Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Changes in nuclear lamin-B stability marks the onset of aging in Drosophila

ABSTRACT: In this study, we showed that reduced nuclear lamin-B marks the onset of physiological decline in young adult Drosophila and its ectopic expression in dopaminergic neurons is sufficient to improve their locomotor activity during aging. Furthermore, the decline in lamin-B protein appeared to be unrelated to its mRNA level. Instead, we found drastic changes to its protein solubility during aging. Given the importance of nuclear lamin-B in genome organization and the advancement of single-cell epigenome profiling technology, our findings provide the community the basis to further study how altered level of lamin-B protein may elicit changes in gene expression that can contribute to the onset of physiological decline in animals.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE155357 | GEO | 2021/11/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Age-dependent Lamin remodeling induces cardiac dysfunction via dysregulation of cardiac transcriptional programs [RNA-Seq]

Project description:As we age, structural changes contribute to progressive decline in organ function, which in the heart acts through poorly characterized mechanisms. Utilizing the rapidly aging fruit fly model with its significant homology to the human cardiac proteome, we found that cardiomyocytes exhibit progressive loss of Lamin C (mammalian Lamin A/C homologue) with age. Unlike other tissues and laminopathies, we observe decreasing nuclear size, while nuclear stiffness increases. Premature genetic reduction of Lamin C phenocopies aging’s effects on the nucleus, and subsequently decreases heart contractility and sarcomere organization. Surprisingly, Lamin C reduction downregulates myogenic transcription factors and cytoskeletal regulators, possibly via reduced chromatin accessibility. Subsequently, we find an adult-specific role for cardiac transcription factors and show that maintenance of Lamin C sustains their expression and prevents age-dependent cardiac decline. Our findings are conserved in aged non-human primates and mice, demonstrating age-dependent nuclear remodeling is a major mechanism contributing to cardiac dysfunction.

2022-11-01 | GSE185967 | GEO

Age-dependent Lamin remodeling induces cardiac dysfunction via dysregulation of cardiac transcriptional programs [ATAC-Seq]

2022-11-01 | GSE185923 | GEO

Changes in nuclear lamin-B stability marks the onset of aging in Drosophila

Project description:Changes in nuclear lamin-B stability marks the onset of aging in Drosophila

| PRJNA649516 | ENA

Declining Lamin B1 expression mediates age-dependent decreases of hippocampal stem cell activity

Project description:Neural stem cells (NSCs) generate neurons throughout life in the hippocampal dentate gyrus (DG). With advancing age levels of neurogenesis sharply drop, which has been associated with a decline in hippocampal memory function. However, cell-intrinsic mechanisms mediating age-related changes in NSC activity remain largely unknown. Here we show that the nuclear lamina protein Lamin B1 (LB1) is downregulated with age in mouse hippocampal NSCs. LB1 is cross-regulated with Sun-domain containing protein 1 (SUN1), previously implicated in Hutchinson-Gilford progeria syndrome (HGPS), a disease of premature aging. LB1 and SUN1 govern the strength of a diffusion barrier in the membrane of the endoplasmic reticulum (ER) that is associated with the segregation of aging factors during NSC divisions. Balancing the levels of LB1 and SUN1 in aged NSCs restores the ER-diffusion barrier. Virus-based restoration of LB1 expression in aged NSCs enhances stem cell activity in vitro and increases progenitor cell proliferation and neurogenesis in vivo. Thus, we here identify a novel mechanism associated with the age-related decline of neurogenesis in the mammalian hippocampus.

2020-12-24 | GSE163795 | GEO

Lamin B1 and LAP2β resist cytoskeletal force to maintain lamin A/C meshwork organization and preserve nuclear integrity

Project description:The nuclear lamins are extremely long-lived proteins in most cell types. As a consequence, lamin function cannot be effectively dissected with temporal precision using standard knock-down approaches. Here, we apply the auxin inducible degron (AID) system to rapidly deplete each lamin isoform within one cell cycle and reveal the immediate impacts of lamin loss on the nucleus . Surprisingly, neither acute lamin A/C (LA/C), lamin B1 (LB1), nor lamin B2 (LB2) depletion altered nuclear shape or induced nuclear blebbing, indicating that acute lamin loss is not sufficient to alter nuclear morphology. LB1 depletion is immediately followed by LA/C meshwork disorganization due to actin cytoskeletal forces on the lamina, yet neither LA/C nor LB1 depletion induced nuclear rupturing. We found that the abundant inner nuclear membrane protein LAP2β protects nuclear integrity in the absence of LB1, as depletion of both LB1 and LAP2β induced severe LA/C disorganization and frequent nuclear rupturing. Depolymerization of the actin cytoskeleton halts nuclear rupture in LAP2β- and LB1-depleted nuclei. We conclude that both LB1 and LAP2β resist cytoskeletal force to maintain regular lamin A/C meshwork organization and preserve nuclear integrity.

2025-02-17 | GSE289252 | GEO

Lamin A/C promotes DNA base excision repair (mouse arrays)

Project description:The A-type lamins (lamin A/C), encoded by the Lmna gene, are important structural components of the nuclear lamina. Lmna mutations lead to degenerative disorders, including the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). In addition, altered lamin A/C expression is found in various cancers. Reports indicate that lamin A/C plays a role in DNA double strand break repair, but a role in DNA base excision repair (BER) has not been described. We provide evidence for reduced BER efficiency in lamin A/C-depleted cells. The mechanism involves impairment of the APE1 and POLβ enzyme activities in BER. Also, Lmna null mouse fibroblasts displayed reduced expression of several core BER enzymes (PARP1, LIG3, and POLβ). Moreover, the robustness of APE1 and POLβ activities and the rate of BER were enhanced by lamin A/C-augmented poly(ADP-ribose) polymer formation (PARylation). Finally, we report that HGPS fibroblasts are defective in BER. Collectively, our results provide novel insights into the functional interplay between the nuclear lamina and cellular defenses against oxidative DNA damage, with implications for human cancer and aging.

2019-10-02 | GSE120389 | GEO

Lamin A/C promotes DNA base excision repair (human arrays)

2020-09-30 | GSE124465 | GEO

Structural basis for assembly of lamin at the molecular level

Project description:Nuclear structure and function are governed by lamins, which are intermediate filaments mostly consisting of alpha-helices. Different lamin assembly models have been proposed based on low resolution or fragmented structures. However, their assembly mechanisms at the molecular level are poorly understood. Here, we present a crystal structure of a long human lamin fragment at 3.2 Å resolution, which visualized the full-length features. The structure presented the anti-parallel arrangement of two coiled-coil dimers, which was important for the assembly process. We further discovered a new interaction between the lamin dimers by using chemical cross-linking and mass analysis. Based on these two interactions we proposed a molecular mechanism of lamin assembly, which agreed well with the recent model representing the native state, and could explain pathological mutations. Our findings provide the structural information to understand molecular mechanisms of assembly of intermediate filaments, and molecular insights into nuclear functions and aging process.

2019-08-26 | PXD013144 | Pride

Recapitulation of human premature aging by using iPSCs from Hutchinson-Gilford progeria syndrome

Project description:Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature aging disease1-5, characterized by premature atherosclerosis and degeneration of vascular smooth muscle cells (SMCs)6-8. HGPS is caused by a single-point mutation in the LMNA gene, resulting in the generation of progerin, a truncated mutant of lamin A. Accumulation of progerin leads to various aging-associated nuclear defects including disorganization of nuclear lamina and loss of heterochromatin9-12. Here, we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS-iPSCs show absence of progerin, and more importantly, lack the nuclear envelope and epigenetic alterations normally associated with premature aging. Upon differentiation of HGPS-iPSCs, progerin and its associated aging consequences are restored. In particular, directed differentiation of HGPS-iPSCs to SMCs leads to the appearance of premature senescent SMC phenotypes associated with vascular aging. Additionally, our studies identify DNA-dependent protein kinase catalytic subunit (DNAPKcs) as a component of the progerin-containing protein complex. The absence of nuclear DNAPKcs correlates with premature as well as physiological aging. Since progerin also accumulates during physiological aging6,12,13, our results provide an in vitro iPSC-based model with an acceleration progerin accumulation to study the pathogenesis of human premature and physiological vascular aging. Microarray gene expression profiling was done to: (1) Compare differences between WT fibroblasts and fibroblasts from patients suffering of the Hutchinson-Gilford progeria syndrome (2) Check that iPSC originating from WT and patients are in fact similar to ESC

2011-03-14 | E-GEOD-24487 | biostudies-arrayexpress

Microarray gene expression profiling of rat cerebellar Granule Cells (GCs) before and after Lamin A-knockdown

Project description:Nuclear lamins are nuclear type V intermediate filament proteins that form a meshwork structure underlying the inner nuclear membrane, the nuclear lamina. The nuclear lamina associates with other nuclear envelope proteins and plays numerous roles, including maintaining the nuclear shape and structure, assembly and disassembly of the nucleus, heterochromatin organisation, transcriptional regulation and other nuclear functions. Here, we studied the role of A-type lamins in the maturation of rat cerebellar GCs during normal brain development by performing the gene expression profiling of GCs knocked-down for Lamin A. We demonstrated that Lamin A/C has a key role in neural differentiation and GC maturation, also under physiological conditions.

2025-04-09 | GSE247980 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data