Transfer of extracellular matrix components between germ layers in chimaeric chicken-quail blastoderms

Summary A chemical basis for the transmission of signals during gastrulation has been investigated by using chimaeric embryos resulting from the combination of ³H-glucosamine-labelled and unlabelled hypoblast with epiblast taken from chicken and quail embryos at stage 3 of Vakaet (1970). The ability to distinguish chicken from quail cells on the basis of their different nuclear distribution of heterochromatin after Feulgen staining made it possible to determine the origin of the cells in the chimaerae. Tritiated quail hypoblast (after incubation of the embryo in the presence of ³H-glucosamine) was transplanted onto unlabelled chicken blastoderm deprived of its hypoblast. After culture of the chimaera for 5 h, the autoradiographic pattern shows silver grains not only over the graft, but also at the ventral surface of the epiblast of the host. Transfer of label may occur to mesoblast cells, but not between chicken and quail hypoblast cells. Chase experiments exclude the possibility that unprocessed, tritiated glucosamine is transferred. Chemical fixation of the host before transplantation of a labelled quail hypoblast also allows visualization of a transfer of macromolecules from hypoblast to the basement membrane of the epiblast, suggesting that an intervention of the epiblast cells in this process is not necessary. The morphology of the chimaeric embryos, as studied by scanning electron microscopy, suggests a direct deposition of these macromolecules by filopodia of the dorsal surface of the hypoblast. The possibility of diffusion of free macromolecules has been considered and can reasonably be discarded on the basis of several observations. The reverse experiment, in which unlabelled quail hypoblast and possibly some mesoblast have been combined with a tritiated host deprived of its hypoblast, also shows the transfer of label from the host to the cellular surface of the graft. A two-way exchange of glucosamine-containing molecules thus occurs in the blastoderm. It is hypothesized that: (1) low molecular weight compounds, macromolecular material, and/or catabolic products, are exchanged between the different germ layers during gastrulation; (2) the components of the extracellular matrix turn over and are continuously changing; (3) this transfer is a possible mechanism of transmission for developmental or inductive signals during embryonic development. The present results also demonstrate the participation of underlying tissue in the biosynthesis of basement membrane components of an epithelium.     

Detection of mosaicism in lymphocytes of parents of free trisomy 21 offspring

Down syndrome (DS) resulting from free trisomy 21 (FT21) has been largely associated with advanced maternal age. However, approximately 60% of FT21 cases are born to young couples. Thus, the etiological factors responsible for these FT21 children must differ from those proposed for maternal age-related FT21. These factors have not been defined. In this study, we analyzed the chromosomes of peripheral blood lymphocytes from three groups of couples aged ≤35 years, to identify chromosomal trisomies: Group I included 5 couples with normal offspring; Group II included 22 couples with one FT21 child; and Group III consisted of 3 couples with recurrent FT21. A total of 13,809 metaphases were analyzed with G-banding and 60,205 metaphases were analyzed with FISH using a 13/21 centromeric probe. Aneuploidy was significantly more frequent in Groups II and III. The frequencies of hyperdiploid cells were 0.19, 0.49 and 0.96% in Groups I–III, respectively. FISH analysis showed that trisomy 21 cell percentages were 0.08, 0.21 and 0.76 for Groups I–III, respectively, and were very similar to those obtained with G-banding. Trisomy 21 mosaicism was found in 2/22 couples with one FT21 offspring, and in 2/3 couples with recurrent FT21. Our data suggest that mosaicism is an important cause of FT21 offspring in young couples, and that aneuploidy is more frequent among couples with FT21 offspring. This may be related with age and other undetermined intrinsic and extrinsic factors.     

Recovery of extracellular matrix components by enalapril maleate during the repair process of ultraviolet B-induced wrinkles in mouse skin

The renin–angiotensin system is known to be involved in skin remodeling and inflammation. Previously, we reported that ultraviolet B (UVB) irradiation enhanced angiotensin-converting enzyme (ACE) expression and angiotensin II levels in hairless mouse skin, and an ACE inhibitor, enalapril maleate (EM), accelerated repair of UVB-induced wrinkles. In this study, we analyzed gene expression profiles by DNA microarray and protein distribution patterns using an immunofluorescence method to clarify the process of EM-accelerated wrinkle repair in UVB-irradiated hairless mouse skin. In the microarray analysis, we detected EM-induced up-regulation of various extracellular matrix (ECM)-related genes in the UVB-irradiated skin. In the immunofluorescence, we confirmed that type I collagen α1 chain, fibrillin 1, elastin and dystroglycan 1 in the skin decreased after repeated UVB irradiation but staining for these proteins was improved by EM treatment. In addition, ADAMTS2 and MMP-14 also increased in the EM-treated skin. Although the relationship between these molecules and wrinkle formation is not clear yet, our present data suggest that the molecules are involved in the repair of UVB-induced wrinkles.     

Contribution of ultrasonographic examination to the prenatal detection of trisomy 21: experience from 19 European registers

The objective of this study was to evaluate the contribution of ultrasound scanning to the prenatal detection of trisomy 21 in a large unselected European population. Data from 19 congenital malformation registers in 11 European countries were included. The prenatal ultrasound screening programs in the countries ranged from no routine screening to three ultrasound investigations per patient. Routine serum screening was offered in four of the 11 countries and routine screening on the basis of maternal age amniocentesis in all. The results show that overall 53% of cases of trisomy 21 were detected prenatally with a range from 3% in Lithuania to 88% in Paris. Ninety-eight percent of women whose babies were diagnosed before 24 weeks gestation chose to terminate the pregnancy. Centres/countries that offer serum screening do not have a significantly higher detection rate of trisomy 21 when compared to those that offer maternal age amniocentesis and anomaly scanning only. Fifty percent of trisomy 21 cases were born to women aged 35 years or more. In conclusions, second trimester ultrasound plays an important role in the prenatal diagnosis of trisomy 21. Of those cases prenatally diagnosed, 64% of cases in women <35 years and 36% of those in women >or=35 years were detected because of an ultrasound finding. Ultrasound soft markers accounted for 84% of the scan diagnoses. There is evidence of increasing maternal age across Europe with 50% of cases of trisomy 21 born to women aged 35 years or more.     

Pectin from transgenic flax shives regulates extracellular matrix remodelling in human skin fibroblasts

Pectin, a polysaccharide polymer from the plant cell wall, is an underestimated natural resource with many potential applications in the food and medical industries. Here we present, for the first time, the chemical composition of pectin obtained from flax shives, a by-product of flax fibre processing. The shives from transgenic flax overexpressing β-glucanase were analysed, revealing that genetic modification caused an increase in content of lignin, hemicellulose and pectin, without changes to cellulose, rearrangement of the structure of pectin and cellulose, a decrease in the content of phenolic compounds associated with the cell wall, and an increase in antioxidant capacity of the pectin CDTA fraction. The influence of pectin extract on the extracellular matrix remodelling process was verified. In fibroblast skin cells with induced oxidative stress, addition of pectin caused a reversal of the decrease of mRNA collagen genes, an increase of matrix metalloproteinase, interleukin 6 and MCP-1 gene expression, and a reduction in levels of TIMP-1 and SOCS-1 mRNA. The obtained results, in particular strong antioxidant properties of flax shives pectin from the CDTA-soluble fraction and its significant influence on genes participating in extracellular matrix remodelling, suggest the possible application of flax shives pectin in the wound healing process.     

Distribution of extracellular matrix proteins in odontogenic tumours and developing teeth

The distribution of two cellular fibronectins (cFn), tenascin, laminin, as well as type VII collagen was studied in 14 benign odontogenic tumours of epithelial (ameloblastoma) and epithelial-ectomesenchymal (ameloblastic fibroma) origins, as well as in developing human teeth by immunocytochemical means using monoclonal antibodies (Mabs). An extradomain sequence-A-containing form of cFn (EDA-cFn) was seen in the extracellular matrix (ECM) of all tumours studied and in the mesenchyme of the developing tooth germs, indicating that cFn in these tissues are predominantly produced locally. A form of cFn containing an oncofetal domain (Onc-cFn), hitherto found only in carcinomas, was detected focally in the stroma of most ameloblastomas but was absent from ameloblastic fibromas and tooth germs. Tenascin was strongly expressed in the basement membrane (BM) zone of all odontogenic tumours and in that of the early tooth germs. Focal absence of laminin and type VII collagen from the BM of some ameloblastomas and the presence of Onc-cFn in the ECM of most ameloblastomas may correlate with their aggressive behaviour. The results also suggest that EDA-cFn and tenascin are involved in epithelial-mesenchymal interactions during tooth development and in odontogenic tumours.     

Expression of versican in relation to chondrogenesis-related extracellular matrix components in canine mammary tumors

Versican plays a role in tumor cell proliferation and adhesion and may also regulate cell phenotype. Furthermore, it is one of the pivotal proteoglycans in mesenchymal condensation during prechondrogenesis. We have previously demonstrated accumulation of versican protein in myoepithelial-like spindle cell proliferations and myxoid tissues of complex and mixed mammary tumors of dogs. The objective of this study was to investigate whether the high expression of versican relates to prechondrogenesis in these tissues. Therefore, we aimed to identify cartilage markers, such as collagen type II and aggrecan both at mRNA and protein level in relation to versican. The neopitope of chondoitin-6-sulphate (3B3) known to be generated in developing cartilage has been investigated by immunohistochemisty and a panel of antibodies were used to characterize the phenotype of cells that are involved in cartilage formation. In addition, co-localization of versican with hyaluronan and link protein was studied. RT-PCR revealed upregulation of genes of versican, collagen type II and aggrecan in neoplastic tissues, especially in complex and mixed tumors. Immunohistochemistry showed the expression of cartilage biomarkers not only in the cartilagenous tissues of mixed tumors, but also in myoepitheliomas and in the myoepithelial-like cell proliferations and myxoid areas of complex and mixed tumors. The results show the cartilagenous differentiation of complex tumors and myoepitheliomas and indicate that the myxoid tissues and myoepithelial-like cell proliferations are the precursor tissues of the ectopic cartilage in mixed tumors. Furthermore, we suggest that cartilage formation in canine mammary tumors is a result of (myo)epithelial to mesenchymal transition.     

Correlation of extracellular matrix components with the cytoarchitecture of mouse Peyer's patches

Summary The distribution patterns of extracellular matrix elements were determined to ascertain whether they play a role in the localization of lymphocytes in discrete T-cell, B-cell and dome antigen-processing domains within Peyer's patches. Antibodies against collagen types I, III and IV, laminin and fibronectin were applied to cryosections of mouse Peyer's patches and localized by direct or indirect immunoperoxidase methods. T-cell domains were identified with a monoclonal antibody against Thy-1.2. Labeled reticular fibers in distinctive patterns were more numerous in parafollicular and dome areas than within follicles. Germinal centers contained few such fibers. In parafollicular areas, fibers were oriented predominantly toward follicle domes; their distribution corresponded to T-cell zones and lymphocyte traffic areas, with their orientation being parallel to the migration pathways of lymphocytes from high endothelial venules to the antigen-processing domes. Subepithelial and subendothelial basal laminae were immunopositive for type-IV collagen, laminin and fibronectin. The dome subepithelial basal lamina had pore-like discontinuities through which lymphocytes migrated to and from the epithelium. The correspondence of the distribution patterns of extracellular matrix to specific functional domains of Peyer's patches suggests that this matrix provides a structural framework for lymphocyte migration and localization.     

A novel proline-rich glycoprotein associated with the extracellular matrix of vascular bundles of Brassica petioles

A panel of monoclonal antibodies (MAC204, MAC236, MAC265) which recognise extracellular matrix glycoproteins implicated in plant-microbe interactions has been used to study glycoprotein antigens in petioles of turnip (Brassica campestris L.). While MAC204 recognised two glycoproteins (gp120 and gp45) with apparent M_r 120 000 and 45 000 in petiole extracts made with 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) buffer containing sodium dodecyl sulfate, MAC236 recognised gp120 but not gp45, and MAC265 gave no or only weak reactivity. Tissue dissection studies established that gp120 was predominantly associated with the vascular bundle whereas gp45 was largely associated with the pith. This was consistent with results from tissue prints probed with MAC204 and MAC236 which also suggested a vascular localisation for gp120. Immunoelectronmicroscopy showed that MAC204 and MAC236 both labelled three-way junctions between cells of the phloem and sclerid fibres. Both gp120 and gp45 were shown to carry epitopes in common with known hy`droxyproline-rich glycoproteins. Unlike gp45, gp120 could be extracted from petioles with Tris buffer alone and then isolated from this extract by trichloroacetic acid treatment (which left gp120 soluble), followed by size-exclusion and ion-exchange chromatography. Amino acid analysis revealed gp120 to be a novel glycoprotein, particularly rich in proline, lysine, valine and threonine but relatively poor in hydroxyproline. The most abundant sugars were arabinose and galactose. The potential role of this very basic cell surface glycoprotein in plant defence against microbes is discussed. Received: 25 November 1996 / Accepted: 12 December 1996     

Development of the electromotor system of Torpedo marmorata: Distribution of extracellular matrix and cytoskeletal components during acetylcholine receptor focalization

Summary A combination of direct fluorescence and indirect immunofluorescence microscopy has been used to compare the distribution of the acetylcholine receptor with the distribution of major cytoskeletal and extracellular matrix components during electrocyte differentiation in the electric organs of Torpedo marmorata. Laminin, fibronectin and extracellular matrix proteoglycan are always more extensively distributed around the differentiating cell than the acetylcholine receptor-rich patch that forms on the ventral surface of the cell. The distribution of acetylcholinesterase within the ventral surface of the differentiating electrocyte closely resembles the distribution of the acetylcholine receptor. Areas of apparently high acetylcholine receptor density within the ventrally forming acetylcholine receptor-rich patch are always areas of apparently high extracellular matrix proteoglycan density but are not always areas of high laminin or fibronectin density. Desmin levels appear to increase at the onset of differentiation and desmin initially accumulates in the ventral pole of each myotube as it begins to form an electrocyte. During differentiation F-actin-positive filament bundles are observed that extend from the nuclei down to the ventrally forming acetylcholine receptorrich patch. Most filament bundles terminate in the acetylcholine receptor-rich region of the cell membrane. Electronmicroscopic autoradiography suggests that the filament bundles attach to the membrane at sites where small acetylcholine receptor clusters are found. The results of this study suggest that, out of the four extracellular matrix components studied, only the distribution of acetylcholinesterase (which may be both matrix- and membrane-bound at this stage) closely parallels that of the acetylcholine receptor, and that F-actin filament bundles terminate in a region of the cell that is becoming an area of high acetylcholine receptor density.Abbreviations ACHR nicotinic acetylcholine receptor - ACHE acetylcholinesterase - BSA bovine serum albumin - EMPG extracellular matrix proteoglycan fraction - FITC fluorescein isothiocyanate - FN fibronectin - LN laminin - TBS Tris-HCl-buffered saline - SDS PAGE sodium dodecyl sulphate polyacrylamide gel electrophoresis     

Gaseous nitric oxide exhibits minimal effect on skin fibroblast extracellular matrix gene expression and immune cell viability

NO (nitric oxide) molecule is produced by various mammalian cell types and plays a significant role in inflammation, infection and wound healing processes. Recently, gNO (gaseous nitric oxide) therapy has been utilized for its potential clinical application as an antimicrobial agent, with special focus on skin infection. In a previous study, we demonstrated that 200 ppm gNO, 8 h/day for three consecutive days significantly reduced the number of bacteria in dermal wounds without compromising the viability and function of skin cells. To increase the feasibility and ease of its clinical use, we propose that different doses of gNO (5 to 10 K ppm) for 8 h and as short as 10 min be used, respectively. To achieve this, we set up in vitro experiments and asked whether (i) different doses of gNO have any toxic effect on immune cells and (ii) gNO has any modulating effect on key ECM (extracellular matrix) components in fibroblasts. To further investigate the effect of gNO, expression of more than 100 key ECM genes have been examined using gene array in human fibroblasts. As immune cells play an important role in wound healing, the effect of gNO on proliferation and viability of human and mouse lymphocytes was also examined. The findings showed that, the 5, 25, 75 and 200 ppm of gNO for 8 h slightly increased the expression of Col 5A3 (collagen type V alpha 3), and gNO at 5 ppm decreased the expression of MMP-1 (matrix metalloproteinase 1), while exposure of fibroblast to 10 K ppm of gNO for 10 min does not show any significant changes in ECM genes. Exposure to gNO resulted in inhibition of lymphocyte proliferation without affecting the cell viability. Taken together, our findings show that skin could be treated with gNO without compromising the role of ECM and immune cells in low concentrations with long time exposure or high concentrations for a shorter exposure time.     

Organization of rat mesenteric artery after removal of cells or extracellular matrix components

Summary Rat mesenteric arteries, perfusion fixed in relaxed or contracted conditions, were digested with acid and elastase, bleach (sodium hypochlorite), or alkali to selectively remove collagen, elastin, or cells. Scanning electron microscopy was used to study the three-dimensional organization of the remaining cells or extracellular components. Smooth muscle cells of the tunica media were elongated and circumferentially oriented. Superior mesenteric artery cells had an irregular surface with numerous projections and some ends were forked. Small mesenteric artery cells were spindle shaped with longitudinal surface ridges, and showed extensive corrugations upon contraction. Elastin was present both as laminae and as an interconnected fibrous meshwork. Collagen was arranged in an irregular network of individual fibrils and small bundles of fibrils that formed nests around the cells in both arteries. This irregular arrangement persisted, with no apparent reordering or loss of order, upon contraction. The lack of an ordered arrangement or specialized organization at the cell ends suggests mechanical coupling of the cells to elastin or collagen throughout the length of the cell, allowing for force transmission in a number of directions. The tunica media is thus a composite material consisting of cells, elastin, and collagen. The isotropic network of fibers is well suited for transmitting the shearing forces placed on it by contraction of smooth muscle cells and by pressure-induced loading.     

Collagen XII and XIV, new partners of cartilage oligomeric matrix protein in the skin extracellular matrix suprastructure

The tensile and scaffolding properties of skin rely on the complex extracellular matrix (ECM) that surrounds cells, vasculature, nerves, and adnexus structures and supports the epidermis. In the skin, collagen I fibrils are the major structural component of the dermal ECM, decorated by proteoglycans and by fibril-associated collagens with interrupted triple helices such as collagens XII and XIV. Here we show that the cartilage oligomeric matrix protein (COMP), an abundant component of cartilage ECM, is expressed in healthy human skin. COMP expression is detected in the dermal compartment of skin and in cultured fibroblasts, whereas epidermis and HaCaT cells are negative. In addition to binding collagen I, COMP binds to collagens XII and XIV via their C-terminal collagenous domains. All three proteins codistribute in a characteristic narrow zone in the superficial papillary dermis of healthy human skin. Ultrastructural analysis by immunogold labeling confirmed colocalization and further revealed the presence of COMP along with collagens XII and XIV in anchoring plaques. On the basis of these observations, we postulate that COMP functions as an adapter protein in human skin, similar to its function in cartilage ECM, by organizing collagen I fibrils into a suprastructure, mainly in the vicinity of anchoring plaques that stabilize the cohesion between the upper dermis and the basement membrane zone.     

Simian crease incidence and the correlation with thenar and hypothenar pattern types in Swedish patients with trisomy 21 (Down's syndrome)

In the present study the frequency of the simian crease among 57 Down patients is compared to the corresponding figures of related and unrelated individuals. A study of the correlation with the dermatoglyphic patterns of the thenar and hypothenar areas is presented, the palm print classification being carried out according to a Swedish method.     

Induction of surface-associated proteins of Streptococcus uberis by cultivation with extracellular matrix components and bovine mammary epithelial cells

Surface-associated protein expression by Streptococcus uberis was influenced by the presence of collagen, laminin and bovine mammary epithelial cells in the culture medium. After electrophoresis and silver staining, four proteins stained more intensively in samples from S. uberis cultivated with epithelial cells and extracellular matrix components than in samples from S. uberis cultivated alone. Induction of these proteins was more obvious after multiple bacterial passages. The correlation between the phenotype of S. uberis and its potential virulence status as illustrated by an immunoblotting study with sera obtained from infected cows revealed that these proteins are probably expressed in vivo during infection.     

Distribution and composition of extracellular polymeric substances in membrane-aerated biofilm

Extracellular polymeric substances (EPS) are one of the main components of the biofilm and perform important functions in the biofilm system. In this study, two membrane-aerated biofilms (MABs) were developed for the thin and thick biofilms under different surface loading rates (SLRs). Supplies of oxygen and substrates in the MAB were from two opposite directions. This counter diffusion of nutrients resulted in a different growth environment, in contrast to conventional biofilms receiving both oxygen and substrates from the same side. The compositions, distributions and physicochemical properties (solubility and bindability) of EPS in the MABs of different thicknesses under different SLRs were studied. The effect of dissolved oxygen (DO) concentration within the MAB on EPS properties and distribution was investigated. Experimental results showed the different biofilm thicknesses produced substantially different profiles of EPS composition and distribution. Soluble proteins were more dominant than soluble polysaccharides in the inner aerobic layer of the biofilms; in contrast, bound proteins were greater than bound polysaccharides in the outer anoxic or anaerobic layer of the biofilms. The biofilm-EPS matrix consisted mainly of bound EPS. Bound EPS exhibited a hump-shaped profile with the highest content occurring in an intermediate region in the thin MAB and relatively more uniformly in the one half of the biofilm close to the membrane side and then declined towards the biofilm-liquid interface in the thick MAB. The profiles of soluble EPS presented a similar declining trend from the membrane towards the outer region in both thin and thick MABs. The study suggested that not only EPS composition but also EPS distribution and properties (solubility and bindability) played a crucial role in controlling the cohesiveness and maintaining the structural stability and stratification of the MABs.     

Significance of the peri-insular extracellular matrix for islet isolation from the pancreas of rat,dog, pig,and man

Summary The presence and distribution in the peri-insular region of extracellular matrix, and in particular basement membrane, was investigated in a comparative study comprising pancreata of rat, dog, pig, and man. Basement membrane markers, collagen type-IV and laminin, were determined immunohistochemically. Additional information pertaining to the structural relationships between endocrine and exocrine pancreas, in particular cell-to-cell and cell-to-matrix contacts, was obtained by electron microscopy. In pig, very little periinsular capsule is present, and the structural integration of the porcine islet in the exocrine pancreas almost exclusively depends on cell-to-cell adhesion. In the canine pancreas, the islets are almost completely encapsulated with very little direct exocrine-to-endocrine cell-to-cell contact. In rat and man, the situation is intermediate with a tendency towards predominance of cell-to-matrix adhesion. The intra-insular adhesion mechanisms depend largely on cell-to-cell adhesion in all four species. The ultrastructural results suggest that collagenase preparations employed in islet isolation procedures should be of high purity as to preserve the protease-sensitive intra-islet cell-to-cell adhesion. Under these conditions, however, the endocrine-to-exocrine cell-to-cell contacts will be conserved also, resulting in an exocrine-tissue contamination of the islets of Langerhans. Consequently, additional steps for the effective removal of exocrine tissue and the purification of islets are required.     

Neural differentiation from pluripotent stem cells:The role of natural and synthetic extracellular matrix

Neural cells differentiated from pluripotent stem cells(PSCs), including both embryonic stem cells and induced pluripotent stem cells, provide a powerful tool for drug screening, disease modeling and regenerative medicine. High-purity oligodendrocyte progenitor cells(OPCs) and neural progenitor cells(NPCs) have been derived from PSCs recently due to the advancements in understanding the developmental signaling pathways. Extracellular matrices(ECM) have been shown to play important roles in regulating the survival, proliferation, and differentiation of neural cells. To improve the function and maturation of the derived neural cells from PSCs, understanding the effects of ECM over the course of neural differentiation of PSCs is critical. During neural differentiation of PSCs, the cells are sensitive to the properties of natural or synthetic ECMs, including biochemical composition, biomechanical properties, and structural/topographical features. This review summarizes recent advances in neural differentiation of humanPSCs into OPCs and NPCs, focusing on the role of ECM in modulating the composition and function of the differentiated cells. Especially, the importance of using three-dimensional ECM scaffolds to simulate the in vivo microenvironment for neural differentiation of PSCs is highlighted. Future perspectives including the immediate applications of PSC-derived neural cells in drug screening and disease modeling are also discussed.     

Neural differentiation from pluripotent stem cells: The role of natural and synthetic extracellular matrix简

Neural cells differentiated from pluripotent stem cells (PSCs), including both embryonic stem cells and induced pluripotent stem cells, provide a powerful tool for drug screening, disease modeling and regenerative medicine. High-purity oligodendrocyte progenitor cells (OPCs) and neural progenitor cells (NPCs) have been derived from PSCs recently due to the advancements in understanding the developmental signaling pathways. Extracellular matrices (ECM) have been shown to play important roles in regulating the survival, proliferation, and differentiation of neural cells. To improve the function and maturation of the derived neural cells from PSCs, understanding the effects of ECM over the course of neural differentiation of PSCs is critical. During neural differentiation of PSCs, the cells are sensitive to the properties of natural or synthetic ECMs, including biochemical composition, biomechanical properties, and structural/topographical features. This review summarizes recent advances in neural differentiation of human PSCs into OPCs and NPCs, focusing on the role of ECM in modulating the composition and function of the differentiated cells. Especially, the importance of using three-dimensional ECM scaffolds to simulate the in vivo microenvironment for neural differentiation of PSCs is highlighted. Future perspectives including the immediate applications of PSC-derived neural cells in drug screening and disease modeling are also discussed.     

Extracellular matrix control of mammary gland morphogenesis and tumorigenesis: insights from imaging

The extracellular matrix (ECM), once thought to solely provide physical support to a tissue, is a key component of a cell’s microenvironment responsible for directing cell fate and maintaining tissue specificity. It stands to reason, then, that changes in the ECM itself or in how signals from the ECM are presented to or interpreted by cells can disrupt tissue organization; the latter is a necessary step for malignant progression. In this review, we elaborate on this concept using the mammary gland as an example. We describe how the ECM directs mammary gland formation and function, and discuss how a cell’s inability to interpret these signals—whether as a result of genetic insults or physicochemical alterations in the ECM—disorganizes the gland and promotes malignancy. By restoring context and forcing cells to properly interpret these native signals, aberrant behavior can be quelled and organization re-established. Traditional imaging approaches have been a key complement to the standard biochemical, molecular, and cell biology approaches used in these studies. Utilizing imaging modalities with enhanced spatial resolution in live tissues may uncover additional means by which the ECM regulates tissue structure, on different length scales, through its pericellular organization (short-scale) and by biasing morphogenic and morphostatic gradients (long-scale). Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.