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The Journal of Clinical Investigation Jul 2023Mesenchymal cells are uniquely located at the interface between the epithelial lining and the stroma, allowing them to act as a signaling hub among diverse cellular... (Review)
Review
Mesenchymal cells are uniquely located at the interface between the epithelial lining and the stroma, allowing them to act as a signaling hub among diverse cellular compartments of the lung. During embryonic and postnatal lung development, mesenchyme-derived signals instruct epithelial budding, branching morphogenesis, and subsequent structural and functional maturation. Later during adult life, the mesenchyme plays divergent roles wherein its balanced activation promotes epithelial repair after injury while its aberrant activation can lead to pathological remodeling and fibrosis that are associated with multiple chronic pulmonary diseases, including bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. In this Review, we discuss the involvement of the lung mesenchyme in various morphogenic, neomorphogenic, and dysmorphogenic aspects of lung biology and health, with special emphasis on lung fibroblast subsets and smooth muscle cells, intercellular communication, and intrinsic mesenchymal mechanisms that drive such physiological and pathophysiological events throughout development, homeostasis, injury repair, regeneration, and aging.
Topics: Infant, Newborn; Humans; Lung; Pulmonary Disease, Chronic Obstructive; Fibrosis; Regeneration; Mesoderm; Epithelial Cells
PubMed: 37463440
DOI: 10.1172/JCI170498 -
Matrix Biology : Journal of the... Jun 2003Extracellular matrix (ECM) keratan sulfate proteoglycans (KSPGs) are core proteins with sulfated polylactosamine side chains (KS). The KSPG core protein keratocan gene...
Extracellular matrix (ECM) keratan sulfate proteoglycans (KSPGs) are core proteins with sulfated polylactosamine side chains (KS). The KSPG core protein keratocan gene (Kera) is expressed almost exclusively in adult vertebrate cornea, but its embryonic expression is little known. Embryonic chick in situ hybridization reveals Kera mRNA expression in corneal endothelium from embryonic day (E) 4.5, Hamburger-Hamilton (HH) 25, in stromal keratocytes from E6.5, HH30, and in iris distal surface cells from E8, HH34. As highly sulfated, antibody I22-positive KS increases extracellularly from posterior to anterior across the stroma, nerves enter and populate only anterior stroma and epithelium. RT-PCR and in situ hybridization demonstrate that developmentally regulated Kera mRNA expression initiates in midbrain and dorsolateral mesenchyme at E1, HH7, then spreads caudally in hindbrain and cranial and trunk mesenchyme flanking the neural tube through E2, HH20. Cranial expression extends ventrally through the developing head, and concentrates in mesenchyme surrounding eye anterior regions and cranial ganglia, and in subepidermal pharyngeal arch mesenchyme by E3.5, HH22. Kera expression in the trunk at E3.5, HH22 and E4.5, HH25, is strong in dorsolateral subepidermal, sclerotomal and nephrogenic mesenchymes, but absent in neural tube, dorsal root ganglia, nerve outgrowths, notochord, heart and gut. Early limb buds express Kera mRNA throughout their mesenchyme, then in restricted proximal and distal mesenchymes. I22-positive KS appears only in notochord in E3.5, HH22 and E4.5, HH25, embryos. Results suggest the hypothesis that keratocan, or keratocan with minimally sulfated KS chains, may play a role in structuring ECM for early embryonic cell and neuronal migrations.
Topics: Amino Acid Sequence; Animals; Brain; Chick Embryo; Chickens; Cornea; Extremities; Eye; Gene Expression Regulation, Developmental; In Situ Hybridization; Mesoderm; Molecular Sequence Data; Proteoglycans; RNA, Messenger
PubMed: 12935817
DOI: 10.1016/s0945-053x(03)00039-8 -
Developmental Biology Jul 2017Skeletogenic mesenchyme cells in echinoids are suitable for studying developmental mechanisms, and have been used extensively. Most of these studies have been performed... (Comparative Study)
Comparative Study Review
Skeletogenic mesenchyme cells in echinoids are suitable for studying developmental mechanisms, and have been used extensively. Most of these studies have been performed on species in the order Camarodonta, which are modern echinoids (subclass Euechinoidea) and are considered "model" echinoid species. In contrast, species belonging to other orders are studied less frequently, especially investigations of their molecular developmental biology such as gene regulatory networks. Recent studies on mesenchyme development in non-camarodont species suggest that these species are potential sources of comparative information to elucidate the mechanisms underlying skeletogenic mesenchyme development. In this review, the importance of using comparative data to understand development and evolution is discussed.
Topics: Animals; Mesoderm; Sea Urchins
PubMed: 27856261
DOI: 10.1016/j.ydbio.2016.11.011 -
Current Opinion in Genetics &... Jun 2015Each of the steps of respiratory system development relies on intricate interactions and coordinated development of the lung epithelium and mesenchyme. In the past, more... (Review)
Review
Each of the steps of respiratory system development relies on intricate interactions and coordinated development of the lung epithelium and mesenchyme. In the past, more attention has been paid to the epithelium than the mesenchyme. The mesenchyme is a source of specification and morphogenetic signals as well as a host of surprisingly complex cell lineages that are crucial for normal lung development and function. This review highlights recent research focusing on the mesenchyme that has revealed genetic and epigenetic mechanisms of its development in the context of other cell layers during respiratory lineage specification, branching morphogenesis, epithelial differentiation, lineage distinction, vascular development, and alveolar maturation.
Topics: Animals; Cell Differentiation; Cell Lineage; Epigenesis, Genetic; Humans; Lung; Mesoderm; Mice; Models, Biological; Morphogenesis; Respiratory Mucosa
PubMed: 25796078
DOI: 10.1016/j.gde.2015.01.011 -
Development (Cambridge, England) Nov 2023Tissue interactions are essential for guiding organ development and regeneration. Hair follicle formation relies on inductive signalling between two tissues, the...
Tissue interactions are essential for guiding organ development and regeneration. Hair follicle formation relies on inductive signalling between two tissues, the embryonic surface epithelium and the adjacent mesenchyme. Although previous research has highlighted the hair-inducing potential of the mesenchymal component of the hair follicle - the dermal papilla and its precursor, the dermal condensate - the source and nature of the primary inductive signal before dermal condensate formation have remained elusive. Here, we performed epithelial-mesenchymal tissue recombination experiments using hair-forming back skin and glabrous plantar skin from mouse embryos to unveil that the back skin mesenchyme is inductive even before dermal condensate formation. Moreover, the naïve, unpatterned mesenchyme was sufficient to trigger hair follicle formation even in the oral epithelium. Building on previous knowledge, we explored the hair-inductive ability of the Wnt agonist R-spondin 1 and a Bmp receptor inhibitor in embryonic skin explants. Although R-spondin 1 instigated precocious placode-specific transcriptional responses, it was insufficient for hair follicle induction, either alone or in combination with Bmp receptor inhibition. Our findings pave the way for identifying the hair follicle-inducing cue.
Topics: Mice; Animals; Hair Follicle; Hair; Skin; Mesoderm; Bone Morphogenetic Protein Receptors
PubMed: 37982496
DOI: 10.1242/dev.202140 -
Advances in Experimental Medicine and... 2023The structure of the mammalian lung controls the flow of air through the airways and into the distal alveolar region where gas exchange occurs. Specialized cells in the...
The structure of the mammalian lung controls the flow of air through the airways and into the distal alveolar region where gas exchange occurs. Specialized cells in the lung mesenchyme produce the extracellular matrix (ECM) and growth factors required for lung structure. Historically, characterizing the mesenchymal cell subtypes was challenging due to their ambiguous morphology, overlapping expression of protein markers, and limited cell-surface molecules needed for isolation. The recent development of single-cell RNA sequencing (scRNA-seq) complemented with genetic mouse models demonstrated that the lung mesenchyme comprises transcriptionally and functionally heterogeneous cell-types. Bioengineering approaches that model tissue structure clarify the function and regulation of mesenchymal cell types. These experimental approaches demonstrate the unique abilities of fibroblasts in mechanosignaling, mechanical force generation, ECM production, and tissue regeneration. This chapter will review the cell biology of the lung mesenchyme and experimental approaches to study their function.
Topics: Mice; Animals; Lung; Extracellular Matrix; Fibroblasts; Intercellular Signaling Peptides and Proteins; Mesoderm; Mammals
PubMed: 37195530
DOI: 10.1007/978-3-031-26625-6_8 -
International Journal of Molecular... Mar 2023Pancreatic cancer is one of the most lethal malignant diseases due to its high invasiveness, early metastatic properties, rapid disease progression, and typically late... (Review)
Review
Pancreatic cancer is one of the most lethal malignant diseases due to its high invasiveness, early metastatic properties, rapid disease progression, and typically late diagnosis. Notably, the capacity for pancreatic cancer cells to undergo epithelial-mesenchymal transition (EMT) is key to their tumorigenic and metastatic potential, and is a feature that can explain the therapeutic resistance of such cancers to treatment. Epigenetic modifications are a central molecular feature of EMT, for which histone modifications are most prevalent. The modification of histones is a dynamic process typically carried out by pairs of reverse catalytic enzymes, and the functions of these enzymes are increasingly relevant to our improved understanding of cancer. In this review, we discuss the mechanisms through which histone-modifying enzymes regulate EMT in pancreatic cancer.
Topics: Humans; Histone Code; Epithelial-Mesenchymal Transition; Pancreatic Neoplasms; Histones; Epigenesis, Genetic; Mesoderm
PubMed: 36902253
DOI: 10.3390/ijms24054820 -
Current Topics in Microbiology and... 2000We have reviewed the evidence that thymic mesenchymal cells and their progeny thymic fibroblasts play an important role in early T-cell development. Although it is... (Review)
Review
We have reviewed the evidence that thymic mesenchymal cells and their progeny thymic fibroblasts play an important role in early T-cell development. Although it is possible that mesenchyme plays an inductive role in thymic epithelial morphogenesis, we have presented evidence to suggest that there is a direct effect of mesenchyme and fibroblasts on T-cell development. Moreover the association of these cell types with an ECM raises the possibility that the latter might be important in integrin and/or cytokine presentation especially during the CD4(-)8- phase of T-cell development.
Topics: Cell Communication; Fibroblasts; Mesoderm; T-Lymphocytes; Thymus Gland
PubMed: 11036768
DOI: 10.1007/978-3-642-57276-0_17 -
Cancer Metastasis Reviews Sep 2006Tissues and organs harbor a component of supportive mesenchymal stroma. The organ stroma is vital for normal functioning since it expresses factors instructing growth... (Review)
Review
Tissues and organs harbor a component of supportive mesenchymal stroma. The organ stroma is vital for normal functioning since it expresses factors instructing growth and differentiation along with molecules that restrain these processes. Similarly, the growth of tumors is strictly dependent on the tumor stroma. This review first discusses the possibility of developing tools to block the propagation of the tumor-associated stroma, that may halt tumor progression. It further describes how the tropism of mesenchymal stroma to tumor sites may be utilized to cause regression of the cancerous tissue. Mesenchyme can be genetically modified to overexpress specific regulatory molecules with known effects on specific tumors, such as interferon beta, studied in the context of melanoma and glioma and activin A, a transforming growth factor beta cytokine, examined in multiple myeloma. These studies point to the possibility that genetically modified mesenchymal cells may be used as a therapeutic modality for incurable human diseases. It is proposed that further development of methods of tumor stroma targeting, or alternatively the use of stromal mesenchyme as a cell or cell/gene therapy modalities, may yield novel clinical tools for the treatment of human cancers.
Topics: Animals; Cytokines; Embryo, Mammalian; Genetic Therapy; Humans; Mesoderm; Neoplasms; Pharmaceutical Vehicles
PubMed: 17001513
DOI: 10.1007/s10555-006-9012-4 -
Trends in Genetics : TIG Oct 2012From both the fundamental and clinical perspectives, there is growing interest in mesenchymal cells and the mechanisms that regulate the two-way switch between... (Review)
Review
From both the fundamental and clinical perspectives, there is growing interest in mesenchymal cells and the mechanisms that regulate the two-way switch between mesenchymal and epithelial states. Here, we review recent findings showing that the Wilms' tumor gene (Wt1) is a key regulator of mesenchyme maintenance and the mesenchyme to epithelial balance in the development of certain mesodermal organs. We summarize recent experiments demonstrating, unexpectedly, that Wt1 is also essential for the integrity or function of multiple adult tissues, mainly, we argue, through regulating mesenchymal cells. We also discuss growing evidence that implicates Wt1 in tissue repair and regeneration. Drawing on these findings, we highlight the similarities between Wt1-expressing cells in different tissues. We believe that future studies aimed at elucidating the mechanisms underlying the functions of Wt1 in adult cells will reveal key cell types, pathways, and molecules regulating adult tissue homeostasis and repair.
Topics: Animals; Gene Expression Regulation, Developmental; Gene Expression Regulation, Neoplastic; Homeostasis; Humans; Mesoderm; Neoplasms; WT1 Proteins
PubMed: 22658804
DOI: 10.1016/j.tig.2012.04.004