinal biospecimens and multimodal data including electronic health records, genomic and imaging data, offered alongside integrated data sharing and analytics tools. We demonstrate how such an ecosystem can inform precision medicine efforts in breast cancer research

A single-cell atlas enables mapping of homeostatic cellular shifts in the adult human breast.

Acknowledgements: We thank the staff at the Cambridge NIHR BRC Cell Phenotyping Hub and the Genomic and Histopathology Core at the CRUK Cambridge Institute for their constant support and assistance and S. Westermann for designing the schematic in Fig. 1. We acknowledge the role of the Breast Cancer Now Tissue Bank in collecting and making available the samples used in the generation of this publication and all the patients who donated. This study was primarily funded by an MRC project grant (MR/S036059/1) and supported by BBSRC project grant (BB/S006745/1), Breast Cancer Now project grant (2017MayPR907), CRUK career establishment award (17348) and CRUK programme foundation award (DCRPGF\100010) to W.T.K. and core funding from EMBL and CRUK (C9545/A29580) to J.C.M.Here we use single-cell RNA sequencing to compile a human breast cell atlas assembled from 55 donors that had undergone reduction mammoplasties or risk reduction mastectomies. From more than 800,000 cells we identified 41 cell subclusters across the epithelial, immune and stromal compartments. The contribution of these different clusters varied according to the natural history of the tissue. Age, parity and germline mutations, known to modulate the risk of developing breast cancer, affected the homeostatic cellular state of the breast in different ways. We found that immune cells from BRCA1 or BRCA2 carriers had a distinct gene expression signature indicative of potential immune exhaustion, which was validated by immunohistochemistry. This suggests that immune-escape mechanisms could manifest in non-cancerous tissues very early during tumor initiation. This atlas is a rich resource that can be used to inform novel approaches for early detection and prevention of breast cancer.This study was primarily funded by an MRC project grant (MR/S036059/1), CRUK career establishment award (17348) and CRUK programme foundation award (DCRPGF\100010) to WTK and core funding from EMBL and CRUK (C9545/A29580) to JCM

A single-cell atlas enables mapping of homeostatic cellular shifts in the adult human breast.

Here we use single-cell RNA sequencing to compile a human breast cell atlas assembled from 55 donors that had undergone reduction mammoplasties or risk reduction mastectomies. From more than 800,000 cells we identified 41 cell subclusters across the epithelial, immune and stromal compartments. The contribution of these different clusters varied according to the natural history of the tissue. Age, parity and germline mutations, known to modulate the risk of developing breast cancer, affected the homeostatic cellular state of the breast in different ways. We found that immune cells from BRCA1 or BRCA2 carriers had a distinct gene expression signature indicative of potential immune exhaustion, which was validated by immunohistochemistry. This suggests that immune-escape mechanisms could manifest in non-cancerous tissues very early during tumor initiation. This atlas is a rich resource that can be used to inform novel approaches for early detection and prevention of breast cancer.This study was primarily funded by an MRC project grant (MR/S036059/1), CRUK career establishment award (17348) and CRUK programme foundation award (DCRPGF\100010) to WTK and core funding from EMBL and CRUK (C9545/A29580) to JCM