Differing molecular mechanisms appear to underlie early toxicity of prefibrillar HypF-N aggregates to different cell types

Embryonic stem cells (ESCs) have the extraordinary properties to indefinitely proliferate and self-renew in culture to produce different cell progeny through differentiation. This latter process recapitulates embryonic development and requires rounds of the epithelial–mesenchymal transition (EMT). EMT is characterized by the loss of the epithelial features and the acquisition of the typical phenotype of the mesenchymal cells. In pathological conditions, EMT can confer stemness or stem-like phenotypes, playing a role in the tumorigenic process. Cancer stem cells (CSCs) represent a subpopulation, found in the tumor tissues, with stem-like properties such as uncontrolled proliferation, self-renewal, and ability to differentiate into different cell types. ESCs and CSCs share numerous features (pluripotency, self-renewal, expression of stemness genes, and acquisition of epithelial–mesenchymal features), and most of them are under the control of microRNAs (miRNAs). These small molecules have relevant roles during both embryogenesis and cancer development. The aim of this review was to recapitulate molecular mechanisms shared by ESCs and CSCs, with a special focus on the recently identified classes of microRNAs (noncanonical miRNAs, mirtrons, isomiRs, and competitive endogenous miRNAs) and their complex functions during embryogenesis and cancer development.

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Filopodyan: An open-source pipeline for the analysis of filopodia

The Journal of Cell Biology ◽

10.1083/jcb.201705113 ◽

2017 ◽

Vol 216 (10) ◽

pp. 3405-3422 ◽

Cited By ~ 14

Author(s):

Vasja Urbančič ◽

Richard Butler ◽

Benjamin Richier ◽

Manuel Peter ◽

Julia Mason ◽

...

Keyword(s):

Molecular Mechanisms ◽

Dynamic Properties ◽

Cell Types ◽

Molecular Heterogeneity ◽

Interactive Editing ◽

Motile Cells ◽

Different Cell Types ◽

Neuronal Growth Cones

Filopodia have important sensory and mechanical roles in motile cells. The recruitment of actin regulators, such as ENA/VASP proteins, to sites of protrusion underlies diverse molecular mechanisms of filopodia formation and extension. We developed Filopodyan (filopodia dynamics analysis) in Fiji and R to measure fluorescence in filopodia and at their tips and bases concurrently with their morphological and dynamic properties. Filopodyan supports high-throughput phenotype characterization as well as detailed interactive editing of filopodia reconstructions through an intuitive graphical user interface. Our highly customizable pipeline is widely applicable, capable of detecting filopodia in four different cell types in vitro and in vivo. We use Filopodyan to quantify the recruitment of ENA and VASP preceding filopodia formation in neuronal growth cones, and uncover a molecular heterogeneity whereby different filopodia display markedly different responses to changes in the accumulation of ENA and VASP fluorescence in their tips over time.

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Systems Biology and Kidney Disease

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.09990819 ◽

2020 ◽

Vol 15 (5) ◽

pp. 695-703 ◽

Cited By ~ 2

Author(s):

Jennifer A. Schaub ◽

Habib Hamidi ◽

Lalita Subramanian ◽

Matthias Kretzler

Keyword(s):

Systems Biology ◽

Molecular Mechanisms ◽

Kidney Diseases ◽

Clinical Care ◽

Treatment Options ◽

Cell Types ◽

Current State ◽

Health And Disease ◽

National Databases ◽

Different Cell Types

The kidney is a complex organ responsible for maintaining multiple aspects of homeostasis in the human body. The combination of distinct, yet interrelated, molecular functions across different cell types make the delineation of factors associated with loss or decline in kidney function challenging. Consequently, there has been a paucity of new diagnostic markers and treatment options becoming available to clinicians and patients in managing kidney diseases. A systems biology approach to understanding the kidney leverages recent advances in computational technology and methods to integrate diverse sets of data. It has the potential to unravel the interplay of multiple genes, proteins, and molecular mechanisms that drive key functions in kidney health and disease. The emergence of large, detailed, multilevel biologic and clinical data from national databases, cohort studies, and trials now provide the critical pieces needed for meaningful application of systems biology approaches in nephrology. The purpose of this review is to provide an overview of the current state in the evolution of the field. Recent successes of systems biology to identify targeted therapies linked to mechanistic biomarkers in the kidney are described to emphasize the relevance to clinical care and the outlook for improving outcomes for patients with kidney diseases.

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Single-cell RNA-Seq Reveals Transcriptional Landscape and Intra-tumor Heterogenicity in Gallbladder Cancer Liver Metastasis Microenvironment

10.21203/rs.3.rs-117830/v1 ◽

2020 ◽

Author(s):

Wenhua You ◽

Xiangyu Li ◽

Peng Wang ◽

Bowen Sha ◽

Yuan Liang ◽

...

Keyword(s):

T Cells ◽

Liver Metastasis ◽

Gallbladder Cancer ◽

Single Cell ◽

Molecular Mechanisms ◽

Cell Types ◽

Malignant Cells ◽

Different Cell Types ◽

High Degree

Abstract Background: Gallbladder cancer (GBC) is a highly aggressive biliary epithelial malignancy. Tumor invasion and metastasis contributed to the high mortality of GBC patients. However, molecular mechanisms involved in GBC metastases are still little known. Methods: We performed single-cell RNA sequencing on GBC liver metastasis tissue and analyzed the data based on different cell types.Results: In this study, 8 cell types, including T cells, B cells, malignant cells, fibroblasts, endothelial cells, macrophages, dendritic cells, and mast cells were identified. Malignant cells displayed a high degree of intra-tumor heterogenicity and neutrophils could promote GBC progression in vitro. Besides, cytotoxic CD8+ T cells became exhausted and CD4+ Tregs presented immunosuppressive characteristics. Macrophages played an important role in the tumor microenvironment. We identified three distinct macrophage subsets and emerged M2 polarization. We also found that cancer-associated fibroblasts exhibited heterogeneity and promoted GBC metastasis. Conclusions: In conclusion, our work provided a landscape view at the single-cell level and may clear the way for the therapy of GBC metastases.

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Cellular and molecular mechanisms that regulate mammalian digit tip regeneration

Open Biology ◽

10.1098/rsob.200194 ◽

2020 ◽

Vol 10 (9) ◽

pp. 200194

Author(s):

Mekayla A. Storer ◽

Freda D. Miller

Keyword(s):

Tissue Regeneration ◽

Molecular Mechanisms ◽

Cell Mass ◽

Cell Types ◽

Original Structure ◽

Mammalian Tissue ◽

Blastema Formation ◽

Different Cell Types ◽

Proliferating Cell ◽

Adult Mammal

Digit tip regeneration is one of the few examples of true multi-tissue regeneration in an adult mammal. The key step in this process is the formation of the blastema, a transient proliferating cell mass that generates the different cell types of the digit to replicate the original structure. Failure to form the blastema results in a lack of regeneration and has been postulated to be the reason why mammalian limbs cannot regrow following amputation. Understanding how the blastema forms and functions will help us to determine what is required for mammalian regeneration to occur and will provide insights into potential therapies for mammalian tissue regeneration and repair. This review summarizes the cellular and molecular mechanisms that influence murine blastema formation and govern digit tip regeneration.

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Wound healing and local neuroendocrine regulation in the injured liver

Expert Reviews in Molecular Medicine ◽

10.1017/s146239940800063x ◽

2008 ◽

Vol 10 ◽

Cited By ~ 11

Author(s):

Mohammad R. Ebrahimkhani ◽

Ahmed M. Elsharkawy ◽

Derek A. Mann

Keyword(s):

Wound Healing ◽

Molecular Mechanisms ◽

Cell Types ◽

Neuroendocrine System ◽

Therapeutic Interventions ◽

Antifibrotic Therapy ◽

Complex Process ◽

Wound Healing Response ◽

Fibrotic Scar ◽

Different Cell Types

The hepatic wound-healing response is a complex process involving many different cell types and factors. It leads to the formation of excessive matrix and a fibrotic scar, which ultimately disrupts proper functioning of the liver and establishes cirrhosis. Activated hepatic myofibroblasts, which are derived from cells such as hepatic stellate cells (HSCs), play a key role in this process. Upon chronic liver injury, there is an upregulation in the local neuroendocrine system and it has recently been demonstrated that activated HSCs express specific receptors and respond to different components of this system. Neuroendocrine factors and their receptors participate in a complex network that modulates liver inflammation and wound healing, and controls the development and progression of liver fibrosis. The first part of this review provides an overview of the molecular mechanisms governing hepatic wound healing. In the second section, we explore important components of the hepatic neuroendocrine system and their recently highlighted roles in HSC biology and hepatic fibrogenesis. We discuss the therapeutic interventions that are being developed for use in antifibrotic therapy.

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Modelling molecular mechanisms of breast cancer and invasion: lessons from the normal gland

Biochemical Society Transactions ◽

10.1042/bst0350018 ◽

2007 ◽

Vol 35 (1) ◽

pp. 18-22 ◽

Cited By ~ 34

Author(s):

M.J. Bissell

Keyword(s):

Breast Cancer ◽

Cell Culture ◽

Molecular Mechanisms ◽

Three Dimensional ◽

Cell Types ◽

Genes And Environment ◽

Different Cell Types ◽

Cancerous Cells ◽

Cancer Studies ◽

Dimensional Cell

The interplay between genes and environment is complex, particularly when it comes to cancer. Studies on breast cancer cells have shown that environmental influences dominate over genotype in their effect on phenotype, and can cause cancerous cells to revert to a non-malignant phenotype, while remaining genotypically malignant. Using breast tissue in three-dimensional cell culture has proved a better model than traditional two-dimensional cell culture in that different cell types can be seen to behave differently to the same pro-apoptotic signal, with normal cells surviving.

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Isolation, sequence, and differential expression of a human K7 gene in simple epithelial cells.

The Journal of Cell Biology ◽

10.1083/jcb.107.4.1337 ◽

1988 ◽

Vol 107 (4) ◽

pp. 1337-1350 ◽

Cited By ~ 30

Author(s):

C Glass ◽

E Fuchs

Keyword(s):

Epithelial Cells ◽

Differential Expression ◽

Molecular Mechanisms ◽

Human Gene ◽

Cell Types ◽

Regulatory Elements ◽

Gene Encoding ◽

Keratin Gene ◽

Base Level ◽

Different Cell Types

Simple epithelial cells synthesize a different set of keratins than epidermal cells. In experiments reported in this manuscript, we show that the base level of keratin expression in simple epithelial cells is variable for different cell types, and that, in some simple epithelia, this level can be upregulated by increasing the exposure of cells to retinoids, but not glucocorticoids or estradiol. To elucidate the molecular mechanisms underlying simple epithelial keratin gene regulation, we have isolated and characterized a human gene encoding the simple epithelial keratin K7. By examining the possible regulatory elements of this gene and by investigating the behavior of this gene introduced transiently into simple epithelial cells, we have uncovered a possible basis for the differential expression of epidermal and simple epithelial keratin genes.

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Vascular Calcification in Chronic Kidney Disease: Diversity in the Vessel Wall

Biomedicines ◽

10.3390/biomedicines9040404 ◽

2021 ◽

Vol 9 (4) ◽

pp. 404

Author(s):

Prabhatchandra Dube ◽

Armelle DeRiso ◽

Mitra Patel ◽

Dhanushya Battepati ◽

Bella Khatib-Shahidi ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Vascular Calcification ◽

Molecular Mechanisms ◽

Cell Types ◽

Complex Process ◽

Cardiovascular Morbidity And Mortality ◽

Depth Analysis ◽

Multiple Cell ◽

Different Cell Types

Vascular calcification (VC) is one of the major causes of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). VC is a complex process expressing similarity to bone metabolism in onset and progression. VC in CKD is promoted by various factors not limited to hyperphosphatemia, Ca/Pi imbalance, uremic toxins, chronic inflammation, oxidative stress, and activation of multiple signaling pathways in different cell types, including vascular smooth muscle cells (VSMCs), macrophages, and endothelial cells. In the current review, we provide an in-depth analysis of the various kinds of VC, the clinical significance and available therapies, significant contributions from multiple cell types, and the associated cellular and molecular mechanisms for the VC process in the setting of CKD. Thus, we seek to highlight the key factors and cell types driving the pathology of VC in CKD in order to assist in the identification of preventative, diagnostic, and therapeutic strategies for patients burdened with this disease.

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The Potential of Hydrogen Sulfide Donors in Treating Cardiovascular Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms22042194 ◽

2021 ◽

Vol 22 (4) ◽

pp. 2194

Author(s):

Yi-Zhen Wang ◽

Ebenezeri Erasto Ngowi ◽

Di Wang ◽

Hui-Wen Qi ◽

Mi-Rong Jing ◽

...

Keyword(s):

Hydrogen Sulfide ◽

Cardiovascular Diseases ◽

Molecular Mechanisms ◽

Heart Function ◽

Cell Types ◽

Special Focus ◽

Protective Effects ◽

Improve Heart Function ◽

Different Cell Types

Hydrogen sulfide (H2S) has long been considered as a toxic gas, but as research progressed, the idea has been updated and it has now been shown to have potent protective effects at reasonable concentrations. H2S is an endogenous gas signaling molecule in mammals and is produced by specific enzymes in different cell types. An increasing number of studies indicate that H2S plays an important role in cardiovascular homeostasis, and in most cases, H2S has been reported to be downregulated in cardiovascular diseases (CVDs). Similarly, in preclinical studies, H2S has been shown to prevent CVDs and improve heart function after heart failure. Recently, many H2S donors have been synthesized and tested in cellular and animal models. Moreover, numerous molecular mechanisms have been proposed to demonstrate the effects of these donors. In this review, we will provide an update on the role of H2S in cardiovascular activities and its involvement in pathological states, with a special focus on the roles of exogenous H2S in cardiac protection.

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