RNA-seq of human lens with cataracts, alopecia, & microdontia
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE124121 | GEO | 2021/12/12
REPOSITORIES: GEO
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Project description:Congenital cataract is one of the leading causes of blindness in children worldwide. About one third of congenital cataracts are caused by genetic defects. Previous studies have identified LSS as a causal gene for congenital cataracts. However, its roles in lens development remains largely unknown. Here, we performed RNA-seq on the lens of WT and Lss mutant (heterozygous and homozygous )at E14.5, identified that cholesterol synthesis signaling pathways were significantly downregulated. Overall, our study points out that LSS functions as a critical determinant of lens development, which will contribute to better understand LSS defects in cataractogenesis and develop therapies for cataract.
2021-12-23 | GSE185143 | GEO
Project description:Analysis of Tdrd7 deficiency in mouse lens epithelial-derived cell line at gene expression level. The hypothesis tested was that Tdrd7 is involved in post-transcriptional control of gene expression in the lens. Results provide evidence for differential regulation of genes involved in lens homeostasis and cataract formation in the absence of Tdrd7. In eukaryotic cells, cytoplasmic RNA granules (RGs) function in the post-transcriptional control of gene expression. However, the involvement of RGs and their component proteins in vertebrate organogenesis is unknown. We report two independent cases of pediatric cataract with loss-of-function mutations in TDRD7, which encodes a Tudor domain RNA binding protein. TDRD7 deficiency in chick lens produces cataracts, and Tdrd7 null mouse mutants develop cataracts, as well as features of glaucoma and male sterility due to azoospermia. In lens fiber cells, TDRD7 is necessary for the RG-mediated post-transcriptional control of critical lens mRNAs, while in the testis it functions as a component of a specialized RG, the chromatoid body. These findings define a new role for RGs in vertebrate organogenesis, and a novel mechanism for cataractogenesis. Total RNA obtained from P30 Lens from Tdrd7 null mice compared to that of Tdrd7 heterozygous mice.
2012-02-21 | E-GEOD-25776 | biostudies-arrayexpress
Project description:Analysis of Tdrd7 deficiency in mouse lens epithelial-derived cell line at gene expression level. The hypothesis tested was that Tdrd7 is involved in post-transcriptional control of gene expression in the lens. Results provide evidence for differential regulation of genes involved in lens homeostasis and cataract formation in the absence of Tdrd7. In eukaryotic cells, cytoplasmic RNA granules (RGs) function in the post-transcriptional control of gene expression. However, the involvement of RGs and their component proteins in vertebrate organogenesis is unknown. We report two independent cases of pediatric cataract with loss-of-function mutations in TDRD7, which encodes a Tudor domain RNA binding protein. TDRD7 deficiency in chick lens produces cataracts, and Tdrd7 null mouse mutants develop cataracts, as well as features of glaucoma and male sterility due to azoospermia. In lens fiber cells, TDRD7 is necessary for the RG-mediated post-transcriptional control of critical lens mRNAs, while in the testis it functions as a component of a specialized RG, the chromatoid body. These findings define a new role for RGs in vertebrate organogenesis, and a novel mechanism for cataractogenesis. Total RNA obtained from P4 Lens from Tdrd7 null mice compared to that of Tdrd7 heterozygous mice.
2012-02-21 | E-GEOD-25775 | biostudies-arrayexpress
Project description:Analysis of Tdrd7 deficiency in mouse lens epithelial-derived cell line at gene expression level. The hypothesis tested was that Tdrd7 is involved in post-transcriptional control of gene expression in the lens. Results provide evidence for differential regulation of genes involved in lens homeostasis and cataract formation in the absence of Tdrd7. In eukaryotic cells, cytoplasmic RNA granules (RGs) function in the post-transcriptional control of gene expression. However, the involvement of RGs and their component proteins in vertebrate organogenesis is unknown. We report two independent cases of pediatric cataract with loss-of-function mutations in TDRD7, which encodes a Tudor domain RNA binding protein. TDRD7 deficiency in chick lens produces cataracts, and Tdrd7 null mouse mutants develop cataracts, as well as features of glaucoma and male sterility due to azoospermia. In lens fiber cells, TDRD7 is necessary for the RG-mediated post-transcriptional control of critical lens mRNAs, while in the testis it functions as a component of a specialized RG, the chromatoid body. These findings define a new role for RGs in vertebrate organogenesis, and a novel mechanism for cataractogenesis. Total RNA obtained from Tdrd7 knockdown cells compared to lentiviral GFP control in 21EM15 lens epithelial-derived cell line
2012-02-21 | E-GEOD-25774 | biostudies-arrayexpress
Project description:Analysis of Tdrd7 deficiency in mouse lens epithelial-derived cell line at gene expression level. The hypothesis tested was that Tdrd7 is involved in post-transcriptional control of gene expression in the lens. Results provide evidence for differential regulation of genes involved in lens homeostasis and cataract formation in the absence of Tdrd7. In eukaryotic cells, cytoplasmic RNA granules (RGs) function in the post-transcriptional control of gene expression. However, the involvement of RGs and their component proteins in vertebrate organogenesis is unknown. We report two independent cases of pediatric cataract with loss-of-function mutations in TDRD7, which encodes a Tudor domain RNA binding protein. TDRD7 deficiency in chick lens produces cataracts, and Tdrd7 null mouse mutants develop cataracts, as well as features of glaucoma and male sterility due to azoospermia. In lens fiber cells, TDRD7 is necessary for the RG-mediated post-transcriptional control of critical lens mRNAs, while in the testis it functions as a component of a specialized RG, the chromatoid body. These findings define a new role for RGs in vertebrate organogenesis, and a novel mechanism for cataractogenesis.
2012-02-21 | GSE25776 | GEO
Project description:Analysis of Tdrd7 deficiency in mouse lens epithelial-derived cell line at gene expression level. The hypothesis tested was that Tdrd7 is involved in post-transcriptional control of gene expression in the lens. Results provide evidence for differential regulation of genes involved in lens homeostasis and cataract formation in the absence of Tdrd7. In eukaryotic cells, cytoplasmic RNA granules (RGs) function in the post-transcriptional control of gene expression. However, the involvement of RGs and their component proteins in vertebrate organogenesis is unknown. We report two independent cases of pediatric cataract with loss-of-function mutations in TDRD7, which encodes a Tudor domain RNA binding protein. TDRD7 deficiency in chick lens produces cataracts, and Tdrd7 null mouse mutants develop cataracts, as well as features of glaucoma and male sterility due to azoospermia. In lens fiber cells, TDRD7 is necessary for the RG-mediated post-transcriptional control of critical lens mRNAs, while in the testis it functions as a component of a specialized RG, the chromatoid body. These findings define a new role for RGs in vertebrate organogenesis, and a novel mechanism for cataractogenesis.
2012-02-21 | GSE25775 | GEO
Project description:Analysis of Tdrd7 deficiency in mouse lens epithelial-derived cell line at gene expression level. The hypothesis tested was that Tdrd7 is involved in post-transcriptional control of gene expression in the lens. Results provide evidence for differential regulation of genes involved in lens homeostasis and cataract formation in the absence of Tdrd7. In eukaryotic cells, cytoplasmic RNA granules (RGs) function in the post-transcriptional control of gene expression. However, the involvement of RGs and their component proteins in vertebrate organogenesis is unknown. We report two independent cases of pediatric cataract with loss-of-function mutations in TDRD7, which encodes a Tudor domain RNA binding protein. TDRD7 deficiency in chick lens produces cataracts, and Tdrd7 null mouse mutants develop cataracts, as well as features of glaucoma and male sterility due to azoospermia. In lens fiber cells, TDRD7 is necessary for the RG-mediated post-transcriptional control of critical lens mRNAs, while in the testis it functions as a component of a specialized RG, the chromatoid body. These findings define a new role for RGs in vertebrate organogenesis, and a novel mechanism for cataractogenesis.
2012-02-21 | GSE25774 | GEO
Project description:Previous studies have reported that a strong correlation between the estimated cumulative thermal exposure in the crystalline lens and the incidence of nuclear cataracts; however, the precise relationship between temperature and cataracts remains to be fully elucidated. In the present study, the shotgun liquid chromatography/mass spectroscopy-based global proteomic approach was applied to investigate cataract-inducing factors in lens cultured at normal (35.0˚C) and slightly warmer (37.5˚C) conditions. In the rat lens, 190 proteins (total) were identified. Of these, 48 proteins (25.3%) were found in lenses cultured at both 35.0˚C and 37.5˚C. Moreover, 85 proteins (44.7%) were unique to lenses cultured at 35.0˚C, while 57 proteins (30.0%) were unique to lenses cultured at 37.5˚C. Protein expression changes in rat lenses cultured at 37.5˚C were examined using a label-free semiquantitative approach that uses spectral counting and Gene Ontology analysis. Filensin and vimentin protein expression, key factors in maintaining lens structure, were decreased. These findings may serve as a valuable indicator for elucidating the relationship between temperature and the onset of nuclear cataracts.
2024-09-22 | PXD056067 | JPOST Repository
Project description:Disruption of the mouse gene encoding the gap junction subunit alpha3 connexin 46 (Cx46) results in the formation of lens cataracts. The timing of the onset of this lens opacity is affected by the genetic background, i.e. the mouse strain. To elucidate the mechanism by which cataracts form in the 129Sv/Jae strain earlier than in the C57BL/6J strain, global gene expression was quantitated in the lenses of these strains. Lens cDNAs were analyzed by hybridization to DNA microarrays and with real time-PCR. Theories are proposed based on the observed higher level of expression of the stress-response genes in the C57BL/6J strain and variations in the expression levels of genes involved in protein synthesis, metabolism, catabolism and cell proliferation. How these variations in gene expression might affect the response of lens fiber cells to the increased calcium, caused by lack of alpha3Cx46, is considered. The possibility that the proteins coded by the strain-variable genes might influence the cataract-associated proteolysis of gamma-crystallin is also addressed. Keywords: Lens, cataract, microarray, connexin 46, gene knock out
2009-05-01 | GSE5645 | GEO
Project description:Mutations of the RNA-granule component TDRD7 (OMIM: 611258) cause pediatric cataract in humans. Here, we applied an integrated approach to elucidate the molecular pathology of cataract in Tdrd7 targeted-knockout (Tdrd7-/-) mice. Tdrd7-/- animals precipitously develop lens fiber cell abnormalities early in life, suggesting a global-level breakdown/mis-regulation of key cellular processes. High-throughput RNA-sequencing followed by iSyTE-integrated bioinformatics-based analysis identified the molecular chaperone and cytoskeletal-modulator, HSPB1 (HSP27), among the high-priority down-regulated candidates in Tdrd7-/- lens. Moreover, a protein 2-D fluorescence difference gel electrophoresis-coupled mass spectrometry screen also identified HSPB1 to be reduced in Tdrd7-/- lens, offering independent support for focusing efforts on this factor to explain Tdrd7-/- cataract. Reduction of HSPB1 preceded lens morphological abnormalities, suggesting that cytoskeletal defects underlie the Tdrd7-/- cataract phenotype. In agreement, scanning electron microscopy revealed abnormal fiber cell membrane protrusions in Tdrd7-/- lenses. Significantly, abnormal F-actin staining was detected specifically in Tdrd7-/- fiber cells that exhibit nuclear degradation, thereby revealing that there are distinct mechanisms based on pre- or post-nuclear degradation differentiation stage for F-actin cytoskeletal maintenance in fiber cells. Further, RNA-immunoprecipitation identified Hspb1 mRNA in wild-type lens lysate TDRD7-pulldowns, and single-molecule RNA-imaging showed co-localization of TDRD7 protein with cytoplasmic Hspb1 mRNA in a specific pre-nuclear degradation area of differentiating fiber cells, indicating that TDRD7-ribonucleoprotein complexes are necessary for controlling optimal levels of key factors in lens development. Together, these data uncover a novel role for TDRD7 in regulating elevation of stress-responsive chaperones for cytoskeletal maintenance in post-nuclear degradation lens fiber cells, perturbation of which causes early-onset cataracts.
2020-09-01 | GSE134384 | GEO