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Acta Obstetricia Et Gynecologica... Nov 2015The aim of this article is to review the physiology of progesterone and focus on its physiological actions on tissues such as endometrium, uterus, mammary gland,... (Review)
Review
INTRODUCTION
The aim of this article is to review the physiology of progesterone and focus on its physiological actions on tissues such as endometrium, uterus, mammary gland, cardiovascular system, central nervous system and bones. In the last decades, the interest of researchers has focused on the role of progesterone in genomic and non-genomic receptor mechanisms.
MATERIALS AND METHODS
We searched PubMed up to December 2014 for publications on progesterone/steroidogenesis.
RESULTS AND CONCLUSIONS
A better understanding of the biological genomic and non-genomic receptor mechanisms could enable us in the near future to obtain a more comprehensive knowledge of the safety and efficacy of this agent during hormone replacement therapy (natural progesterone), in vitro fertilization (water-soluble subcutaneous progesterone), in traumatic brain injury, Alzheimer's disease and diabetic neuropathy, even though further clinical studies are needed to prove its usefulness.
Topics: Cell Membrane; Cell Nucleus; Central Nervous System; Embryo Implantation; Endometrium; Female; Humans; Mammary Glands, Human; Menstrual Cycle; Osteoporosis; Progesterone; Receptors, Progesterone
PubMed: 26358238
DOI: 10.1111/aogs.12771 -
Current Opinion in Cell Biology Oct 2020The mammary gland is a highly dynamic tissue that undergoes repeated cycles of growth and involution during pregnancy and menstruation. It is also the site from which... (Review)
Review
The mammary gland is a highly dynamic tissue that undergoes repeated cycles of growth and involution during pregnancy and menstruation. It is also the site from which breast cancers emerge. Organoids provide an in vitro model that preserves several of the cellular, structural, and microenvironmental features that dictate mammary gland function in vivo and have greatly advanced our understanding of glandular biology. Their tractability for genetic manipulation, live imaging, and high throughput screening have facilitated investigation into the mechanisms of glandular morphogenesis, structural maintenance, tumor progression, and invasion. Opportunities remain to enhance cellular and structural complexity of mammary organoid models, including incorporating additional cell types and hormone signaling.
Topics: Animals; Breast Neoplasms; Female; Humans; Mammary Glands, Animal; Mammary Glands, Human; Models, Biological; Morphogenesis; Organoids
PubMed: 32535255
DOI: 10.1016/j.ceb.2020.05.003 -
Seminars in Cell & Developmental Biology Jun 2021Our understanding of the molecular events underpinning the development of mammalian organ systems has been increasing rapidly in recent years. With the advent of new and... (Review)
Review
Our understanding of the molecular events underpinning the development of mammalian organ systems has been increasing rapidly in recent years. With the advent of new and improved next-generation sequencing methods, we are now able to dig deeper than ever before into the genomic and epigenomic events that play critical roles in determining the fates of stem and progenitor cells during the development of an embryo into an adult. In this review, we detail and discuss the genes and pathways that are involved in mammary gland development, from embryogenesis, through maturation into an adult gland, to the role of pregnancy signals in directing the terminal maturation of the mammary gland into a milk producing organ that can nurture the offspring. We also provide an overview of the latest research in the single-cell genomics of mammary gland development, which may help us to understand the lineage commitment of mammary stem cells (MaSCs) into luminal or basal epithelial cells that constitute the mammary gland. Finally, we summarize the use of 3D organoid cultures as a model system to study the molecular events during mammary gland development. Our increased investigation of the molecular requirements for normal mammary gland development will advance the discovery of targets to predict breast cancer risk and the development of new breast cancer therapies.
Topics: Animals; Cell Differentiation; Epithelial Cells; Female; Humans; Mammary Glands, Animal; Mammary Glands, Human
PubMed: 33082117
DOI: 10.1016/j.semcdb.2020.09.014 -
Physiological Reviews Apr 2020The mammary gland is a highly dynamic organ that undergoes profound changes within its epithelium during puberty and the reproductive cycle. These changes are fueled by... (Review)
Review
The mammary gland is a highly dynamic organ that undergoes profound changes within its epithelium during puberty and the reproductive cycle. These changes are fueled by dedicated stem and progenitor cells. Both short- and long-lived lineage-restricted progenitors have been identified in adult tissue as well as a small pool of multipotent mammary stem cells (MaSCs), reflecting intrinsic complexity within the epithelial hierarchy. While unipotent progenitor cells predominantly execute day-to-day homeostasis and postnatal morphogenesis during puberty and pregnancy, multipotent MaSCs have been implicated in coordinating alveologenesis and long-term ductal maintenance. Nonetheless, the multipotency of stem cells in the adult remains controversial. The advent of large-scale single-cell molecular profiling has revealed striking changes in the gene expression landscape through ontogeny and the presence of transient intermediate populations. An increasing number of lineage cell-fate determination factors and potential niche regulators have now been mapped along the hierarchy, with many implicated in breast carcinogenesis. The emerging diversity among stem and progenitor populations of the mammary epithelium is likely to underpin the heterogeneity that characterizes breast cancer.
Topics: Animals; Breast Neoplasms; Cell Differentiation; Cell Lineage; Cell Transformation, Neoplastic; Female; Gene Expression Regulation, Developmental; Humans; Mammary Glands, Animal; Mammary Glands, Human; Morphogenesis; Neoplastic Stem Cells; Phenotype; Signal Transduction; Stem Cells; Transcription Factors; Tumor Microenvironment
PubMed: 31539305
DOI: 10.1152/physrev.00040.2018 -
The EMBO Journal Jun 2021To examine global changes in breast heterogeneity across different states, we determined the single-cell transcriptomes of > 340,000 cells encompassing normal breast,...
To examine global changes in breast heterogeneity across different states, we determined the single-cell transcriptomes of > 340,000 cells encompassing normal breast, preneoplastic BRCA1 tissue, the major breast cancer subtypes, and pairs of tumors and involved lymph nodes. Elucidation of the normal breast microenvironment revealed striking changes in the stroma of post-menopausal women. Single-cell profiling of 34 treatment-naive primary tumors, including estrogen receptor (ER) , HER2 , and triple-negative breast cancers, revealed comparable diversity among cancer cells and a discrete subset of cycling cells. The transcriptomes of preneoplastic BRCA1 tissue versus tumors highlighted global changes in the immune microenvironment. Within the tumor immune landscape, proliferative CD8 T cells characterized triple-negative and HER2 cancers but not ER tumors, while all subtypes comprised cycling tumor-associated macrophages, thus invoking potentially different immunotherapy targets. Copy number analysis of paired ER tumors and lymph nodes indicated seeding by genetically distinct clones or mass migration of primary tumor cells into axillary lymph nodes. This large-scale integration of patient samples provides a high-resolution map of cell diversity in normal and cancerous human breast.
Topics: Breast Neoplasms; CD8-Positive T-Lymphocytes; Carcinogenesis; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genetic Heterogeneity; Humans; Mammary Glands, Human; RNA-Seq; Single-Cell Analysis; Tumor Microenvironment
PubMed: 33950524
DOI: 10.15252/embj.2020107333 -
Neoplasia (New York, N.Y.) Dec 2020The cellular heterogeneity of breast cancers still represents a major therapeutic challenge. The latest genomic studies have classified breast cancers in distinct... (Review)
Review
The cellular heterogeneity of breast cancers still represents a major therapeutic challenge. The latest genomic studies have classified breast cancers in distinct clusters to inform the therapeutic approaches and predict clinical outcomes. The mammary epithelium is composed of luminal and basal cells, and this seemingly hierarchical organization is dependent on various stem cells and progenitors populating the mammary gland. Some cancer cells are conceptually similar to the stem cells as they can self-renew and generate bulk populations of nontumorigenic cells. Two models have been proposed to explain the cell of origin of breast cancer and involve either the reprogramming of differentiated mammary cells or the dysregulation of mammary stem cells or progenitors. Both hypotheses are not exclusive and imply the accumulation of independent mutational events. Cancer stem cells have been isolated from breast tumors and implicated in the development, metastasis, and recurrence of breast cancers. Recent advances in single-cell sequencing help deciphering the clonal evolution within each breast tumor. Still, few clinical trials have been focused on these specific cancer cell populations.
Topics: Animals; Breast Neoplasms; Disease Models, Animal; Disease Susceptibility; Female; Humans; Incidence; Mammary Glands, Human; Mice; Neoplasm Staging; Neoplastic Stem Cells; Risk Assessment; Stem Cells
PubMed: 33142233
DOI: 10.1016/j.neo.2020.09.009 -
Nature Communications Apr 2020Recently, organoid technology has been used to generate a large repository of breast cancer organoids. Here we present an extensive evaluation of the ability of organoid...
Recently, organoid technology has been used to generate a large repository of breast cancer organoids. Here we present an extensive evaluation of the ability of organoid culture technology to preserve complex stem/progenitor and differentiated cell types via long-term propagation of normal human mammary tissues. Basal/stem and luminal progenitor cells can differentiate in culture to generate mature basal and luminal cell types, including ER+ cells that have been challenging to maintain in culture. Cells associated with increased cancer risk can also be propagated. Single-cell analyses of matched organoid cultures and native tissues by mass cytometry for 38 markers provide a higher resolution representation of the multiple mammary epithelial cell types in the organoids, and demonstrate that protein expression patterns of the tissue of origin can be preserved in culture. These studies indicate that organoid cultures provide a valuable platform for studies of mammary differentiation, transformation, and breast cancer risk.
Topics: Adult; BRCA1 Protein; Breast Neoplasms; Cell Culture Techniques; Cell Differentiation; Cell Lineage; Epidermal Growth Factor; ErbB Receptors; Female; Humans; Mammary Glands, Human; Middle Aged; Organoids; Single-Cell Analysis; Stem Cells; Transforming Growth Factor beta; Young Adult; p38 Mitogen-Activated Protein Kinases
PubMed: 32249764
DOI: 10.1038/s41467-020-15548-7 -
Seminars in Cell & Developmental Biology Jun 2021Embryonic mammary gland development involves the formation of mammary placodes, invagination of flask-shaped mammary buds and development of miniature bi-layered ductal... (Review)
Review
Embryonic mammary gland development involves the formation of mammary placodes, invagination of flask-shaped mammary buds and development of miniature bi-layered ductal trees. Currently there is a good understanding of the factors that contribute to ectodermal cell movements to create these appendages and of pathways that lead to mammary specification and commitment. Gene expression profiles of early bipotent mammary stem cells populations as well as cell surface proteins and transcription factors that promote the emergence of unipotent progenitors have been identified. Analyses of these populations has illuminated not only embryonic mammary development, but highlighted parallel processes in breast cancer. Here we provide an overview of the highly conserved pathways that shape the embryonic mammary gland. Understanding the dynamic signaling events that occur during normal mammary development holds considerable promise to advance attempts to eliminate cancer by restoring differentiative signals.
Topics: Animals; Disease Models, Animal; Female; Humans; Mammary Glands, Animal; Mammary Glands, Human; Mice
PubMed: 33472760
DOI: 10.1016/j.semcdb.2020.12.012 -
Journal of Mammary Gland Biology and... Sep 2021
Topics: Animals; Breast Neoplasms; Editorial Policies; Female; Humans; Mammary Glands, Animal; Mammary Glands, Human; Mammary Neoplasms, Animal; Periodicals as Topic
PubMed: 34648096
DOI: 10.1007/s10911-021-09500-8 -
Nature Cell Biology Feb 2022Metabolic characteristics of adult stem cells are distinct from their differentiated progeny, and cellular metabolism is emerging as a potential driver of cell fate...
Metabolic characteristics of adult stem cells are distinct from their differentiated progeny, and cellular metabolism is emerging as a potential driver of cell fate conversions. How these metabolic features are established remains unclear. Here we identified inherited metabolism imposed by functionally distinct mitochondrial age-classes as a fate determinant in asymmetric division of epithelial stem-like cells. While chronologically old mitochondria support oxidative respiration, the electron transport chain of new organelles is proteomically immature and they respire less. After cell division, selectively segregated mitochondrial age-classes elicit a metabolic bias in progeny cells, with oxidative energy metabolism promoting differentiation in cells that inherit old mitochondria. Cells that inherit newly synthesized mitochondria with low levels of Rieske iron-sulfur polypeptide 1 have a higher pentose phosphate pathway activity, which promotes de novo purine biosynthesis and redox balance, and is required to maintain stemness during early fate determination after division. Our results demonstrate that fate decisions are susceptible to intrinsic metabolic bias imposed by selectively inherited mitochondria.
Topics: Adult Stem Cells; Animals; Cell Differentiation; Cell Line; Cell Lineage; Cell Proliferation; Cellular Senescence; DNA, Mitochondrial; Energy Metabolism; Female; Genes, Mitochondrial; Humans; Mammary Glands, Human; Metabolome; Mice, Inbred C57BL; Mice, Transgenic; Mitochondria; Phenotype; Proteome; Mice
PubMed: 35165416
DOI: 10.1038/s41556-021-00837-0