Single-Cell Chromatin Analysis of Mammary Gland Development Reveals Cell-State Transcriptional Regulators and Lineage Relationships

• Main Authors: Chi-Yeh Chung, Zhibo Ma, Christopher Dravis, Sebastian Preissl, Olivier Poirion, Gidsela Luna, Xiaomeng Hou, Rajshekhar R. Giraddi, Bing Ren, Geoffrey M. Wahl
• Format: Article
• Language: English
• Published: Elsevier 2019-10-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124719311519

Summary: Technological improvements enable single-cell epigenetic analyses of organ development. We reasoned that high-resolution single-cell chromatin accessibility mapping would provide needed insight into the epigenetic reprogramming and transcriptional regulators involved in normal mammary gland development. Here, we provide a single-cell resource of chromatin accessibility for murine mammary development from the peak of fetal mammary stem cell (fMaSC) functional activity in late embryogenesis to the differentiation of adult basal and luminal cells. We find that the chromatin landscape within individual cells predicts both gene accessibility and transcription factor activity. The ability of single-cell chromatin profiling to separate E18 fetal mammary cells into clusters exhibiting basal-like and luminal-like chromatin features is noteworthy. Such distinctions were not evident in analyses of droplet-based single-cell transcriptomic data. We present a web application as a scientific resource for facilitating future analyses of the gene regulatory networks involved in mammary development. : The ability to deconstruct complex tissues into their constituent cell states and identify molecular mechanisms involved in cell differentiation is enabling deeper understanding of normal development and disease. Chung et al. use snATAC-seq to agnostically determine the chromatin states correlated with cell-state changes during embryonic and postnatal mammary development. Keywords: single cell, snATAC-seq, ATAC-seq, chromatin profiling, mammary gland, mammary gland development, transcription factor dynamics, lineage relationships, pseudotime ordering, differentiation trajectory