Biology subjects

Heijmans, N.

Publications and source records attributed to Heijmans, N..

3 recordsLinked to original sources

bioRxiv2025

GRHL and PGR control WNT4 expression in the mammary gland via 3D looping of conserved and species-specific enhancers

WNT4 is critical for epithelial side branching in the mammary gland. In both mice and humans, its expression is tightly regulated and restricted to hormone-responsive, mature luminal cells. Although generally assumed to act downstream of progesterone, the molecular mechanisms that control lineage-specific induction of WNT4 gene expression remain unknown. Here we functionally dissect the cis-acting enhancer network and spatiotemporal transcriptional mechanisms that regulate WNT4 expression in the mouse mammary gland and the human breast. We identify Grainyhead-like (GRHL) proteins as luminal-specific pioneer factors that bind to a conserved distal chromatin hub. The progesterone receptor (PGR) binds to different cis-acting elements that contact the hub via 3D chromatin looping to induce WNT4 expression. More generally, this model explains how the interplay between endocrine signaling and dynamic molecular interactions at the physical chromatin level can be translated into robust gene expression patterns on the tissue scale. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=102 SRC="FIGDIR/small/648333v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@ddca48org.highwire.dtl.DTLVardef@10b3d69org.highwire.dtl.DTLVardef@ecea45org.highwire.dtl.DTLVardef@86d00_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2024

Transcriptomic analysis of pubertal and adult virgin mouse mammary epithelial and stromal cell populations

Conflicting data exist as to how mammary epithelial cell proliferation changes during the reproductive cycle. To study the effect of endogenous hormone fluctuations on gene expression in the mouse mammary gland, we performed bulk RNAseq analyses of epithelial and stromal cell populations that were isolated either during puberty or at different stages of the adult virgin estrous cycle. Our data confirm prior findings that proliferative changes do not occur in every mouse in every cycle. We also show that during the estrous cycle the main gene expression changes occur in adipocytes and other stromal cells. Finally, we present a comprehensive overview of the Wnt gene expression landscape in different mammary gland cell types in pubertal and adult mice. This work contributes to understanding the effects of physiological hormone fluctuations and locally produced signaling molecules on gene expression changes in the mammary gland during the reproductive cycle and should be a useful resource for future studies investigating gene expression patterns in different cell types across different developmental timepoints.

developmental biology↗

bioRxiv2020

How to use online tools to generate new hypotheses for mammary gland biology research: a case study for Wnt7b

An increasing number of -omics datasets, generated by labs all across the world, are becoming available. They contain a wealth of data that are largely unexplored. Not every scientist, however, will have access to the required resources and expertise to analyze such data from scratch. Luckily, a growing number of investigators is dedicating their time and effort to the development of user friendly, online applications that allow researchers to use and investigate these datasets. Here, we will illustrate the usefulness of such an approach. Using regulation of Wnt7b as an example, we will highlight a selection of accessible tools and resources that are available to researchers in the area of mammary gland biology. We show how they can be used for in silico analyses of gene regulatory mechanisms, resulting in new hypotheses and providing leads for experimental follow up. We also call out to the mammary gland community to join forces in a coordinated effort to generate and share additional tissue-specific -omics datasets and thereby expand the in silico toolbox.

developmental biology↗