Raths, F. | Search bioRxiv

bioRxiv2022

The molecular consequences of androgen activity in the human breast

The mammary gland has been extensively studied for estrogen and progesterone reactivity, but the molecular effects of androgen in the breast remain largely unexplored. Transgender men are recorded female at birth but identify as male and may undergo gender-affirming androgen therapy to align their physical characteristics and gender identity. Here we perform single cell resolution transcriptome, chromatin, and spatial profiling of androgen treated breasts from transgender men. We find male-biased androgen receptor gene targets are upregulated in cells expressing androgen receptor, and that paracrine signaling drives sex-relevant changes in other cell types. We observe an altered epithelium, shifts in immune populations, and a reduction of capillary vasculature. Finally, we find evidence of the metabolic impact of androgen and identify a gene regulatory network driving androgen-directed fat loss. This work elucidates the molecular consequences of androgen in the human breast at single cell resolution.

genomics↗

bioRxiv2018

SmartCodes : functionalized barcodes that enable targeted retrieval of clonal lineages from a heterogeneous population

Molecular barcoding has provided means to link genotype to phenotype, to individuate cells in single-cell analyses, to enable the tracking of evolving lineages, and to facilitate the analysis of complex mixtures containing phenotypically distinct lineages. To date, all existing approaches enable retrospective associations to be made between characteristics and the lineage harbouring them, but provide no path toward isolating or manipulating those lineages within the complex mixture. Here, we describe a strategy for creating functionalized barcodes that enable straightforward manipulation of lineages within complex populations of cells, either marking and retrieval of selected lineages, or modification of their phenotype within the population, including their elimination. These \"SmartCodes\" rely on a simple CRISPR-based, molecular barcode reader that can switch measurable, or selectable markers, on or off in a binary fashion. While this approach could have broad impact, we envision initial approaches to the study of tumour heterogeneity, focused on issues of tumour progression, metastasis, and drug resistance.

molecular biology↗