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At least 19 recordsLinked to original sources
PubMed2025

The molecular basis of lamin-specific chromatin interactions.

In the cell nucleus, chromatin is anchored to the nuclear lamina, a network of lamin filaments and binding proteins that underly the inner nuclear membrane. The nuclear lamina is involved in chromatin organization through the interaction of lamina-associated domains within the densely packed heterochromatin regions. Using cryo-focused ion beam milling in conjunction with cryo-electron tomography, we analyzed the distribution of nucleosomes at the lamin-chromatin interface at the nanometer scale. Depletion of lamins A and C reduced nucleosome concentration at the nuclear periphery, while B-type lamin depletion contributed to nucleosome density in proximity to the lamina but not further away. We then investigated whether specific lamins can mediate direct interactions with chromatin. Using cryo-electron microscopy, we identified a specific binding motif of the lamin A tail domain that interacts with nucleosomes, distinguishing it from the other lamin isoforms. Furthermore, we examined chromatin structure dynamics using a genome-wide analysis that revealed lamin-dependent macroscopic-scale alterations in gene expression and chromatin remodeling. Our findings provide detailed insights into the dynamic and structural interplay between lamin isoforms and chromatin, molecular interactions that shape chromatin architecture and epigenetic regulation.

Nucleosomes↗
PubMed1979

Properties of neurons in cat's dorsal lateral geniculate nucleus: a comparison between medial interlaminar and laminated parts of the nucleus.

We studied the receptive field properties of 460 cells in the cat's dorsal lateral geniculate nucleus (LGNd), 108 cells were located in the medial interlaminar nucleus (MIN) and 352 in the laminated part of the LGNd. In both the MIN and laminated parts of the LGNd, relay cells belonging to all three functional classes (W, X and Y) have been identified. Of cells in the laminated LGNd, about 32.5% were Y cells, about 54.5% were X cells and about 8.5% were W cells. By contrast, in the MIN, about 84% were Y cells, only about 4.5% being X cells and about 7.5%, W cells. In the laminated LGNd, Y cells represented 25% of cells with receptive fields near the area centralis (0-3 degrees eccentricity group) and about 42% in the group of cells with the most peripherally located receptive fields (20-40 degrees eccentricity group). A similar but much weaker trend was observed in the MIN. In the laminated LGNd but not in the MIN the receptive field center sizes increased with increasing eccentricity of receptive field position. At any eccentricity, receptive field centers of MIN Y cells tended to be larger than those of Y cells in the laminated LGNd. Response latency ranges to orthodromic and antidromic stimulation were the same for cells located in the laminated LGNd and those in the MIN. However, the mean response latency to stimulation of the optic chiasm was significantly shorter for Y cells in MIN than for Y cells in the laminated LGNd. Our results suggest that the most numerous cells observed histologically in the MIN, class 1 cells of Guillery ('66) are morphological equivalents of Y cells.

Animals↗
PubMed2025

Nuclear-lamin-guided plastic positioning and folding of the human genome.

The human genome exhibits a highly ordered hierarchical architecture, yet the mechanisms governing its large-scale organization remain poorly understood. Here, we generate lamin single-, double-, and triple-knockout human embryonic and mesenchymal stem cells (hESCs and hMSCs) to investigate the role of lamins in the spatial organization of the human genome. Complete lamin depletion in hMSCs triggers extensive genome repositioning, disrupts chromosome territories, and dissolves long-range compartment clustering and mega-loops. Lamin loss affects both the nuclear periphery and interior, causing partial inversion and dispersion of nuclear speckles, accompanied by reduced global transcription and impaired stem cell homeostasis. Re-expression of wild-type lamin A, which interacts with the speckle scaffold protein SON, partially restores the organizational and transcriptional defects, while the disease-associated E161K mutant disrupts SON binding and shows limited recovery. Our results elucidate the multifaceted roles of lamins in nuclear organization and link their dysfunction to the pathogenesis of laminopathies.

Humans↗
PubMed2026

Telomeres in Lamin-A-depleted cells exhibit directed motion and dynamic coherence.

Investigating the dynamics of chromatin loci and the factors that influence them provides valuable insights into the organization and functionality of the genome within the cell nucleus. We control the expression of Lamin-A, an important organizer of chromatin and nuclear structure. By simultaneously tracking hundreds of telomeres in Lamin-A knockout (KO) and wild-type (WT) nuclei, we find that telomere motion in Lamin-A-depleted cells is both faster and more directed on micrometer scales, comparable to the size of chromosome territories. In contrast, telomere trajectories in WT cells exhibit pronounced anti-persistent behavior, consistent with caging by the surrounding chromatin environment. We further observe correlated motion between distinct telomeres in both WT and KO cells, with significantly stronger correlations in the KO case, indicating enhanced collective behavior. These correlations reflect cross-correlations among different loci rather than temporal correlations along individual trajectories. Together, these findings highlight the central role of Lamin-A in regulating both local confinement and collective telomere dynamics.

Telomere↗
PubMed1976

Concentric laminated bodies. Ultrastructural demonstration of muscle fiber type specificity.

Concentric laminated bodies were identified in the skeletal muscle of 3 children affected by muscle weakness and hypotonia with probable cerebral involvement. The mean Z-line and M-line widths from each of 11 muscle fibers containing the concentric laminated bodies were calculated. The mean Z-line widths were 61-81 nm and the mean M-line widths from 7 out of 11 fibers were 54-65 nm. According to our present system of fiber typing, the majority of these fibers would be classified as subtype IIB. The possible pathogenesis and fiber type specificity of the concentric laminated body is discussed.

Child, Preschool↗
PubMed2026

Lamin-ating the genome: quantitative gatekeeping of replication initiation.

Discovered in the 1970s, nuclear lamins control chromatin organization and are linked to many diseases. Zhang et al. now find that lamin A/C quantitatively constrains DNA replication initiation by limiting chromatin accessibility and sequestering proliferating cell nuclear antigen, extending lamin's long-known role in replication to the control of origin firing.

Journal Article↗
PubMed1978

A new myelin-like laminated body found in two cases of pulmonary alveolar proteinosis.

Electron microscopic observations were made on lung tissue, broncho-pulmonary lavage fluid and sputum in 2 cases of pulmonary alveolar proteinosis. Diagnosis was established by open lung biopsy in both cases. In Case 1 the electron microscopic samples were obtained from the surgical specimen. In Case 2 an electron microscopic observation was made only on the lavage fluid and sputum. The alveolar air spaces were full of amorphous or fine granular-appearing material intermingled with two kinds of laminated bodies (abbreviated to "Lamella A" and "Lamella B"). Lamella A, about 0.2 approximately 4 micrometer in diameter, presented a concentric laminated structure with approximately 300 A periodicity and was found in the alveolar air spaces, lung washings and sputum. It corresponded to what has hitherto been reported in the same disease and was always located outside the cells. Lamella B showed a laminated structure of high electron density, approximately 50 A in periodicity, usually looking like a concentric circle with a diameter of 0.5 micrometer or less. It was intensely stained with methenamine silver. It was mainly observed in mesenchymal cells of the alveolar septa and free macrophages in the alveolar air spaces, although it also occurred in the type I and type II alveolar epithelial cells. Furthermore, the Lamella B could be found in the alveolar air spaces outside the cells and in the bronchopulmonary lavage fluid. This body has not been demonstrated previously and, although its significance in this disease is still uncertain, the structural similarity of the Lamella B to the intra-alveolar material suggests a possible role of it in the production of intra-alveolar material.

Adolescent↗
PubMed1978

Cardiovascular, acid-base, electrolyte, and plasma volume changes in ponies developing alimentary laminitis.

Twelve Shetland ponies were fed a high-starch ration. Seven ponies which had a transitory metabolic acidosis developed laminitis 56 hours (+/- 3.5, SEM) after overfeeding. These ponies also developed persistent hypokalemia, hyperthermia, and increased heart rate 24 hours before the onset of lameness. Serum sodium, serum chloride, hematocrit, plasma volume, and blood volume were unchanged. At the onset of clinical signs of laminitis, cardiac output and blood pressure increased, but total peripheral resistance was unchanged. None of the measured or calculated values predicted the onset of laminitis. Hypertension appeared to be a response to, rather than a cause of, lameness. Three of the remaining ponies apparently died of shock 29.3 +/- 2.7 hours after overfeeding. All 3 had severe metabolic acidosis; decreased cardiac output, systemic arterial pressure, and plasma volume; and increased hematocrit, total peripheral resistance, and pulmonary vascular resistance. The 11th pony was unaffected and the 12th pony was euthanatized.

Acid-Base Imbalance↗
PubMed2025

Kin17 promotes rDNA transcription, ribosomal biogenesis, and cortical lamination.

During brain development, neural progenitor cells (NPCs) undergo rapid division, necessitating efficient ribosomal biogenesis for proliferation. Yet, the regulatory mechanisms remain largely elusive. Here, we report that the DNA binding protein Kin17 exhibits development-dependent expression and plays a vital role in embryonic development. Complete loss of Kin17 in mice leads to embryonic lethality, while Kin17 depletion specifically in NPCs allows embryonic survival but results in reduced brain size and cortical lamination defects. Our findings demonstrate that these cortical malformation stems from impaired NPC proliferation and differentiation. Mechanistically, we show that Kin17 binds to the promoter region of rDNA, sequentially recruiting NCL and Polr1a, thereby promoting rDNA transcription. Consequently, Kin17 facilitates ribosome biogenesis and protein translation in NPCs. This study underscores a critical role of Kin17 in promoting rDNA transcription and ribosomal biogenesis in NPCs during brain development, which is essential for proper cortical lamination.

Animals↗
PubMed2025

Radiation symptoms resemble laminopathies and the physical underlying cause may sit at the lamin A C-terminus.

Ionizing radiation causes three divergent effects in the human body: On one side, tissue death (= deterministic effects) sets on, on the other side, mutations and cancer growth (= stochastic effects) can occur. In recent years, the additional phenomenon of accelerated aging has come to light. In the following, we argue that these seemingly contradictory radiation responses namely: (i) increased cancer growth, (ii) ablation of cancer tissue or (iii) deterministic senescence, share an underlying cause from damage at the lamin A C-terminus. In other words, besides the typically described genomic radiation impact, we propose an additional destabilization pathway via oxidation at the nuclear envelope. We propose five concrete hypotheses that draw a direct mechanistic model from radiation damage and cellular oxidative stress, to micronuclei and clinical symptoms. In conjunction with lamin B compensation, we might be able to explain why deterministic or stochastic responses dominate. If our model holds true, a novel target for radiotherapeutics and radiooncology arises, and a rationale to closer connect laminopathy and radioprotection research.

Animals↗
PubMed1978

The retino-geniculo-cortical pathway in Callithrix. I. Intraspecific variations in the lamination pattern of the lateral geniculate nucleus.

Injections of tritiated tracer precursors into one eye revealed a highly variable lamination pattern of the LGN in the marmoset Callithrix. In one specimen, only four cell layers were apparent with some indication of further differentiation. In a second specimen, six almost complete relay layers were found in the occipital portion of the LGN. Three other animals showed stages between these two extremes. The lamination pattern of Callithrix thun represents an intermediate stage between a four-layered LGN suggested as the basic primate pattern, and the advanced six-layered LGN of most other anthropoid monkeys. In addition, bilateral retinal terminations were found consistently in layer 0, and contralateral terminations in a narrow band between the magnocellular and parvocellular portions of the nucleus, and within the interlaminar zone which separates the two magnocellular layers.

Animals↗
PubMed1978

Changes in the caecal flora associated with the onset of laminitis.

Caecal fluid samples collected 8 and 24 hours after carbohydrate overload were quantitatively compared to control samples in terms of aerobic and anaerobic bacteria. Concomitant increases in lactic acid-producing bacteria and decreases in Gram negative bacteria were substantiated during the onset of acute laminitis. Progressive decreases in caecal fluid pH were also quantitated. Although endotoxin assays of caecal fluid and blood were not done, the caecal flora changes suggest its presence during the onset of acute laminitis.

Animals↗
PubMed1979

Cylindrical laminated bodies in nickel-subsulphide-induced rhabdomyosarcoma in rabbits.

The induction of rabbit rhabdomyosarcoma was obtained after intramuscular implantation of a large quantity of very pure nickel subsulphide, though until the present time the rabbit was considered refractory to Ni3S2 tumorigenesis. These tumors are similar to those induced in rats under the same conditions. Four different cell types were observed: small polygonal cells, small elongated cells, giant cells, and mature myofibers. Electron microscopy reveals a complete disorientation of myofibrils in mature myoblasts. Giant cells appear by pluripolar endomitosis and always contain myofibrillar structures, but M-lines and Z-lines are not present in these cells. Cylindrical laminated bodies were observed very often in all four cell types. They are formed of 4 nm fibrils arranged in crossed position in each lamella. Some of these paracrystalline structures were also observed in nuclei. The laminated bodies are considered to be abnormal formations of contractile proteins produced during tumoral myofibrillar differentiation.

Animals↗
PubMed2025

Lamin A/C loss promotes R-loop-mediated genomic instability and poor survival in small-cell lung cancer.

Lamin A/C (LMNA), a key component of the nuclear envelope, is essential for maintaining nuclear integrity and genome organization [W. Xie et al., Curr. Biol. 26, 2651-2658 (2016)]. While LMNA dysregulation has been implicated in genomic instability across cancer and aging, the underlying mechanisms remain poorly understood [S. Graziano et al., Nucleus 9, 258-275 (2018)]. Here, we define a mechanistic role for LMNA in preserving genome stability in small-cell lung cancer (SCLC), a malignancy marked by extreme genomic instability [N. Takahashi et al., Cancer Res. Commun. 2, 503-517 (2022)]. LMNA depletion promotes R-loop accumulation, transcription-replication conflicts, replication stress, DNA breaks, and micronuclei formation. Mechanistically, LMNA deficiency disrupts nuclear pore complex organization, specifically reducing phenylalanine-glycine (FG)-nucleoporin incorporation, resulting in impaired RNA export and nuclear retention of RNA. LMNA expression is repressed by EZH2 and reexpressed during SCLC differentiation from neuroendocrine (NE) to non-NE states, and low LMNA levels correlate with poor clinical outcomes. These findings establish LMNA as a key regulator of nuclear transport and genome integrity, linking nuclear architecture to SCLC progression and therapeutic vulnerability.

Lamin Type A↗
PubMed1979

Focal laminate segments in cytoplasmic processes of mouse myocardial fibroblasts.

In mouse ventricular myocardium, we have found unusual fibroblasts whose cellular processes in some regions are particularly flattened and which contain linearly-arranged, electron-opaque structures ('central laminae"). The morphology of these focal laminate segments of fibroblast processes suggests that the intracellular laminae are adhesive entities which hold the plasmalemmata above and below them in close parallel apposition for short distances.

Animals↗
PubMed2025

Lamin A/C Deficiency Drives Genomic Instability and Poor Survival in Small-Cell Lung Cancer through Increased R-loop Accumulation.

Lamin A/C (LMNA), a key component of the nuclear envelope, is essential for maintaining nuclear integrity and genome organization [1]. While LMNA dysregulation has been implicated in genomic instability across cancer and aging, the underlying mechanisms remain poorly understood [2]. Here, we investigate LMNA's role in small-cell lung cancer (SCLC), a highly aggressive malignancy characterized by extreme genomic instability [3, 4]. We demonstrate that LMNA depletion promotes R-loop accumulation, transcription-replication conflicts, replication stress, DNA breaks, and micronuclei formation. Mechanistically, LMNA loss disrupts nuclear pore complex distribution, reducing phenylalanine-glycine (FG)-nucleoporin incorporation and impairing RNA export efficiency. Furthermore, we show that LMNA expression is epigenetically repressed by EZH2 during SCLC differentiation from neuroendocrine (NE) to non-NE states. Clinically, low LMNA levels correlate with significantly worse survival in SCLC patients. These findings uncover a novel role for LMNA in safeguarding genome integrity and shaping tumor heterogeneity, with broad implications for cancer and aging.

Biological Sciences↗
PubMed1979

Trial of a laminated material to reduce glare in cataract.

A recently-introduced laminated material which accepts light only over a small angle on either side of the normal was compared to standard Polaroid sunglasses. A preliminary trial failed to show any superiority of the new material in reducing glare for patients with moderate cataract.

Aged↗