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Cellular and Molecular Life Sciences :... Oct 2018Mesenchymoangioblast (MB) is the earliest precursor for endothelial and mesenchymal cells originating from APLNRPDGFRαKDR mesoderm in human pluripotent stem cell... (Review)
Review
Mesenchymoangioblast (MB) is the earliest precursor for endothelial and mesenchymal cells originating from APLNRPDGFRαKDR mesoderm in human pluripotent stem cell cultures. MBs are identified based on their capacity to form FGF2-dependent compact spheroid colonies in a serum-free semisolid medium. MBs colonies are composed of PDGFRβCD271EMCNDLK1CD73 primitive mesenchymal cells which are generated through endothelial/angioblastic intermediates (cores) formed during first 3-4 days of clonogenic cultures. MB-derived primitive mesenchymal cells have potential to differentiate into mesenchymal stromal/stem cells (MSCs), pericytes, and smooth muscle cells. In this review, we summarize the specification and developmental potential of MBs, emphasize features that distinguish MBs from other mesenchymal progenitors described in the literature and discuss the value of these findings for identifying molecular pathways leading to MSC and vasculogenic cell specification, and developing cellular therapies using MB-derived progeny.
Topics: Autoimmune Diseases; Cell Lineage; Embryonic Development; Endothelial Cells; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mesoderm; Pluripotent Stem Cells; Spheroids, Cellular
PubMed: 29992471
DOI: 10.1007/s00018-018-2871-3 -
RNA Biology Dec 2017Epithelial-mesenchymal interactions are required to coordinate cell proliferation, patterning, and functional differentiation of multiple cell types in a developing... (Review)
Review
Epithelial-mesenchymal interactions are required to coordinate cell proliferation, patterning, and functional differentiation of multiple cell types in a developing organ. This exquisite coordination is dependent on various secreted molecules that provide developmental signals to mediate these tissue interactions. Recently, it was reported that mature mesenchymal-derived microRNAs (miRNAs) in the fetal mouse salivary gland are loaded into exosomes, and transported to the epithelium where they influence progenitor cell proliferation. The exosomal miRNAs regulated epithelial expression of genes involved in DNA methylation in progenitor cells to influence morphogenesis. Thus, exosomal miRNAs are mobile genetic signals that cross tissue boundaries within an organ. These findings raise many questions about how miRNA signals are initiated to coordinate organogenesis and whether they are master regulators of epithelial-mesenchymal interactions. The development of therapeutic applications using exosomal miRNAs for the regeneration of damaged adult organs is a promising area of research.
Topics: Animals; Biological Transport; Epithelial Cells; Epithelium; Exosomes; Extracellular Vesicles; Humans; Mesoderm; MicroRNAs; Molecular Diagnostic Techniques; Organogenesis; Salivary Glands; Signal Transduction
PubMed: 28816640
DOI: 10.1080/15476286.2017.1361098 -
Birth Defects Research. Part A,... Jan 2012Bronchopulmonary dysplasia (BPD) is a chronic lung disease in infants born extremely preterm, typically before 28 weeks' gestation, characterized by a prolonged need for... (Review)
Review
Bronchopulmonary dysplasia (BPD) is a chronic lung disease in infants born extremely preterm, typically before 28 weeks' gestation, characterized by a prolonged need for supplemental oxygen or positive pressure ventilation beyond 36 weeks postmenstrual age. The limited number of autopsy samples available from infants with BPD in the postsurfactant era has revealed a reduced capacity for gas exchange resulting from simplification of the distal lung structure with fewer, larger alveoli because of a failure of normal lung alveolar septation and pulmonary microvascular development. The mechanisms responsible for alveolar simplification in BPD have not been fully elucidated, but mounting evidence suggests that aberrations in the cross-talk between growth factors of the lung mesenchyme and distal airspace epithelium have a key role. Animal models that recapitulate the human condition have expanded our knowledge of the pathology of BPD and have identified candidate matrix components and growth factors in the developing lung that are disrupted by conditions that predispose infants to BPD and interfere with normal vascular and alveolar morphogenesis. This review focuses on the deviations from normal lung development that define the pathophysiology of BPD and summarizes the various candidate mesenchyme-associated proteins and growth factors that have been identified as being disrupted in animal models of BPD. Finally, future areas of research to identify novel targets affected in arrested lung development and recovery are discussed.
Topics: Animals; Bronchopulmonary Dysplasia; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Intercellular Signaling Peptides and Proteins; Lung; Mesoderm; Mice; Proteins; Signal Transduction
PubMed: 22125178
DOI: 10.1002/bdra.22869 -
The Anatomical Record Jun 1996Morphogenesis and cell differentiation during the development of all organs, including the tooth, are regulated by interactions between cells and tissues. The developing... (Review)
Review
BACKGROUND
Morphogenesis and cell differentiation during the development of all organs, including the tooth, are regulated by interactions between cells and tissues. The developing tooth is one of the organs in which the molecular mechanisms of such interactions are starting to be elucidated.
RESULTS
Homotypic cell interactions take place between cells of the same developmental history, and they are a central mechanism in the formation of mesenchymal cell condensates during the bud stage of tooth development. Syndecan-1, a cell surface heparan sulfate proteoglycan, is transiently expressed in the dental mesenchyme and may regulate dental mesenchymal cell condensation. It binds tenascin, a matrix glycoprotein abundant in dental mesenchyme, suggesting involvement of cell-matrix interactions. Syndecan also binds growth factors, and its association with cell proliferation in the dental mesenchyme suggests roles in the regulation of cell number in the condensing cells. Inductive interactions between the epithelial and mesenchymal tissues regulate tooth development at all stages. In the early dental mesenchyme, the expression of several molecules, including syndecan and tenascin, are regulated by the epithelium. There is evidence that growth factors act as diffusible signals mediating these interactions. BMP-2 and BMP-4 (bone morphogenetic proteins), which belong to the TGF beta superfamily, are expressed in the early dental epithelium, and their effects on the dental mesenchyme mimic those of the epithelium. In particular, BMPs induce the expression of the homeobox-containing transcription factors Msx-1 and Msx-2 in the dental mesenchyme.
CONCLUSIONS
Based on current knowledge about the molecular changes accompanying tooth development and the results of experimental studies, we present a model for molecular regulation of early tooth development.
Topics: Animals; Cell Differentiation; Epithelium; Extracellular Matrix Proteins; Gene Expression Regulation, Developmental; Growth Substances; Mesoderm; Mice; Odontogenesis; Signal Transduction; Tooth; Up-Regulation
PubMed: 8769660
DOI: 10.1002/(SICI)1097-0185(199606)245:2<151::AID-AR4>3.0.CO;2-# -
Cell Jan 2017The immune system safeguards organ integrity by employing a balancing act of inflammatory and immunosuppressive mechanisms designed to neutralize foreign invaders and... (Review)
Review
The immune system safeguards organ integrity by employing a balancing act of inflammatory and immunosuppressive mechanisms designed to neutralize foreign invaders and resolve injury. Maintaining or restoring a state of immune homeostasis is particularly challenging at barrier sites where constant exposure to immunogenic environmental agents may induce destructive inflammation. Recent studies underscore the role of epithelial and mesenchymal barrier cells in regulating immune cell function and local homeostatic and inflammatory responses. Here, we highlight immunoregulatory circuits engaging epithelial and mesenchymal cells in the intestine, airways, and skin and discuss how immune communications with hematopoietic cells and the microbiota orchestrate local immune homeostasis and inflammation.
Topics: Animals; Epithelial Cells; Epithelium; Homeostasis; Humans; Infections; Inflammation; Intestines; Mesoderm; Respiratory System
PubMed: 28129537
DOI: 10.1016/j.cell.2016.11.040 -
Three-axis classification of mouse lung mesenchymal cells reveals two populations of myofibroblasts.Development (Cambridge, England) Mar 2022The mesenchyme consists of heterogeneous cell populations that support neighboring structures and are integral to intercellular signaling, but are poorly defined...
The mesenchyme consists of heterogeneous cell populations that support neighboring structures and are integral to intercellular signaling, but are poorly defined morphologically and molecularly. Leveraging single-cell RNA-sequencing, 3D imaging and lineage tracing, we classify the mouse lung mesenchyme into three proximal-distal axes that are associated with the endothelium, epithelium and interstitium, respectively. From proximal to distal: the vascular axis includes vascular smooth muscle cells and pericytes that transition as arterioles and venules ramify into capillaries; the epithelial axis includes airway smooth muscle cells and two populations of myofibroblasts - ductal myofibroblasts, surrounding alveolar ducts and marked by CDH4, HHIP and LGR6, which persist post-alveologenesis, and alveolar myofibroblasts, surrounding alveoli and marked by high expression of PDGFRA, which undergo developmental apoptosis; and the interstitial axis, residing between the epithelial and vascular trees and sharing the marker MEOX2, includes fibroblasts in the bronchovascular bundle and the alveolar interstitium, which are marked by IL33/DNER/PI16 and Wnt2, respectively. Single-cell imaging reveals a distinct morphology of mesenchymal cell populations. This classification provides a conceptual and experimental framework applicable to other organs.
Topics: Animals; Lung; Mesenchymal Stem Cells; Mesoderm; Mice; Myofibroblasts; Pulmonary Alveoli
PubMed: 35302583
DOI: 10.1242/dev.200081 -
The Journal of Investigative... Jun 2003Epithelial-mesenchymal interactions play pivotal roles in the morphogenesis of many organs and various types of appendages. During hair follicle development, extensive... (Review)
Review
Epithelial-mesenchymal interactions play pivotal roles in the morphogenesis of many organs and various types of appendages. During hair follicle development, extensive interactions between two embryologically different hair follicle compartments (epidermal keratinocytes and dermal papilla fibroblasts) lead to the formation of the hair shaft-producing mini-organ that shows cyclic activity during postnatal life with periods of active growth, involution and resting. During the hair cycle, the epithelium and the mesenchyme are regulated by a distinct set of molecular signals that are unique for every distinct phase of the hair cycle. In telogen hair follicles, epithelial-mesenchymal interactions are characterized by a predominance of inhibitory signals that retain the hair follicle in a quiescent state. During anagen, a large variety of growth stimulatory pathways are activated in the epithelium and in the mesenchyme, the coordination of which are essential for proper hair fiber formation. During catagen, the termination of anagen-specific signaling interactions between the epithelium and the mesenchyme leads to apoptosis in the hair follicle epithelium, while activation of selected signaling pathways promotes the transition of the dermal papilla into a quiescent state. The signaling exchange between the follicular epithelium and the mesenchyme is modulated by proteoglycans, such as versican, which may significantly enhance or reduce the biological activities of secreted growth stimulators. However, additional research will be required to bridge the gap between our current understanding of mechanisms underlying epithelial-mesenchymal interactions in hair follicles and the potential clinical application of growth modulators involved in those interactions. Further progress in this area of research will hopefully lead to the development of new drugs for the treatment of hair growth disorders.
Topics: Animals; Embryo, Mammalian; Epithelium; Hair Follicle; Humans; Mesoderm; Proteoglycans; Signal Transduction
PubMed: 12894994
DOI: 10.1046/j.1523-1747.2003.12171.x -
The International Journal of... Mar 1989A chain of reciprocal interactions between the epithelial and mesenchymal tissues regulates both morphogenesis and cell differentiation in the developing tooth. The very... (Review)
Review
A chain of reciprocal interactions between the epithelial and mesenchymal tissues regulates both morphogenesis and cell differentiation in the developing tooth. The very early interactions lead to budding of the oral epithelium and to the characteristic condensation of the neural crest-derived mesenchymal cells around the epithelial bud. During the bell stage of morphogenesis, the mesenchymal cells which are in contact with the dental epithelium differentiate into odontoblasts. In this reveiw article we summarize the results of our descriptive and experimental studies, which indicate that differentiation of the dental mesenchymal cells into odontoblasts, as well the condensation of dental mesenchymal cells at the bud stage, are regulated by interactions between the cell surface and the extracellular matrix. Transfilter studies where the dental epithelium and mesenchyme were cultured on opposite sides of Nuclepore filters, led to the hypothesis that the differentiation of dental mesenchymal cells into odontoblasts is triggered by interactions between the cell surface and the epithelial basement membrane matrix. Immunohistochemical localization of various matrix molecules showed that the matrix glycoproteins fibronectin and tenascin are accumulated in the dental basement membrane at the time of odontoblast differentiation. Fibronectin and tenascin are known to interact with each other, with other matrix molecules as well as with the cell surface, and also to influence cell shape. We suggest that fibronectin and tenascin are involved in the cell-matrix interaction which leads to the polarization and differentiation of odontoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Epithelium; Extracellular Matrix; Glycoproteins; Mesoderm; Morphogenesis; Odontogenesis; Tooth; Tooth Germ
PubMed: 2485706
DOI: No ID Found -
Methods in Molecular Biology (Clifton,... 2021The epithelial-mesenchymal transition (EMT) is a key process required for building the early body plan of metazoa. It involves coordinated and precisely timed changes in...
The epithelial-mesenchymal transition (EMT) is a key process required for building the early body plan of metazoa. It involves coordinated and precisely timed changes in multiple cell processes such as de-adhesion, motility, invasion, and cell polarity. While much has been learned about how embryos deploy epithelial-mesenchymal transitions since Betty Hay named the process decades ago, a number of things are still not well understood. Here I will discuss some of the big questions that remain, including how is all of this controlled, how does each of the cell biological events work, and how are they so nicely coordinated with one another?
Topics: Animals; Cell Adhesion; Cell Movement; Cell Polarity; Embryo, Nonmammalian; Epithelial-Mesenchymal Transition; Epithelium; Gastrulation; Humans; Mesoderm
PubMed: 32939708
DOI: 10.1007/978-1-0716-0779-4_2 -
Cell Proliferation Jun 2004The vascular network is a series of linked conduits of blood vessels composed of the endothelium, a monolayer of cells that adorn the vessel lumen and surrounding... (Review)
Review
The vascular network is a series of linked conduits of blood vessels composed of the endothelium, a monolayer of cells that adorn the vessel lumen and surrounding layer(s) of mesenchymal cells (vascular smooth muscle, pericytes and fibroblasts). In addition to providing structural support, the mesenchymal cells are essential for vessel contractility. The extracellular matrix is a major constituent of blood vessels and provides a framework in which these various cell types are attached and embedded. The composition and organization of vascular extracellular matrix is primarily controlled by the mesenchymal cells, and is also responsible for the mechanical properties of the vessel wall, forming complex networks of structural proteins which are highly regulated. The extracellular matrix also plays a central role in cellular adhesion, differentiation and proliferation. This review examines the cellular and extracellular matrix components of vessels, with specific emphasis on the regulation of collagen type I and implications in vascular disease.
Topics: Animals; Blood Vessels; Collagen Type I; Extracellular Matrix; Extracellular Matrix Proteins; Humans; Mesoderm; Myocytes, Smooth Muscle; Pericytes; Vascular Diseases
PubMed: 15144498
DOI: 10.1111/j.1365-2184.2004.00306.x