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Results for “Cell Differentiation/physiology”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2001

Proliferation, differentiation and apoptosis in connexin43-null osteoblasts

Osteoblasts are highly coupled by gap junctions formed primarily by connexin43 (Cx43). We have shown that interference with Cx43 expression or function disrupts transcriptional regulation of osteoblast genes, and that deletion of Cx43 in the mouse causes skeletal malformations, delayed mineralization, and osteoblast dysfunction. Here, we studied the mechanisms by which genetic deficiency of Cx43 alters osteoblast development. While cell proliferation rates were similar in osteoblastic cells derived from calvaria of Cx43-null and wild type mice, camptothecin-induced apoptosis was 3-fold higher in mutant compared to wild type osteoblasts. When grown in mineralizing medium, Cx43-null cells were able to produce mineralized matrix but it took one week longer to reach the same mineralization levels as in normal cells. Likewise, expression of alkaline phosphatase activity per cell--a marker of osteoblast differentiation--was maximal only 2 weeks later in Cx43-null relative to wild-type cells. These observations suggest that Cx43 is important for a normal and timely development of the osteoblastic phenotype. Delayed differentiation and increase programmed cell death may explain the skeletal phenotype of Cx43-null mice.

NASA Discipline Cell Biology↗
NASA NTRS2000

Shape-dependent control of cell growth, differentiation, and apoptosis: switching between attractors in cell regulatory networks

Development of characteristic tissue patterns requires that individual cells be switched locally between different phenotypes or "fates;" while one cell may proliferate, its neighbors may differentiate or die. Recent studies have revealed that local switching between these different gene programs is controlled through interplay between soluble growth factors, insoluble extracellular matrix molecules, and mechanical forces which produce cell shape distortion. Although the precise molecular basis remains unknown, shape-dependent control of cell growth and function appears to be mediated by tension-dependent changes in the actin cytoskeleton. However, the question remains: how can a generalized physical stimulus, such as cell distortion, activate the same set of genes and signaling proteins that are triggered by molecules which bind to specific cell surface receptors. In this article, we use computer simulations based on dynamic Boolean networks to show that the different cell fates that a particular cell can exhibit may represent a preprogrammed set of common end programs or "attractors" which self-organize within the cell's regulatory networks. In this type of dynamic network model of information processing, generalized stimuli (e.g., mechanical forces) and specific molecular cues elicit signals which follow different trajectories, but eventually converge onto one of a small set of common end programs (growth, quiescence, differentiation, apoptosis, etc.). In other words, if cells use this type of information processing system, then control of cell function would involve selection of preexisting (latent) behavioral modes of the cell, rather than instruction by specific binding molecules. Importantly, the results of the computer simulation closely mimic experimental data obtained with living endothelial cells. The major implication of this finding is that current methods used for analysis of cell function that rely on characterization of linear signaling pathways or clusters of genes with common activity profiles may overlook the most critical features of cellular information processing which normally determine how signal specificity is established and maintained in living cells. Copyright 2000 Academic Press.

Review↗
NASA NTRS1991

Lateral root initiation in Marsilea quadrifolia. I. Origin and histogensis of lateral roots

In Marsilea quadrifolia, lateral roots arise from modified single cells of the endodermis located opposite the protoxylem poles within the meristematic region of the parent root. The initial cell divides in four specific planes to establish a five-celled lateral root primordium, with a tetrahedral apical cell in the centre and the oldest merophytes and the root cap along the sides. The cells of the merophyte divide in a precise pattern to give rise to the cells of the cortex, endodermis, pericycle, and vascular tissues of the emerging lateral root. Although the construction of the parent root is more complicated than that of lateral roots, patterns of cell division and tissue formation are similar in both types of roots, with the various tissues being arranged in similar positions in relation to the central axis. Vascular connection between the lateral root primordium and the parent root is derived from the pericycle cells lying between the former and the protoxylem members of the latter. It is proposed that the central axis of the root is not only a geometric centre, but also a physiological centre which determines the fate of the different cell types.

Non-NASA Center↗
NASA NTRS1998

Fibronectin is a survival factor for differentiated osteoblasts

The skeletal extracellular matrix produced by osteoblasts contains the glycoprotein fibronectin, which regulates the adhesion, differentiation and function of various adherent cells. Interactions with fibronectin are required for osteoblast differentiation in vitro, since fibronectin antagonists added to cultures of immature fetal calvarial osteoblasts inhibit their progressive differentiation. To determine if fibronectin plays a unique role in fully differentiated osteoblasts, cultures that had already formed mineralized nodules in vitro were treated with fibronectin antagonists. Fibronectin antibodies caused >95% of the cells in the mature cultures to display characteristic features of apoptosis (nuclear condensation, apoptotic body formation, DNA laddering) within 24 hours. Cells appeared to acquire sensitivity to fibronectin antibody-induced apoptosis as a consequence of differentiation, since antibodies failed to kill immature cells and the first cells killed were those associated with mature nodules. Intact plasma fibronectin, as well as fragments corresponding to the amino-terminal, cell-binding, and carboxy-terminal domains of fibronectin, independently induced apoptosis of mature (day-13), but not immature (day-4), osteoblasts. Finally, transforming growth factor-beta1 partially protected cells from the apoptotic effects of fibronectin antagonists. Thus, in the course of maturation cultured osteoblasts switch from depending on fibronectin for differentiation to depending on fibronectin for survival. These data suggest that fibronectin, together with transforming growth factor-beta1, may affect bone formation, in part by regulating the survival of osteoblasts.

NASA Center ARC↗
NASA NTRS1995

Integrin-extracellular matrix interactions in connective tissue remodeling and osteoblast differentiation

The differentiaton of bone cells is a complex multistep process. Bone is somewhat unusual in that it is very actively and continually remodeled in the adult and that maintenance of its mass in the mature organism is exquisitely sensitive to mechanical as well as chemical signals. Bone is also unique because it consists of a very large amount of extracellular matrix (ECM) that is mineralized. The integrin family of ECM receptors has been shown to play an important role in tissue morphogenesis in several systems. Our studies on the regulation of matrix remodeling enzymes by integrins in rabbit synovial fibroblasts show that two b1 integrin fibronectin (FN) receptor complexes (alpha 5 beta 1 and alpha 4 beta 1) cooperate in detecting subtle changes in the composition of the ECM. As a result of signal transduction by these integrins, the levels of mRNA and protein for several members of the metalloproteinase family are regulated in these cells. We have also used antibody and RGD peptide perturbation studies to determine the significance of cell/ECM interactions to normal osteogenesis. We found that interactions between the cell binding domain of FN and integrins are required for both normal morphogenesis and gene expression in cultured osteoblasts that differentiate to form bone-like tissue in culture. These data lead us to propose that beta 1 integrins play an important role in osteoblast differentiation as well as in bone remodeling.

NASA Discipline Number 26-10↗
NASA NTRS2001

Extracellular calcium sensing and extracellular calcium signaling

The cloning of a G protein-coupled extracellular Ca(2+) (Ca(o)(2+))-sensing receptor (CaR) has elucidated the molecular basis for many of the previously recognized effects of Ca(o)(2+) on tissues that maintain systemic Ca(o)(2+) homeostasis, especially parathyroid chief cells and several cells in the kidney. The availability of the cloned CaR enabled the development of DNA and antibody probes for identifying the CaR's mRNA and protein, respectively, within these and other tissues. It also permitted the identification of human diseases resulting from inactivating or activating mutations of the CaR gene and the subsequent generation of mice with targeted disruption of the CaR gene. The characteristic alterations in parathyroid and renal function in these patients and in the mice with "knockout" of the CaR gene have provided valuable information on the CaR's physiological roles in these tissues participating in mineral ion homeostasis. Nevertheless, relatively little is known about how the CaR regulates other tissues involved in systemic Ca(o)(2+) homeostasis, particularly bone and intestine. Moreover, there is evidence that additional Ca(o)(2+) sensors may exist in bone cells that mediate some or even all of the known effects of Ca(o)(2+) on these cells. Even more remains to be learned about the CaR's function in the rapidly growing list of cells that express it but are uninvolved in systemic Ca(o)(2+) metabolism. Available data suggest that the receptor serves numerous roles outside of systemic mineral ion homeostasis, ranging from the regulation of hormonal secretion and the activities of various ion channels to the longer term control of gene expression, programmed cell death (apoptosis), and cellular proliferation. In some cases, the CaR on these "nonhomeostatic" cells responds to local changes in Ca(o)(2+) taking place within compartments of the extracellular fluid (ECF) that communicate with the outside environment (e.g., the gastrointestinal tract). In others, localized changes in Ca(o)(2+) within the ECF can originate from several mechanisms, including fluxes of calcium ions into or out of cellular or extracellular stores or across epithelium that absorb or secrete Ca(2+). In any event, the CaR and other receptors/sensors for Ca(o)(2+) and probably for other extracellular ions represent versatile regulators of numerous cellular functions and may serve as important therapeutic targets.

Review↗
NASA NTRS1985

The involvement of glucose-6-phosphatase in mucilage secretion by root cap cells of Zea mays

In order to determine the involvement of glucose-6-phosphatase in mucilage secretion by root cap cells, we have cytochemically localized the enzyme in columella and peripheral cells of root caps of Zea mays. Glucose-6-phosphatase is associated with the plasmalemma and cell wall of columella cells. As columella cells differentiate into peripheral cells and begin to produce and secrete mucilage, glucose-6-phosphatase staining intensifies and becomes associated with the mucilage and, to a lesser extent, the cell wall. Cells being sloughed from the cap are characterized by glucose-6-phosphatase staining being associated with the vacuole and plasmalemma. These changes in enzyme localization during cellular differentiation in root caps suggest that glucose-6-phosphatase is involved in the production and/or secretion of mucilage by peripheral cells of Z. mays.

NASA Discipline Plant Biology↗
NASA NTRS1988

Kinetics of determination in the differentiation of isolated mesophyll cells of Zinnia elegans to tracheary elements

Mechanically isolated mesophyll cells of Zinnia elegans L. cv Envy differentiate to tracheary elements when cultured in inductive medium containing 0.5 micromolar alpha-naphthaleneacetic acid and 0.5 micromolar benzyladenine. The cells do not differentiate when cultured in medium in which the concentration of auxin and/or cytokinin has been reduced to 0.005 micromolar. Cells require an initial 24-hour exposure to inductive cytokinin and 56-hour exposure to inductive auxin for differentiation at 72 hours of culture. Freshly isolated Zinnia cells can be maintained in medium having low concentrations of both auxin and cytokinin for only 1 day without significant loss of potential to differentiate upon transfer to inductive medium. Initial culture for up to 2 days in medium having high auxin and low cytokinin, or low auxin and high cytokinin, allows full differentiation on the third day after transfer to inductive medium and potentiates the early differentiation of some cells.

Non-NASA Center↗
NASA NTRS1994

Class I and class II major histocompatibility molecules play a role in bone marrow-derived macrophage development

Class I and class II major histocompatibility complex (MHC) molecules play significant roles in T cell development and immune function. We show that MHCI- and MHCII-deficient mice have low numbers of macrophage precursors and circulating monocytes, as well as abnormal bone marrow cell colony-stimulating factor type 1 secretion and bone composition. We suggest that MHCI and MHCII molecules play a significant role in macrophage development.

Non-NASA Center↗
NASA NTRS1990

Gravity-induced changes in intracellular potentials in elongating cortical cells of mung bean roots

Gravity-induced changes in intracellular potentials in primary roots of 2-day-old mung bean (Vigna mungo L. cv. black matpe) seedlings were investigated using glass microelectrodes held by 3-dimensional hydraulic micro-drives. The electrodes were inserted into outer cortical cells within the elongation zone. Intracellular potentials, angle of root orientation with respect to gravity, and position within the root of the impaled cortical cell were measured simultaneously. Gravistimulation caused intracellular potential changes in cortical cells of the elongation zone. When the roots were oriented vertically, the intracellular potentials of the outer cortical cells (2 mm behind the root apex) were approximately - 115 mV. When the roots were placed horizontally cortical cells on the upper side hyperpolarized to - 154 mV within 30 s while cortical cells on the lower side depolarized to about - 62 mV. This electrical asymmetry did not occur in cells of the maturation zone. Because attempts to insert the electrode into cells of the root cap were unsuccessful, these cells were not measured. The hyperpolarization of cortical cells on the upper side was greatly reduced upon application of N,N'-dicyclohexylcarbodiimide (DCCD), an inhibitor of respiratory energy coupling. When stimulated roots were returned to the vertical, the degree of hyperpolarization of cortical cells on the previous upper side decreased within 30 s and approached that of cortical cells in non-stimulated roots. This cycle of hyperpolarization/loss of hyperpolarization was repeatable at least ten times by alternately turning the root from the vertical to the horizontal and back again. The very short (<30 s) lag period of these electrical changes indicates that they may result from stimulus-perception and transduction within the elongation zone rather than from transmission of a signal from the root cap.

NASA Discipline Plant Biology↗
NASA NTRS2003

Multilineage differentiation of rhesus monkey embryonic stem cells in three-dimensional culture systems

In the course of normal embryogenesis, embryonic stem (ES) cells differentiate along different lineages in the context of complex three-dimensional (3D) tissue structures. In order to study this phenomenon in vitro under controlled conditions, 3D culture systems are necessary. Here, we studied in vitro differentiation of rhesus monkey ES cells in 3D collagen matrixes (collagen gels and porous collagen sponges). Differentiation of ES cells in these 3D systems was different from that in monolayers. ES cells differentiated in collagen matrixes into neural, epithelial, and endothelial lineages. The abilities of ES cells to form various structures in two chemically similar but topologically different matrixes were different. In particular, in collagen gels ES cells formed gland-like circular structures, whereas in collagen sponges ES cells were scattered through the matrix or formed aggregates. Soluble factors produced by feeder cells or added to the culture medium facilitated ES cell differentiation into particular lineages. Coculture with fibroblasts in collagen gel facilitated ES cell differentiation into cells of a neural lineage expressing nestin, neural cell adhesion molecule, and class III beta-tubulin. In collagen sponges, keratinocytes facilitated ES cell differentiation into cells of an endothelial lineage expressing factor VIII. Exogenous granulocyte-macrophage colony-stimulating factor further enhanced endothelial differentiation. Thus, both soluble factors and the type of extracellular matrix seem to be critical in directing differentiation of ES cells and the formation of tissue-like structures. Three-dimensional culture systems are a valuable tool for studying the mechanisms of these phenomena.

Pluripotent Stem Cells/cytology/physiology↗
NASA NTRS2002

Apparent elastic modulus and hysteresis of skeletal muscle cells throughout differentiation

The effect of differentiation on the transverse mechanical properties of mammalian myocytes was determined by using atomic force microscopy. The apparent elastic modulus increased from 11.5 +/- 1.3 kPa for undifferentiated myoblasts to 45.3 +/- 4.0 kPa after 8 days of differentiation (P < 0.05). The relative contribution of viscosity, as determined from the normalized hysteresis area, ranged from 0.13 +/- 0.02 to 0.21 +/- 0.03 and did not change throughout differentiation. Myosin expression correlated with the apparent elastic modulus, but neither myosin nor beta-tubulin were associated with hysteresis. Microtubules did not affect mechanical properties because treatment with colchicine did not alter the apparent elastic modulus or hysteresis. Treatment with cytochalasin D or 2,3-butanedione 2-monoxime led to a significant reduction in the apparent elastic modulus but no change in hysteresis. In summary, skeletal muscle cells exhibited viscoelastic behavior that changed during differentiation, yielding an increase in the transverse elastic modulus. Major contributors to changes in the transverse elastic modulus during differentiation were actin and myosin.

NASA Discipline Musculoskeletal↗
NASA NTRS2003

An algorithm for neurite outgrowth reconstruction

We present a numerical method which provides the ability to analyze digitized microscope images of retinal explants and quantify neurite outgrowth. Few parameters are required as input and limited user interaction is necessary to process an entire experiment of images. This eliminates fatigue related errors and user-related bias common to manual analysis. The method does not rely on stained images and handles images of variable quality. The algorithm is used to determine time and dose dependent, in vitro, neurotoxic effects of 1 GeV per nucleon iron particles in retinal explants. No neurotoxic effects are detected until 72 h after exposure; at 72 h, significant reductions of neurite outgrowth occurred at doses higher than 10 cGy.

NASA Program Biomedical Research and Countermeasur↗
NASA NTRS2003

Tensegrity II. How structural networks influence cellular information processing networks

The major challenge in biology today is biocomplexity: the need to explain how cell and tissue behaviors emerge from collective interactions within complex molecular networks. Part I of this two-part article, described a mechanical model of cell structure based on tensegrity architecture that explains how the mechanical behavior of the cell emerges from physical interactions among the different molecular filament systems that form the cytoskeleton. Recent work shows that the cytoskeleton also orients much of the cell's metabolic and signal transduction machinery and that mechanical distortion of cells and the cytoskeleton through cell surface integrin receptors can profoundly affect cell behavior. In particular, gradual variations in this single physical control parameter (cell shape distortion) can switch cells between distinct gene programs (e.g. growth, differentiation and apoptosis), and this process can be viewed as a biological phase transition. Part II of this article covers how combined use of tensegrity and solid-state mechanochemistry by cells may mediate mechanotransduction and facilitate integration of chemical and physical signals that are responsible for control of cell behavior. In addition, it examines how cell structural networks affect gene and protein signaling networks to produce characteristic phenotypes and cell fate transitions during tissue development.

Review↗
NASA NTRS2002

Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology

Great advances have been made in the identification of the soluble angiogenic factors, insoluble extracellular matrix (ECM) molecules, and receptor signaling pathways that mediate control of angiogenesis--the growth of blood capillaries. This review focuses on work that explores how endothelial cells integrate these chemical signals with mechanical cues from their local tissue microenvironment so as to produce functional capillary networks that exhibit specialized form as well as function. These studies have revealed that ECM governs whether an endothelial cell will switch between growth, differentiation, motility, or apoptosis programs in response to a soluble stimulus based on its ability to mechanically resist cell tractional forces and thereby produce cell and cytoskeletal distortion. Transmembrane integrin receptors play a key role in this mechanochemical transduction process because they both organize a cytoskeletal signaling complex within the focal adhesion and preferentially focus mechanical forces on this site. Molecular filaments within the internal cytoskeleton--microfilaments, microtubules, and intermediate filaments--also contribute to the cell's structural and functional response to mechanical stress through their role as discrete support elements within a tensegrity-stabilized cytoskeletal array. Importantly, a similar form of mechanical control also has been shown to be involved in the regulation of contractility in vascular smooth muscle cells and cardiac myocytes. Thus, the mechanism by which cells perform mechanochemical transduction and the implications of these findings for morphogenetic control are discussed in the wider context of vascular development and cardiovascular physiology.

Non-NASA Center↗
NASA NTRS2001

Developmental regulation of N-methyl-D-aspartate- and kainate-type glutamate receptor expression in the rat spinal cord

Spinal motor neurons undergo experience-dependent development during a critical period in early postnatal life. It has been suggested that the repertoire of glutamate receptor subunits differs between young and mature motor neurons and contributes to this activity-dependent development. In the present study we examined the expression patterns of N-methyl-D-aspartate- and kainate-type glutamate receptor subunits during the postnatal maturation of the spinal cord. Young motor neurons express much higher levels of the N-methyl-D-aspartate receptor subunit NR1 than do adult motor neurons. Although there are eight potential splice variants of NR1, only a subgroup is expressed by motor neurons. With respect to NR2 receptor subunits, young motor neurons express NR2A and C, while adult motor neurons express only NR2A. Young motor neurons express kainate receptor subunits GluR5, 6 and KA2 but we are unable to detect these or any other kainate receptor subunits in the adult spinal cord. Other spinal cord regions display a distinct pattern of developmental regulation of N-methyl-D-aspartate and kainate receptor subunit expression in comparison to motor neurons. Our findings indicate a precise spatio-temporal regulation of individual subunit expression in the developing spinal cord. Specific combinations of subunits in developing neurons influence their excitable properties and could participate in the emergence of adult neuronal form and function.

NASA Discipline Cell Biology↗