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Annual Review of Biochemistry 2012Among organelles, lipid droplets (LDs) uniquely constitute a hydrophobic phase in the aqueous environment of the cytosol. Their hydrophobic core of neutral lipids stores... (Review)
Review
Among organelles, lipid droplets (LDs) uniquely constitute a hydrophobic phase in the aqueous environment of the cytosol. Their hydrophobic core of neutral lipids stores metabolic energy and membrane components, making LDs hubs for lipid metabolism. In addition, LDs are implicated in a number of other cellular functions, ranging from protein storage and degradation to viral replication. These processes are functionally linked to many physiological and pathological conditions, including obesity and related metabolic diseases. Despite their important functions and nearly ubiquitous presence in cells, many aspects of LD biology are unknown. In the past few years, the pace of LD investigation has increased, providing new insights. Here, we review the current knowledge of LD cell biology and its translation to physiology.
Topics: Animals; Cells; Humans; Lipid Metabolism; Lipids; Lipolysis; Metabolic Diseases; Obesity; Organelles
PubMed: 22524315
DOI: 10.1146/annurev-biochem-061009-102430 -
International Journal of Molecular... Apr 2021Cellular senescence and aging result in a reduced ability to manage persistent types of inflammation. Thus, the chronic low-level inflammation associated with aging... (Review)
Review
Cellular senescence and aging result in a reduced ability to manage persistent types of inflammation. Thus, the chronic low-level inflammation associated with aging phenotype is called "inflammaging". Inflammaging is not only related with age-associated chronic systemic diseases such as cardiovascular disease and diabetes, but also skin aging. As the largest organ of the body, skin is continuously exposed to external stressors such as UV radiation, air particulate matter, and human microbiome. In this review article, we present mechanisms for accumulation of senescence cells in different compartments of the skin based on cell types, and their association with skin resident immune cells to describe changes in cutaneous immunity during the aging process.
Topics: Aging; Animals; Cellular Microenvironment; Cellular Senescence; Fibroblasts; Humans; Inflammation; Keratinocytes; Melanocytes; Skin; Skin Physiological Phenomena; Skin Pigmentation
PubMed: 33917737
DOI: 10.3390/ijms22083849 -
The Journal of Clinical Investigation Nov 2023Over the last decade, several organoid models have evolved to acquire increasing cellular, structural, and functional complexity. Advanced lung organoid platforms... (Review)
Review
Over the last decade, several organoid models have evolved to acquire increasing cellular, structural, and functional complexity. Advanced lung organoid platforms derived from various sources, including adult, fetal, and induced pluripotent stem cells, have now been generated, which more closely mimic the cellular architecture found within the airways and alveoli. In this regard, the establishment of novel protocols with optimized stem cell isolation and culture conditions has given rise to an array of models able to study key cellular and molecular players involved in lung injury and repair. In addition, introduction of other nonepithelial cellular components, such as immune, mesenchymal, and endothelial cells, and employment of novel precision gene editing tools have further broadened the range of applications for these systems by providing a microenvironment and/or phenotype closer to the desired in vivo scenario. Thus, these developments in organoid technology have enhanced our ability to model various aspects of lung biology, including pathogenesis of diseases such as chronic obstructive pulmonary disease, pulmonary fibrosis, cystic fibrosis, and infectious disease and host-microbe interactions, in ways that are often difficult to undertake using only in vivo models. In this Review, we summarize the latest developments in lung organoid technology and their applicability for disease modeling and outline their strengths, drawbacks, and potential avenues for future development.
Topics: Endothelial Cells; Induced Pluripotent Stem Cells; Lung; Pluripotent Stem Cells; Organoids
PubMed: 37966116
DOI: 10.1172/JCI170500 -
Nucleic Acids Research Aug 2019Cellular senescence, an integral component of aging and cancer, arises in response to diverse triggers, including telomere attrition, macromolecular damage and...
Cellular senescence, an integral component of aging and cancer, arises in response to diverse triggers, including telomere attrition, macromolecular damage and signaling from activated oncogenes. At present, senescent cells are identified by the combined presence of multiple traits, such as senescence-associated protein expression and secretion, DNA damage and β-galactosidase activity; unfortunately, these traits are neither exclusively nor universally present in senescent cells. To identify robust shared markers of senescence, we have performed RNA-sequencing analysis across eight diverse models of senescence triggered in human diploid fibroblasts (WI-38, IMR-90) and endothelial cells (HUVEC, HAEC) by replicative exhaustion, exposure to ionizing radiation or doxorubicin, and expression of the oncogene HRASG12V. The intersection of the altered transcriptomes revealed 50 RNAs consistently elevated and 18 RNAs consistently reduced across all senescence models, including many protein-coding mRNAs and some non-coding RNAs. We propose that these shared transcriptome profiles will enable the identification of senescent cells in vivo, the investigation of their roles in aging and malignancy and the development of strategies to target senescent cells therapeutically.
Topics: Aging; Antibiotics, Antineoplastic; Cell Line; Cells, Cultured; Cellular Senescence; Doxorubicin; Endothelial Cells; Fibroblasts; Humans; Neoplasms; RNA, Messenger; Radiation, Ionizing; Sequence Analysis, RNA; Transcriptome
PubMed: 31251810
DOI: 10.1093/nar/gkz555 -
Neoplasia (New York, N.Y.) Jan 2015Three-dimensional (3D) in vitro models have been used in cancer research as an intermediate model between in vitro cancer cell line cultures and in vivo tumor. Spherical... (Review)
Review
Three-dimensional (3D) in vitro models have been used in cancer research as an intermediate model between in vitro cancer cell line cultures and in vivo tumor. Spherical cancer models represent major 3D in vitro models that have been described over the past 4 decades. These models have gained popularity in cancer stem cell research using tumorospheres. Thus, it is crucial to define and clarify the different spherical cancer models thus far described. Here, we focus on in vitro multicellular spheres used in cancer research. All these spherelike structures are characterized by their well-rounded shape, the presence of cancer cells, and their capacity to be maintained as free-floating cultures. We propose a rational classification of the four most commonly used spherical cancer models in cancer research based on culture methods for obtaining them and on subsequent differences in sphere biology: the multicellular tumor spheroid model, first described in the early 70s and obtained by culture of cancer cell lines under nonadherent conditions; tumorospheres, a model of cancer stem cell expansion established in a serum-free medium supplemented with growth factors; tissue-derived tumor spheres and organotypic multicellular spheroids, obtained by tumor tissue mechanical dissociation and cutting. In addition, we describe their applications to and interest in cancer research; in particular, we describe their contribution to chemoresistance, radioresistance, tumorigenicity, and invasion and migration studies. Although these models share a common 3D conformation, each displays its own intrinsic properties. Therefore, the most relevant spherical cancer model must be carefully selected, as a function of the study aim and cancer type.
Topics: Animals; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Humans; In Vitro Techniques; Neoplasms; Neoplastic Stem Cells; Radiation Tolerance; Spheroids, Cellular; Tissue Culture Techniques; Tumor Cells, Cultured
PubMed: 25622895
DOI: 10.1016/j.neo.2014.12.004 -
Cell Aug 2011The generation of properly functioning gametes in vitro requires reconstitution of the multistepped pathway of germ cell development. We demonstrate here the generation...
The generation of properly functioning gametes in vitro requires reconstitution of the multistepped pathway of germ cell development. We demonstrate here the generation of primordial germ cell-like cells (PGCLCs) in mice with robust capacity for spermatogenesis. PGCLCs were generated from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) through epiblast-like cells (EpiLCs), a cellular state highly similar to pregastrulating epiblasts but distinct from epiblast stem cells (EpiSCs). Reflecting epiblast development, EpiLC induction from ESCs/iPSCs is a progressive process, and EpiLCs highly competent for the PGC fate are a transient entity. The global transcription profiles, epigenetic reprogramming, and cellular dynamics during PGCLC induction from EpiLCs meticulously capture those associated with PGC specification from the epiblasts. Furthermore, we identify Integrin-β3 and SSEA1 as markers that allow the isolation of PGCLCs with spermatogenic capacity from tumorigenic undifferentiated cells. Our findings provide a paradigm for the first step of in vitro gametogenesis.
Topics: Animals; Cell Culture Techniques; Cell Differentiation; Cell Proliferation; Embryonic Stem Cells; Gene Expression Profiling; Germ Cells; Germ Layers; Induced Pluripotent Stem Cells; Mice; Pluripotent Stem Cells; Spermatogenesis
PubMed: 21820164
DOI: 10.1016/j.cell.2011.06.052 -
Journal of Hepatology Oct 2014The liver has the unique capacity to regenerate in response to a damaging event. Liver regeneration is hereby largely driven by hepatocyte proliferation, which in turn... (Review)
Review
The liver has the unique capacity to regenerate in response to a damaging event. Liver regeneration is hereby largely driven by hepatocyte proliferation, which in turn relies on cell cycling. The hepatocyte cell cycle is a complex process that is tightly regulated by several well-established mechanisms. In vitro, isolated hepatocytes do not longer retain this proliferative capacity. However, in vitro cell growth can be boosted by immortalization of hepatocytes. Well-defined immortalization genes can be artificially overexpressed in hepatocytes or the cells can be conditionally immortalized leading to controlled cell proliferation. This paper discusses the current immortalization techniques and provides a state-of-the-art overview of the actually available immortalized hepatocyte-derived cell lines and their applications.
Topics: Animals; Cell Culture Techniques; Cell Proliferation; Cells, Cultured; Cellular Senescence; Hepatocytes; Humans
PubMed: 24911463
DOI: 10.1016/j.jhep.2014.05.046 -
Cancer Science Mar 2017Recently, many types of in vitro 3-D culture systems have been developed to recapitulate the in vivo growth conditions of cancer. The cancer 3-D culture methods aim to... (Review)
Review
Recently, many types of in vitro 3-D culture systems have been developed to recapitulate the in vivo growth conditions of cancer. The cancer 3-D culture methods aim to preserve the biological characteristics of original tumors better than conventional 2-D monolayer cultures, and include tumor-derived organoids, tumor-derived spheroids, organotypic multicellular spheroids, and multicellular tumor spheroids. The 3-D culture methods differ in terms of cancer cell sources, protocols for cell handling, and the required time intervals. Tumor-derived spheroids are unique because they are purposed for the enrichment of cancer stem cells (CSCs) or cells with stem cell-related characteristics. These spheroids are grown as floating spheres and have been used as surrogate systems to evaluate the CSC-related characteristics of solid tumors in vitro. Because eradication of CSCs is likely to be of clinical importance due to their association with the malignant nature of cancer cells, such as tumorigenicity or chemoresistance, the investigation of tumor-derived spheroids may provide invaluable clues to fight against cancer. Spheroid cultures have been established from cancers including glioma, breast, colon, ovary, and prostate cancers, and their biological and biochemical characteristics have been investigated by many research groups. In addition to the investigation of CSCs, tumor-derived spheroids may prove to be instrumental for a high-throughput screening platform or for the cultivation of CSC-related tumor cells found in the circulation or body fluids.
Topics: Cell Culture Techniques; Humans; Neoplasms; Neoplastic Stem Cells; Spheroids, Cellular; Tumor Cells, Cultured
PubMed: 28064442
DOI: 10.1111/cas.13155 -
Nature Reviews. Molecular Cell Biology Mar 2021Biomolecular condensates are found throughout eukaryotic cells, including in the nucleus, in the cytoplasm and on membranes. They are also implicated in a wide range of... (Review)
Review
Biomolecular condensates are found throughout eukaryotic cells, including in the nucleus, in the cytoplasm and on membranes. They are also implicated in a wide range of cellular functions, organizing molecules that act in processes ranging from RNA metabolism to signalling to gene regulation. Early work in the field focused on identifying condensates and understanding how their physical properties and regulation arise from molecular constituents. Recent years have brought a focus on understanding condensate functions. Studies have revealed functions that span different length scales: from molecular (modulating the rates of chemical reactions) to mesoscale (organizing large structures within cells) to cellular (facilitating localization of cellular materials and homeostatic responses). In this Roadmap, we discuss representative examples of biochemical and cellular functions of biomolecular condensates from the recent literature and organize these functions into a series of non-exclusive classes across the different length scales. We conclude with a discussion of areas of current interest and challenges in the field, and thoughts about how progress may be made to further our understanding of the widespread roles of condensates in cell biology.
Topics: Animals; Biochemical Phenomena; Cell Physiological Phenomena; Cytoplasm; Eukaryotic Cells; Humans; Macromolecular Substances; Multiprotein Complexes; Organelles; Protein Aggregates
PubMed: 33169001
DOI: 10.1038/s41580-020-00303-z -
Cell Reports Feb 2019Human enteroids-epithelial spheroids derived from primary gastrointestinal tissue-are a promising model to study pathogen-epithelial interactions. However, accessing the...
Human enteroids-epithelial spheroids derived from primary gastrointestinal tissue-are a promising model to study pathogen-epithelial interactions. However, accessing the apical enteroid surface is challenging because it is enclosed within the spheroid. We developed a technique to reverse enteroid polarity such that the apical surface everts to face the media. Apical-out enteroids maintain proper polarity and barrier function, differentiate into the major intestinal epithelial cell (IEC) types, and exhibit polarized absorption of nutrients. We used this model to study host-pathogen interactions and identified distinct polarity-specific patterns of infection by invasive enteropathogens. Salmonella enterica serovar Typhimurium targets IEC apical surfaces for invasion via cytoskeletal rearrangements, and Listeria monocytogenes, which binds to basolateral receptors, invade apical surfaces at sites of cell extrusion. Despite different modes of entry, both pathogens exit the epithelium within apically extruding enteroid cells. This model will enable further examination of IECs in health and disease.
Topics: Cell Culture Techniques; Cell Differentiation; Cell Polarity; Epithelial Cells; Fatty Acids; Host-Pathogen Interactions; Humans; Intestinal Mucosa; Listeria monocytogenes; Models, Biological; Salmonella typhimurium; Spheroids, Cellular
PubMed: 30811997
DOI: 10.1016/j.celrep.2019.01.108