Results and Problems in Cell Differentiation最新文献

{"title":"Nucleolar Organizer Regions as Transcription-Based Scaffolds of Nucleolar Structure and Function.","authors":"Alexandria J Cockrell,&nbsp;Jennifer L Gerton","doi":"10.1007/978-3-031-06573-6_19","DOIUrl":"https://doi.org/10.1007/978-3-031-06573-6_19","url":null,"abstract":"<p><p>Eukaryotic genomes maintain multiple copies of ribosomal DNA gene repeats in tandem arrays to provide sufficient ribosomal RNAs to make ribosomes. These DNA repeats are the most highly transcribed regions of the genome, with dedicated transcriptional machinery to manage the enormous task of producing more than 50% of the total RNA in a proliferating cell. The arrays are called nucleolar organizer regions (NORs) and constitute the scaffold of the nucleolar compartment, where ribosome biogenesis occurs. Advances in molecular and cellular biology have brought great insights into how these arrays are transcribed and organized within genomes. Much of their biology is driven by their high transcription level, which has also driven the development of unique methods to understand rDNA gene activity, beginning with classic techniques such as silver staining and Miller spreads. However, the application of modern methodologies such as CRISPR gene editing, super-resolution microscopy, and long-read sequencing has enabled recent advances described herein, with many more discoveries possible soon. This chapter highlights what is known about NOR transcription and organization and the techniques applied historically and currently. Given the potential for NORs to impact organismal health and disease, as highlighted at the end of the chapter, the field must continue to develop and apply innovative analysis to understand genetic, epigenetic, and organizer properties of the ribosomal DNA repeats.</p>","PeriodicalId":39320,"journal":{"name":"Results and Problems in Cell Differentiation","volume":" ","pages":"551-580"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40673082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Aspects of Sperm Chromatin Organization.","authors":"Jordi Ribas-Maynou,&nbsp;Hieu Nguyen,&nbsp;Hongwen Wu,&nbsp;W Steven Ward","doi":"10.1007/978-3-031-06573-6_10","DOIUrl":"https://doi.org/10.1007/978-3-031-06573-6_10","url":null,"abstract":"<p><p>Sperm nuclei present a highly organized and condensed chromatin due to the interchange of histones by protamines during spermiogenesis. This high DNA condensation leads to almost inert chromatin, with the impossibility of conducting gene transcription as in most other somatic cells. The major chromosomal structure responsible for DNA condensation is the formation of protamine-DNA toroids containing 25-50 kilobases of DNA. These toroids are connected by toroid linker regions (TLR), which attach them to the nuclear matrix, as matrix attachment regions (MAR) do in somatic cells. Despite this high degree of condensation, evidence shows that sperm chromatin contains vulnerable elements that can be degraded even in fully condensed chromatin, which may correspond to chromatin regions that transfer functionality to the zygote at fertilization. This chapter covers an updated review of our model for sperm chromatin structure and its potential functional elements that affect embryo development.</p>","PeriodicalId":39320,"journal":{"name":"Results and Problems in Cell Differentiation","volume":" ","pages":"295-311"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9671218/pdf/nihms-1849442.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40672121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular Polarity Transmission to the Nucleus.","authors":"Paulina Nastały,&nbsp;Paolo Maiuri","doi":"10.1007/978-3-031-06573-6_21","DOIUrl":"https://doi.org/10.1007/978-3-031-06573-6_21","url":null,"abstract":"<p><p>Polarity is an intrinsic and fundamental property of unicellular organisms and, as well, of single cells in multicellular ones. It can be defined as asymmetric cell organization that is self-reinforced and maintained by appropriate signaling. While cellular polarity is widely studied at the membrane and cytoplasmic level, if and how it is transmitted to the nucleus is still a matter of research and discussion. However, there is growing evidence of polarity transmission from the cell to the nucleus. In this chapter, we discuss recent reports on nuclear polarity and involvement of potential molecular players including emerin, nesprins, and nuclear F-actin which may play a significant role in establishment of this phenomenon.</p>","PeriodicalId":39320,"journal":{"name":"Results and Problems in Cell Differentiation","volume":" ","pages":"597-606"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40673011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone Modifications in Mouse Pronuclei and Consequences for Embryo Development.","authors":"Ewa Borsuk,&nbsp;Julia Michalkiewicz,&nbsp;Jacek Z Kubiak,&nbsp;Malgorzata Kloc","doi":"10.1007/978-3-031-06573-6_14","DOIUrl":"https://doi.org/10.1007/978-3-031-06573-6_14","url":null,"abstract":"<p><p>Epigenetic marks, such as DNA methylation and posttranslational modifications of core histones, are the key regulators of gene expression. In the mouse, many of these marks are erased during gamete formation and must be introduced de novo after fertilization. Some of them appear synchronously, but the others are deposited asynchronously and/or remain differently distributed on maternal and paternal chromatin. Although the mechanisms regulating these processes are not entirely understandable, it is commonly accepted that epigenetic reprogramming occurring during the first cell cycle of a mouse embryo is crucial for its further development. This chapter focuses on selected epigenetic modifications, such as DNA methylation, the introduction of histone variants, histones acetylation, phosphorylation, and methylation. Properly depositing these marks on maternal and paternal chromatin is crucial for normal embryonic development.</p>","PeriodicalId":39320,"journal":{"name":"Results and Problems in Cell Differentiation","volume":" ","pages":"397-415"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40673077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How Genomes Emerge, Function, and Evolve: Living Systems Emergence-Genotype-Phenotype-Multilism-Genome/Systems Ecology.","authors":"Tobias A Knoch","doi":"10.1007/978-3-031-06573-6_4","DOIUrl":"https://doi.org/10.1007/978-3-031-06573-6_4","url":null,"abstract":"<p><p>What holds together the world in its innermost, what life is, how it emerges, functions, and evolves, has not only been an epic matter of endless romantic sunset poetry and philosophy, but also manifests explicitly in its perhaps most central organization unit-genomes. Their 3D architecture and dynamics, including the interaction networks of regulatory elements, obviously co-evolved as inseparable systems allowing the physical storage, expression, and replication of genetic information. Since we were able to fill finally the much-debated centennial gaps in their 3D architecture and dynamics, now entire new perspectives open beyond epigenetics reaching as far as a general understanding of living systems: besides the previously known DNA double helix and nucleosome structure, the latter compact into a chromatin quasi-fibre folded into stable loops forming stable multi-loop aggregates/rosettes connected by linkers, creating hence the again already known chromosome arms and entire chromosomes forming the cell nucleus. Instantly and for the first time this leads now to a consistent and cross-proven systems statistical mechanics genomics framework elucidating genome intrinsic function and regulation including various components. It balances stability/flexibility ensuring genome integrity, enabling expression/regulation of genetic information, as well as genome replication/spread. Furthermore, genotype and phenotype are multiplisticly entangled being evolutionarily the outcome of both Darwinian natural selection and Lamarckian self-referenced manipulation-all embedded in even broader genome ecology (autopoietic) i(!)n- and environmental scopes. This allows formulating new meta-level functional semantics of genomics, i.e. notions as communication of genes, genomes, and information networks, architectural and dynamic spaces for creativity and innovation, or genomes as central geno-/phenotype entanglements. Beyond and most fundamentally, the paradoxical-seeming local equilibrium substance stability in its entity though far from a universal heat-death-like equilibrium is solved, and system irreversibility, time directionality, and thus the emergence of existence are clarified. Consequently, real deep understandings of genomes, life, and complex systems in general appear in evolutionary perspectives as well as from systems analyses, via system damage/disease (its repair/cure and manipulation) as far as the understanding of extraterrestrial life, the de novo creation and thus artificial life, and even the raison d'etre.</p>","PeriodicalId":39320,"journal":{"name":"Results and Problems in Cell Differentiation","volume":" ","pages":"103-156"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40474096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear Morphological Abnormalities in Cancer: A Search for Unifying Mechanisms.","authors":"Ishita Singh,&nbsp;Tanmay P Lele","doi":"10.1007/978-3-031-06573-6_16","DOIUrl":"https://doi.org/10.1007/978-3-031-06573-6_16","url":null,"abstract":"<p><p>Irregularities in nuclear shape and/or alterations to nuclear size are a hallmark of malignancy in a broad range of cancer types. Though these abnormalities are commonly used for diagnostic purposes and are often used to assess cancer progression in the clinic, the mechanisms through which they occur are not well understood. Nuclear size alterations in cancer could potentially arise from aneuploidy, changes in osmotic coupling with the cytoplasm, and perturbations to nucleocytoplasmic transport. Nuclear shape changes may occur due to alterations to cell-generated mechanical stresses and/or alterations to nuclear structural components, which balance those stresses, such as the nuclear lamina and chromatin. A better understanding of the mechanisms underlying abnormal nuclear morphology and size may allow the development of new therapeutics to target nuclear aberrations in cancer.</p>","PeriodicalId":39320,"journal":{"name":"Results and Problems in Cell Differentiation","volume":"70 ","pages":"443-467"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9722227/pdf/nihms-1852107.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10516705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Multimorbidity into a Whole-Body Understanding of Disease Using Spatial Genomics.","authors":"Sreemol Gokuladhas,&nbsp;Roan E Zaied,&nbsp;William Schierding,&nbsp;Sophie Farrow,&nbsp;Tayaza Fadason,&nbsp;Justin M O'Sullivan","doi":"10.1007/978-3-031-06573-6_5","DOIUrl":"https://doi.org/10.1007/978-3-031-06573-6_5","url":null,"abstract":"<p><p>Multimorbidity is characterized by multidimensional complexity emerging from interactions between multiple diseases across levels of biological (including genetic) and environmental determinants and the complex array of interactions between and within cells, tissues and organ systems. Advances in spatial genomic research have led to an unprecedented expansion in our ability to link alterations in genome folding with changes that are associated with human disease. Studying disease-associated genetic variants in the context of the spatial genome has enabled the discovery of transcriptional regulatory programmes that potentially link dysregulated genes to disease development. However, the approaches that have been used have typically been applied to uncover pathological molecular mechanisms occurring in a specific disease-relevant tissue. These forms of reductionist, targeted investigations are not appropriate for the molecular dissection of multimorbidity that typically involves contributions from multiple tissues. In this perspective, we emphasize the importance of a whole-body understanding of multimorbidity and discuss how spatial genomics, when integrated with additional omic datasets, could provide novel insights into the molecular underpinnings of multimorbidity.</p>","PeriodicalId":39320,"journal":{"name":"Results and Problems in Cell Differentiation","volume":" ","pages":"157-187"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40672118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scaling Relationship in Chromatin as a Polymer.","authors":"Takahiro Sakaue,&nbsp;Akatsuki Kimura","doi":"10.1007/978-3-031-06573-6_8","DOIUrl":"https://doi.org/10.1007/978-3-031-06573-6_8","url":null,"abstract":"<p><p>Genomic DNA, which controls genetic information, is stored in the cell nucleus in eukaryotes. Chromatin moves dynamically in the nucleus, and this movement is closely related to the function of chromatin. However, the driving force of chromatin movement, its control mechanism, and the functional significance of movement are unclear. In addition to biochemical and genetic approaches such as identification and analysis of regulators, approaches based on the physical properties of chromatin and cell nuclei are indispensable for this understanding. In particular, the idea of polymer physics is expected to be effective. This paper introduces our efforts to combine biological experiments on chromatin kinetics with theoretical analysis based on polymer physics.</p>","PeriodicalId":39320,"journal":{"name":"Results and Problems in Cell Differentiation","volume":" ","pages":"263-277"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40672119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Nuclear Actin in Genome Organization and Gene Expression Regulation During Differentiation.","authors":"Syed Raza Mahmood,&nbsp;Nadine Hosny El Said,&nbsp;Piergiorgio Percipalle","doi":"10.1007/978-3-031-06573-6_22","DOIUrl":"https://doi.org/10.1007/978-3-031-06573-6_22","url":null,"abstract":"<p><p>In the cell nucleus, actin participates in numerous essential processes. Actin is involved in chromatin as part of specific ATP-dependent chromatin remodeling complexes and associates with the RNA polymerase machinery to regulate transcription at multiple levels. Emerging evidence has also shown that the nuclear actin pool controls the architecture of the mammalian genome playing an important role in its hierarchical organization into transcriptionally active and repressed compartments, contributing to the clustering of RNA polymerase II into transcriptional hubs. Here, we review the most recent literature and discuss how actin involvement in genome organization impacts the regulation of gene programs that are activated or repressed during differentiation and development. As in the cytoplasm, we propose that nuclear actin is involved in key nuclear tasks in complex with different types of actin-binding proteins that regulate actin function and bridge interactions between actin and various nuclear components.</p>","PeriodicalId":39320,"journal":{"name":"Results and Problems in Cell Differentiation","volume":" ","pages":"607-624"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40673012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simulation of Different Three-Dimensional Models of Whole Interphase Nuclei Compared to Experiments - A Consistent Scale-Bridging Simulation Framework for Genome Organization.","authors":"Tobias A Knoch","doi":"10.1007/978-3-031-06573-6_18","DOIUrl":"https://doi.org/10.1007/978-3-031-06573-6_18","url":null,"abstract":"<p><p>The three-dimensional architecture of chromosomes, their arrangement, and dynamics within cell nuclei are still subject of debate. Obviously, the function of genomes-the storage, replication, and transcription of genetic information-has closely coevolved with this architecture and its dynamics, and hence are closely connected. In this work a scale-bridging framework investigates how of the 30 nm chromatin fibre organizes into chromosomes including their arrangement and morphology in the simulation of whole nuclei. Therefore, mainly two different topologies were simulated with corresponding parameter variations and comparing them to experiments: The Multi-Loop-Subcompartment (MLS) model, in which (stable) small loops form (stable) rosettes, connected by chromatin linkers, and the Random-Walk/Giant-Loop (RW/GL) model, in which large loops are attached to a flexible non-protein backbone, were simulated for various loop and linker sizes. The 30 nm chromatin fibre was modelled as a polymer chain with stretching, bending and excluded volume interactions. A spherical boundary potential simulated the confinement to nuclei with different radii. Simulated annealing and Brownian Dynamics methods were applied in a four-step decondensation procedure to generate from metaphase decondensated interphase configurations at thermodynamical equilibrium. Both the MLS and the RW/GL models form chromosome territories, with different morphologies: The MLS rosettes result in distinct subchromosomal domains visible in electron and confocal laser scanning microscopic images. In contrast, the big RW/GL loops lead to a mostly homogeneous chromatin distribution. Even small changes of the model parameters induced significant rearrangements of the chromatin morphology. The low overlap of chromosomes, arms, and subchromosomal domains observed in experiments agrees only with the MLS model. The chromatin density distribution in CLSM image stacks reveals a bimodal behaviour in agreement with recent experiments. Combination of these results with a variety of (spatial distance) measurements favour an MLS like model with loops and linkers of 63 to 126 kbp. The predicted large spaces between the chromatin fibres allow typically sized biological molecules to reach nearly every location in the nucleus by moderately obstructed diffusion and is in disagreement with the much simplified assumption that defined channels between territories for molecular transport as in the Interchromosomal Domain (ICD) hypothesis exist and are necessary for transport. All this is also in agreement with recent selective high-resolution chromosome interaction capture (T2C) experiments, the scaling behaviour of the DNA sequence, the dynamics of the chromatin fibre, the diffusion of molecules, and other measurements. Also all other chromosome topologies can in principle be excluded. In summary, polymer simulations of whole nuclei compared to experimental data not only clearly favour only a stable loop aggre","PeriodicalId":39320,"journal":{"name":"Results and Problems in Cell Differentiation","volume":" ","pages":"495-549"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40673080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}