Cell and Ultrastructure, A Functional Perspective

Cross, Patricia; Mercer, K. Lynne; Bozzola, John J.

doi:10.1017/s1551929500063501

Cited by 33 publications

(40 citation statements)

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“…Conducting airways were lined by non-ciliated columnar epithelial cells that contained numerous atypical electron dense organelles, consistent with the atypical mitochondria characteristic of Clara cells (Fig. 4B) (24). Type II cells were hypertrophic, containing increased numbers of lamellar bodies and lipid inclusions.…”

Section: Sp-c (ϫ/ϫ) 129/sv Congenicsupporting

confidence: 55%

Pneumonitis and Emphysema in sp-C Gene Targeted Mice

Glasser¹,

Detmer²,

Ikegami³

et al. 2003

Journal of Biological Chemistry

202

161

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Section: Sp-c (ϫ/ϫ) 129/sv Congenicsupporting

confidence: 55%

Pneumonitis and Emphysema in sp-C Gene Targeted Mice

Glasser¹,

Detmer²,

Ikegami³

et al. 2003

Journal of Biological Chemistry

202

161

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“…The different cell populations of the brain were distinguished according morphological criteria (48). Briefly, glial cells were distinguished from neurons by their smaller, more irregular shape and by the prominent differences in the nucleus (absence of nucleolus and with a condensed envelope).…”

Section: Methodsmentioning

confidence: 99%

Astrocyte dysfunction triggers neurodegeneration in a lysosomal storage disorder

Malta

Fryer

Settembre

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

105

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The role of astrocytes in neurodegenerative processes is increasingly appreciated. Here we investigated the contribution of astrocytes to neurodegeneration in multiple sulfatase deficiency (MSD), a severe lysosomal storage disorder caused by mutations in the sulfatase modifying factor 1 (SUMF1) gene. Using Cre/Lox mouse models, we found that astrocyte-specific deletion of Sumf1 in vivo induced severe lysosomal storage and autophagy dysfunction with consequential cytoplasmic accumulation of autophagic substrates. Lysosomal storage in astrocytes was sufficient to induce degeneration of cortical neurons in vivo. Furthermore, in an ex vivo coculture assay, we observed that Sumf1 −/− astrocytes failed to support the survival and function of wild-type cortical neurons, suggesting a non-cell autonomous mechanism for neurodegeneration. Compared with the astrocyte-specific deletion of Sumf1, the concomitant removal of Sumf1 in both neurons and glia in vivo induced a widespread neuronal loss and robust neuroinflammation. Finally, behavioral analysis of mice with astrocyte-specific deletion of Sumf1 compared with mice with Sumf1 deletion in both astrocytes and neurons allowed us to link a subset of neurological manifestations of MSD to astrocyte dysfunction. This study indicates that astrocytes are integral components of the neuropathology in MSD and that modulation of astrocyte function may impact disease course.ultiple sulfatase deficiency (MSD) is a lysosomal storage disorder (LSD) caused by mutations in the sulfatase modifying factor 1 (SUMF1) gene that results in aberrant posttranslation modification of sulfatases (1). Sulfatases are a family of enzymes required for the turnover and degradation of sulfated compounds. Eight known metabolic disorders are caused by the deficiency of individual sulfatase activities. Six are LSDs (five mucopolysaccharidoses and metachromatic leukodystrophy); the remaining two disorders are caused by deficiency of nonlysosomal sulfatases. The impaired activity of all sulfatases in MSD is responsible for a very severe phenotype that combines all the clinical symptoms found in each individual sulfatase deficiency (2). As in many other LSDs, progressive and severe neurodegeneration is a prominent feature and is the most difficult challenge for therapy (3). Previous studies identified impaired autophagy in neurons as a crucial component in the pathogenic mechanisms leading to neurodegeneration in MSD as well as in other LSDs (4,5). This lysosomal accumulation of undegraded substrates results in defective degradation of autophagosomes and causes a block of the autophagy pathway leading to an accumulation of ubiquitinated proteins, dysfunctional mitochondria, and neurodegeneration. To date, research has focused on neurons, but the contribution of nonneuronal cells to the neuropathology of MSD has remained largely unexplored.Astrocytes play crucial roles in adult CNS homeostasis (6), including synaptic glutamate uptake (7), maintenance of extracellular potassium (8), and nutrient support for neuro...

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“…Concentric-ring residual bodies (Fig. 9) may correspond to packed lipid membranes of incompletely digested aged organelles, 79 and their abundance also suggests elevated synthetic activity.…”

Section: Intracellular Structuresmentioning

confidence: 99%

Effect of Serum and Insulin Modulation on the Organization and Morphology of Matrix Synthesized by Bovine Corneal Stromal Cells

Bueno

Saeidi

Melotti

et al. 2009

Tissue Engineering Part A

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The in vitro production of highly organized collagen fibrils by corneal keratocytes in a three-dimensional scaffold-free culture system presents a unique opportunity for the direct observation of organized matrix formation. The objective of this investigation was to develop such a culture system in a glass substrate (for optical accessibility) and to directly examine the effect of reducing serum and=or increasing insulin on the stratification and secretion of aligned matrix by fourth-to fifth-passage bovine corneal stromal keratocytes. Medium concentrations of 0%, 1%, or 10% fetal bovine serum and 0% or 1% insulin-transferrin-selenium were investigated. Highresolution differential interference contrast microscopy, quick-freeze=deep-etch, and conventional transmission electron microscopy were used to monitor the evolution, morphology, and ultrastructure of the cell-matrix constructs. In a medium containing 1% each of serum and insulin-transferrin-selenium, stromal cells stratified and secreted abundant and locally aligned matrix, generating the thickest cell-matrix constructs (allowing handling with forceps). The results of this study have the potential to significantly advance the field of developmental functional engineering of load-bearing tissues by (i) elucidating cues that modulate in vitro cell secretion of organized matrix and (ii) establishing an optically accessible cell culture system for investigating the mechanism of cell secretion of aligned collagen fibrils.

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Cell and Ultrastructure, A Functional Perspective

Cited by 33 publications

References 0 publications

Pneumonitis and Emphysema in sp-C Gene Targeted Mice

Pneumonitis and Emphysema in sp-C Gene Targeted Mice

Astrocyte dysfunction triggers neurodegeneration in a lysosomal storage disorder

Effect of Serum and Insulin Modulation on the Organization and Morphology of Matrix Synthesized by Bovine Corneal Stromal Cells

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