作者: Fatima Valdes-Mora , Robert Salomon , Brian Gloss , Andrew MK. Law , Lesley Castillo
DOI: 10.1101/624890
关键词: Carcinogenesis 、 Cancer cell 、 Breast cancer 、 Cell 、 Biology 、 Cancer research 、 Mammary gland 、 Cancer 、 Cell type 、 Involution (medicine)
摘要: Abstract Single-cell RNA-seq has emerged as a powerful method to unravel heterogeneity of complex biological systems; this enabled in vivo characterization cell type compositions through unsupervised sampling and modelling transcriptional states single cells. Here we used the high-throughput microfluidic-based single-cell Drop-seq elucidate cellular composition functional diversity breast tumours during induction metastatic disease transgenic model related pregnancy-associated cancer (PABC). We characterised with unprecedented definition, how activation developmental programs associated pregnancy results acquisition an aggressive phenotype. show that cells are classified structure comparable lineages epithelial mammary gland hierarchy, revealing high dynamics plasticity progression. This progression program is orchestrated by alveolar milk secretory cells, conjunction types from tumour microenvironment (TME), including cancer-associated fibroblasts (CAFs), form multi-cellular process resembles aberrant involution. Finally, analysed interactome ecosystem define high-resolution landscape molecular pathways cell-to-cell communication underpins extra-cellular remodelling inflammation involution mimicry. In conclusion, our study recapitulates mechanisms have gone awry carcinogenesis PABC. provide large-scale allows understanding deep analysis key events result malignancy.