Biology subjects

Wisniewska, K.

Publications and source records attributed to Wisniewska, K..

5 recordsLinked to original sources

bioRxiv2026

Range wide analysis of genetic diversity and structure gives insights into Rosa gallica L. evolutionary history

Rosa gallica L., the French rose, is a perennial, tetraploid, heterozygous species that naturally propagates by seed and sucker. It occurs in the wild, primarily in Europe, and also exists as cultivated varieties. R. gallica cultivars were extensively bred and cultivated in France at the beginning of the 19th century. Although several hypotheses have been proposed regarding the species expansion based on historical records, none have been assessed using molecular data. Indeed, its genetic diversity has so far been investigated only at local or regional scales, hindering the identification of the evolutionary factors shaping its present-day distribution. Using 29 sequenced microsatellites, we genotyped a comprehensive sample of 1618 individuals, including wild R. gallica from 219 sites across the species range, rose cultivars, and specimens from other Rosa species. We then detected clonal lineages and characterized the range-wide genetic diversity and structure, aiming to disentangle the roles of natural and human factors in shaping the distribution of R. gallica, with particular focus on France. French diversity appears particularly structured compared to the rest of the range, suggesting multiple origins within France. Populations in South Alps, Central Eastern Europe, and Eastern France appear to have recolonized naturally from a single southern glacial refugium. In contrast, populations in the western part of France likely resulted from more recent natural or human-mediated dispersal. Finally, clonal lineages containing both wild and cultivated individuals were predominantly found in France, highlighting the role of human-mediated dispersal in 28 of the 98 French sites studied. These findings show that the present-day natural range of R. gallica was shaped primarily by post-glacial recolonization, but also reveal a contribution of human activities to its recent dispersal, particularly in France, where cultivated varieties were intensively bred and exchanged.

genetics↗

bioRxiv2024

Defining the Regulatory Logic of Breast Cancer Using Single-Cell Epigenetic and Transcriptome Profiling

Annotation of the cis-regulatory elements that drive transcriptional dysregulation in cancer cells is critical to improving our understanding of tumor biology. Herein, we present a compendium of matched chromatin accessibility (scATAC-seq) and transcriptome (scRNA-seq) profiles at single-cell resolution from human breast tumors and healthy mammary tissues processed immediately following surgical resection. We identify the most likely cell-of-origin for luminal breast tumors and basal breast tumors and then introduce a novel methodology that implements linear mixed-effects models to systematically quantify associations between regions of chromatin accessibility (i.e. regulatory elements) and gene expression in malignant cells versus normal mammary epithelial cells. These data unveil regulatory elements with that switch from silencers of gene expression in normal cells to enhancers of gene expression in cancer cells, leading to the upregulation of clinically relevant oncogenes. To translate the utility of this dataset into tractable models, we generated matched scATAC-seq and scRNA-seq profiles for breast cancer cell lines, revealing, for each subtype, a conserved oncogenic gene expression program between in vitro and in vivo cells. Together, this work highlights the importance of non-coding regulatory mechanisms that underlie oncogenic processes and the ability of single-cell multi-omics to define the regulatory logic of BC cells at single-cell resolution.

genomics↗

bioRxiv2023

Tamoxifen Response at Single Cell Resolution in Estrogen Receptor-Positive Primary Human Breast Tumors

In ER+/HER2- breast cancer, multiple measures of intra-tumor heterogeneity are associated with worse response to endocrine therapy. To investigate heterogeneity in response to treatment, we developed an operating room-to-laboratory pipeline for the collection of live human tumors and normal breast specimens immediately after surgical resection for processing into single-cell workflows for experimentation and genomic analyses. We demonstrate differences in tamoxifen response by cell type and identify distinctly responsive and resistant subpopulations within the malignant cell compartment of human tumors. Tamoxifen resistance signatures from 3 distinct resistant subpopulations are prognostic in large cohorts of ER+ breast cancer patients and enriched in endocrine therapy resistant tumors. This novel ex vivo model system now provides a foundation to define responsive and resistant sub-populations within heterogeneous tumors, to develop precise single cell-based predictors of response to therapy, and to identify genes and pathways driving resistance to therapy.

cancer biology↗

bioRxiv2022

Single-Cell Transcriptional and Epigenetic Profiles of Male Breast Cancer Nominate Salient Cancer-Specific Enhancers

Male breast cancer represents about 1% of all breast cancer diagnoses and, although there are some similarities between male and female breast cancer, the paucity of data available on male breast cancer makes it difficult to establish targeted therapies. To date, most male breast cancers (MBC) are treated according to protocols established for female breast cancer (FBC). Thus, defining the transcriptional and epigenetic landscape of MBC with improved resolution is critical for developing better avenues for therapeutic intervention. In this study, we present matched transcriptional (scRNA-seq) and epigenetic (scATAC-seq) profiles at single-cell resolution of two treatment naive MBC tumors processed immediately after surgical resection. These data enable the detection of differentially expressed genes between male and female breast tumors across immune, stromal, and malignant cell types, to highlight several genes that may have therapeutic implications. Notably, MYC target genes and mTORC1 signaling genes were significantly upregulated in the malignant cells of MBC compared to the female counterparts. To understand how the regulatory landscape of MBC give rise to these male-specific gene expression patterns, we leveraged the scATAC-seq data to systematically link changes in chromatin accessibility to changes in gene expression within each cell type. We observed cancer-specific rewiring of several salient enhancers and posit that these enhancers have a higher regulatory load than lineage specific enhancers. We highlight two examples of previously unannotated cancer-cell specific enhancers of ANXA2 and PRDX4 gene expression and show evidence for super-enhancer regulation of LAMB3 and CD47 in male breast cancer cells. Overall, this dataset annotates clinically relevant regulatory networks in male breast tumors, providing a useful resource that expands our current understanding of the gene expression programs that underlie the biology of MBC.

genomics↗

bioRxiv2022

A multi-omic dissection of super-enhancer driven oncogenic gene expression programs in ovarian cancer

The human genome contains regulatory elements, such as enhancers, that are often rewired by cancer cells for the activation of genes that promote tumorigenesis and resistance to therapy. This is especially true for cancers that have little or no known driver mutations within protein coding genes, such as ovarian cancer. Herein, we have utilized an integrated set of genomic and epigenomic datasets to identify clinically relevant super-enhancers that are preferentially amplified in ovarian cancer patients. We have systematically probed the top 86 super-enhancers, using CRISPR-interference and CRISPR-deletion assays coupled to RNA-sequencing, to nominate two salient super-enhancers that drive proliferation and migration of cancer cells. Utilizing Hi-C, we constructed chromatin interaction maps that enabled the annotation of direct target genes for these super-enhancers and later confirmed their activity specifically within the cancer cell compartment of human tumors using single-cell genomics data. Together, our multi-omic approach has examined a number of fundamental questions about how regulatory information encoded into super-enhancers drives gene expression networks that underlie the biology of ovarian cancer.

cancer biology↗