Positional cues underlie cell fate specification during branching morphogenesis of the embryonic mammary epithelium
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PROVIDER: PRJNA866373 | ENA |
REPOSITORIES: ENA
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Project description:By single-cell RNA-sequencing across 4 stages of embryonic development, we reconstructed the differentiation trajectories of multipotent mammary stem cells towards basal and luminal fate. Our data revealed that MaSCs can already be resolved into distinct populations exhibiting lineage commitment at the time coinciding with the first sprouting events of mammary branching morphogenesis (E15.5). Through an interactive web tool for the visualization of gene expression across our developmental atlas, we provide novel molecular markers for committed and multipotent MaSCs, and define their spatial distribution within the developing tissue. Furthermore, we show that the mammary embryonic mesenchyme is composed of two spatially-restricted cell populations, representing the sub-epithelial and dermal mesenchyme.
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Project description:Branching morphogenesis of the mammary gland is driven by the highly motile terminal end bud (TEB) throughout pubertal development. The stem cell enriched, proliferative TEB branches as it invades the mammary fat pad to create a complex network of ducts. The gene expression programs specific to the TEB and the differentiated duct are poorly understood. We conducted a time course analysis of gene expression in the TEB and duct throughout branching morphogenesis. Additionally, we determined the gene regulatory networks coordinated by the Co-factor of LIM domains (CLIM/LDB) transcriptional regulators and determined an essential function for CLIMs in branching morphogenesis by maintaining basal mammary epithelial stem cells and promoting cell proliferation. We used laser capture microdissection to isolate TEB and duct cells throughout branching morphogenesis. We then profiled gene expression in these cells to determine gene regulatory networks involved in branching morphogenesis, and specifically those regulated by CLIM transcriptional regulators. Mouse mammary glands from 4, 6, 8, and 10 week old mice (early puberty through early adulthood) were used for laser capture microdissection of TEB and duct cells from WT and K14-DN-Clim transgenic mice. RNA was isolated (Qiagen) and hybridized to Affymetrix MouseGene 1.0 ST arrays. In addition, basal (CD29HiCD24+Lin-) and Luminal (CD29LoCD24+Lin-) cells were sorted and RNA collected for hybridization to Affymetrix MouseGene 1.0ST arrays.
2014-07-07 | E-GEOD-57724 | biostudies-arrayexpress
Project description:Branching morphogenesis of the mammary gland is driven by the highly motile terminal end bud (TEB) throughout pubertal development. The stem cell enriched, proliferative TEB branches as it invades the mammary fat pad to create a complex network of ducts. The gene expression programs specific to the TEB and the differentiated duct are poorly understood. We conducted a time course analysis of gene expression in the TEB and duct throughout branching morphogenesis. Additionally, we determined the gene regulatory networks coordinated by the Co-factor of LIM domains (CLIM/LDB) transcriptional regulators and determined an essential function for CLIMs in branching morphogenesis by maintaining basal mammary epithelial stem cells and promoting cell proliferation. We used laser capture microdissection to isolate TEB and duct cells throughout branching morphogenesis. We then profiled gene expression in these cells to determine gene regulatory networks involved in branching morphogenesis, and specifically those regulated by CLIM transcriptional regulators.
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Project description:Mechanical forces are increasingly recognized to regulate morphogenesis, but how this is accomplished in the context of the multiple tissues present within a developing organ remains unclear. Here we use bioengineered “microfluidic chest cavities” to precisely control the mechanical environment of the fetal lung. We show that transmural pressure controls airway branching morphogenesis and regulates the frequency of airway smooth muscle contraction. Next-generation sequencing analysis shows that lungs held at higher pressure are more mature than lungs held at lower pressure. Timelapse imaging reveals that branching events are synchronized across distant locations within the lung, and are preceded by long-duration waves of airway smooth muscle contraction. Higher transmural pressure decreases the interval between systemic smooth muscle contractions and increases the rate of morphogenesis of the airway epithelium. These data reveal that the mechanical properties of the microenvironment instruct crosstalk between tissues to control the rate of development of the embryonic lung.
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Project description:We report that a protein arginine methyltransferase Prmt and symmetric dimethylation at histone H arginine (HRsme) directly associates with chromatin of Bmp to suppress its transcription. Inactivation of Prmt in the lung epithelium results in halted branching morphogenesis, altered P-D airway patterning and neonatal lethality.
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