Periodontal cell mechanotransduction

The periodontium is a structurally and functionally complex tissue that facilitates the anchorage of teeth in jaws. The periodontium consists of various cell types including stem cells, fibroblasts and epithelial cells. Cells of the periodontium are constantly exposed to mechanical stresses generated by biological processes such as the chewing motions of teeth, by flows generated by tongue motions and by forces generated by implants. Mechanical stresses modulate the function of cells in the periodontium, and may play a significant role in the development of periodontal disease. Here, we review the literature on the effect of mechanical forces on periodontal cells in health and disease with an emphasis on molecular and cellular mechanisms.

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Cellular Functions of OCT-3/4 Regulated by Ubiquitination in Proliferating Cells

Cancers ◽

10.3390/cancers12030663 ◽

2020 ◽

Vol 12 (3) ◽

pp. 663

Author(s):

Kwang-Hyun Baek ◽

Jihye Choi ◽

Chang-Zhu Pei

Keyword(s):

Stem Cells ◽

Cellular Proliferation ◽

Critical Role ◽

Embryonic Stem ◽

Cell Types ◽

Ubiquitin Proteasome System ◽

Specific Cell ◽

Cellular Mechanisms ◽

Proliferating Cells ◽

Proliferation And Differentiation

Octamer-binding transcription factor 3/4 (OCT-3/4), which is involved in the tumorigenesis of somatic cancers, has diverse functions during cancer development. Overexpression of OCT-3/4 has been detected in various human somatic tumors, indicating that OCT-3/4 activation may contribute to the development and progression of cancers. Stem cells can undergo self-renewal, pluripotency, and reprogramming with the help of at least four transcription factors, OCT-3/4, SRY box-containing gene 2 (SOX2), Krüppel-like factor 4 (KLF4), and c-MYC. Of these, OCT-3/4 plays a critical role in maintenance of undifferentiated state of embryonic stem cells (ESCs) and in production of induced pluripotent stem cells (iPSCs). Stem cells can undergo partitioning through mitosis and separate into specific cell types, three embryonic germ layers: the endoderm, the mesoderm, and the trophectoderm. It has been demonstrated that the stability of OCT-3/4 is mediated by the ubiquitin-proteasome system (UPS), which is one of the key cellular mechanisms for cellular homeostasis. The framework of the mechanism is simple, but the proteolytic machinery is complicated. Ubiquitination promotes protein degradation, and ubiquitination of OCT-3/4 leads to regulation of cellular proliferation and differentiation. Therefore, it is expected that OCT-3/4 may play a key role in proliferation and differentiation of proliferating cells.

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Cells expressing PAX8 are the main source of homeostatic regeneration of adult mouse endometrial epithelium and give rise to serous endometrial carcinoma

Disease Models & Mechanisms ◽

10.1242/dmm.047035 ◽

2020 ◽

Vol 13 (10) ◽

pp. dmm047035

Author(s):

Dah-Jiun Fu ◽

Andrea J. De Micheli ◽

Mallikarjun Bidarimath ◽

Lora H. Ellenson ◽

Benjamin D. Cosgrove ◽

...

Keyword(s):

Stem Cells ◽

Epithelial Cells ◽

Endometrial Carcinoma ◽

Marrow Cell ◽

Cell Types ◽

Lineage Tracing ◽

Cell Of Origin ◽

Mouse Uterus ◽

Endometrial Epithelium

ABSTRACTHumans and mice have cyclical regeneration of the endometrial epithelium. It is expected that such regeneration is ensured by tissue stem cells, but their location and hierarchy remain debatable. A number of recent studies have suggested the presence of stem cells in the mouse endometrial epithelium. At the same time, it has been reported that this tissue can be regenerated by stem cells of stromal/mesenchymal or bone marrow cell origin. Here, we describe a single-cell transcriptomic atlas of the main cell types of the mouse uterus and epithelial subset transcriptome and evaluate the contribution of epithelial cells expressing the transcription factor PAX8 to the homeostatic regeneration and malignant transformation of adult endometrial epithelium. According to lineage tracing, PAX8+ epithelial cells are responsible for long-term maintenance of both luminal and glandular epithelium. Furthermore, multicolor tracing shows that individual glands and contiguous areas of luminal epithelium are formed by clonal cell expansion. Inactivation of the tumor suppressor genes Trp53 and Rb1 in PAX8+ cells, but not in FOXJ1+ cells, leads to the formation of neoplasms with features of serous endometrial carcinoma, one of the most aggressive types of human endometrial malignancies. Taken together, our results show that the progeny of single PAX8+ cells represents the main source of regeneration of the adult endometrial epithelium. They also provide direct experimental genetic evidence for the key roles of the P53 and RB pathways in the pathogenesis of serous endometrial carcinoma and suggest that PAX8+ cells represent the cell of origin of this neoplasm.

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Mechanoactivation of Wnt/β-catenin pathways in health and disease

Emerging Topics in Life Sciences ◽

10.1042/etls20180042 ◽

2018 ◽

Vol 2 (5) ◽

pp. 701-712 ◽

Cited By ~ 3

Author(s):

Christina M. Warboys

Keyword(s):

Cardiovascular Disease ◽

Wnt Pathway ◽

Mechanical Strain ◽

Cell Types ◽

Mechanical Forces ◽

Lymphatic Endothelium ◽

Canonical Pathways ◽

Health And Disease ◽

Multiple Cell ◽

Sense And Respond

Mechanical forces play an important role in regulating tissue development and homeostasis in multiple cell types including bone, joint, epithelial and vascular cells, and are also implicated in the development of diseases, e.g. osteoporosis, cardiovascular disease and osteoarthritis. Defining the mechanisms by which cells sense and respond to mechanical forces therefore has important implications for our understanding of tissue function in health and disease and may lead to the identification of targets for therapeutic intervention. Mechanoactivation of the Wnt signalling pathway was first identified in osteoblasts with a key role for β-catenin demonstrated in loading-induced osteogenesis. Since then, mechanoregulation of the Wnt pathway has also been observed in stem cells, epithelium, chondrocytes and vascular and lymphatic endothelium. Wnt can signal through both canonical and non-canonical pathways, and evidence suggests that both can mediate responses to mechanical strain, stretch and shear stress. This review will discuss our current understanding of the activation of the Wnt pathway in response to mechanical forces.

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Characterization of putative stem cells in isolated human colonic crypt epithelial cells and their interactions with myofibroblasts

AJP Cell Physiology ◽

10.1152/ajpcell.00383.2008 ◽

2009 ◽

Vol 296 (2) ◽

pp. C296-C305 ◽

Cited By ~ 44

Author(s):

S. Samuel ◽

R. Walsh ◽

J. Webb ◽

A. Robins ◽

C. Potten ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Epithelial Cells ◽

Side Population ◽

Cell Types ◽

Population Characteristics ◽

Colonic Crypt ◽

Epithelial Stem Cells ◽

Colonic Crypts ◽

Cell Niche

Colonic epithelial stem cells are believed to be located at the crypt base where they have previously been shown to express musashi-1. The colonic stem cell niche, which includes extracellular matrix and myofibroblasts (together with other cell types), is likely to be important in maintaining the function of the progenitor cells. The aims of our studies were to characterize stem cells in isolated and disaggregated human colonic crypt epithelial cells and investigate their interactions with monolayers of primary human colonic myofibroblasts. In unfractionated preparations of disaggregated colonic crypts, musashi-1 positive cells preferentially adhered to colonic myofibroblasts, despite the presence of excess blocking anti-β1-integrin antibody. These adherent epithelial cells remained viable for a number of days and developed slender processes. Cells with side population characteristics (as demonstrated by ability to expel the dye Hoechst 33342) were consistently seen in the isolated colonic crypt epithelial cells. These side population cells expressed musashi-1, β1-integrin, BerEP4, and CD133. Sorted side population crypt epithelial cells also rapidly adhered to primary colonic myofibroblasts. In conclusion, in preparation of isolated and disaggregated human colonic crypts, cells with stem cell characteristics preferentially adhere to primary human colonic myofibroblasts in a β1-integrin-independent fashion.

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Multiocular organoids from human induced pluripotent stem cells displayed retinal, corneal, and retinal pigment epithelium lineages

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02651-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Helena Isla-Magrané ◽

Anna Veiga ◽

José García-Arumí ◽

Anna Duarri

Keyword(s):

Stem Cells ◽

Retinal Pigment Epithelium ◽

Epithelial Cells ◽

Pluripotent Stem Cells ◽

Eye Development ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Cell Types ◽

Induced Pluripotent ◽

Different Cell Types

Abstract Background Recently, great efforts have been made to design protocols for obtaining ocular cells from human stem cells to model diseases or for regenerative purposes. Current protocols generally focus on isolating retinal cells, retinal pigment epithelium (RPE), or corneal cells and fail to recapitulate the complexity of the tissue during eye development. Here, the generation of more advanced in vitro multiocular organoids from human induced pluripotent stem cells (hiPSCs) is demonstrated. Methods A 2-step method was established to first obtain self-organized multizone ocular progenitor cells (mzOPCs) from 2D hiPSC cultures within three weeks. Then, after the cells were manually isolated and grown in suspension, 3D multiocular organoids were generated to model important cellular features of developing eyes. Results In the 2D culture, self-formed mzOPCs spanned the neuroectoderm, surface ectoderm, neural crest, and RPE, mimicking early stages of eye development. After lifting, mzOPCs developed into different 3D multiocular organoids composed of multiple cell lineages including RPE, retina, and cornea, and interactions between the different cell types and regions of the eye system were observed. Within these organoids, the retinal regions exhibited correct layering and contained all major retinal cell subtypes as well as retinal morphological cues, whereas the corneal regions closely resembled the transparent ocular-surface epithelium and contained of corneal, limbal, and conjunctival epithelial cells. The arrangement of RPE cells also formed organoids composed of polarized pigmented epithelial cells at the surface that were completely filled with collagen matrix. Conclusions This approach clearly demonstrated the advantages of the combined 2D-3D construction tissue model as it provided a more ocular native-like cellular environment than that of previous models. In this complex preparations, multiocular organoids may be used to model the crosstalk between different cell types in eye development and disease. Graphical abstract

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Origin of Myofibroblasts in Lung Fibrosis

Current Tissue Microenvironment Reports ◽

10.1007/s43152-020-00022-9 ◽

2020 ◽

Vol 1 (4) ◽

pp. 155-162

Author(s):

CF Hung

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Epithelial Cells ◽

Lung Fibrosis ◽

Cell Types ◽

Mesenchymal Cells ◽

Lineage Tracing ◽

Alveolar Epithelial Cells ◽

Multiple Sources ◽

Alveolar Epithelial

Abstract Purpose of Review In this brief review, we will highlight important observational and experimental data in the literature that address the origin of scar-forming cells in lung fibrosis. Recent Findings Several cellular sources of activated scar-forming cells (myofibroblasts) have been postulated including alveolar epithelial cells; circulating fibrocytes; and lung stromal cell subpopulations including resident fibroblasts, pericytes, and resident mesenchymal stem cells. Recent advances in lineage-tracing models, however, fail to provide experimental evidence for epithelial and fibrocyte origins of lung myofibroblasts. Resident mesenchymal cells of the lung, which include various cell types including resident fibroblasts, pericytes, and resident mesenchymal stem cells, appear to be important sources of myofibroblasts in murine models of lung injury and fibrosis. Summary Lung myofibroblasts likely originate from multiple sources of lung-resident mesenchymal cells. Their relative contributions may vary depending on the type of injury. Although lineage-tracing experiments have failed to show significant contribution from epithelial cells or fibrocytes, they may play important functional roles in myofibroblast activation through paracrine signaling.

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Predicting Relative Protein Abundance via Sequence-Based Information

10.1101/2021.11.08.467260 ◽

2021 ◽

Author(s):

Gregory Parkes ◽

Rob M Ewing ◽

Mahesan Niranjan

Keyword(s):

Cell Lines ◽

Significant Proportion ◽

Protein Abundance ◽

Mrna Levels ◽

Biological Processes ◽

Cellular Mechanisms ◽

Regulatory Processes ◽

Complex Interactions ◽

Health And Disease ◽

Multiple Cell

Understanding the complex interactions between transcriptome and proteome is essential in uncovering cellular mechanisms both in health and disease contexts. The limited correlations between corresponding transcript and protein abundance suggest that regulatory processes tightly govern information flow surrounding transcription and translation, and beyond. In this study we adopt an approach which expands the feature scope that models the human proteome: we develop machine learning models that incorporate sequence-derived features (SDFs), sometimes in conjunction with corresponding mRNA levels. We develop a large resource of sequence-derived features which cover a significant proportion of the H. sapiens proteome, demonstrate which of these features are significant in prediction on multiple cell lines, and suggest insights into which biological processes can be explained using these features. We reveal that (a) SDFs are significantly better at protein abundance prediction across multiple cell lines both in steady-state and dynamic contexts, (b) that SDFs can cover the domain of translation with relative efficiency but struggle with cell-line specific pathways and (c) provide a resource which can be plugged into many subsequent protein-centric analyses.

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T helper cells modulate intestinal stem cell renewal and differentiation

10.1101/217133 ◽

2017 ◽

Cited By ~ 2

Author(s):

Moshe Biton ◽

Adam L. Haber ◽

Semir Beyaz ◽

Noga Rogel ◽

Christopher Smillie ◽

...

Keyword(s):

Stem Cells ◽

T Cells ◽

Epithelial Cells ◽

Immune Cell ◽

Intestinal Epithelial Cells ◽

Cell Types ◽

Intestinal Epithelial ◽

T Helper ◽

Self Renewal

AbstractIn the small intestine, a cellular niche of diverse accessory cell types supports the rapid generation of mature epithelial cell types through self-renewal, proliferation, and differentiation of intestinal stem cells (ISCs). However, not much is known about interactions between immune cells and ISCs, and it is unclear if and how immune cell dynamics affect eventual ISC fate or the balance between self-renewal and differentiation. Here, we used single-cell RNA-seq (scRNA-Seq) of intestinal epithelial cells (IECs) to identify new mechanisms for ISC–immune cell interactions. Surprisingly, MHC class II (MHCII) is enriched in two distinct subsets of Lgr5+ crypt base columnar ISCs, which are also distinguished by higher proliferation rates. Using co-culture of T cells with intestinal organoids, cytokine stimulations, and in vivo mouse models, we confirm that CD4+ T helper (Th) cells communicate with ISCs and affect their differentiation, in a manner specific to the Th subtypes and their signature cytokines and dependent on MHCII expression by ISCs. Specific inducible knockout of MHCII in intestinal epithelial cells in mice in vivo results in expansion of the ISC pool. Mice lacking T cells have expanded ISC pools, whereas specific depletion of Treg cells in vivo results in substantial reduction of ISC numbers. Our findings show that interactions between Th cells and ISCs mediated via MHCII expressed in intestinal epithelial stem cells help orchestrate tissue-wide responses to external signals.

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The Mechanoadaptation Concept of Cells

Stem Cells and Regenerative Medicine - Biomedical and Health Research ◽

10.3233/bhr210010 ◽

2021 ◽

Author(s):

J.F. Stoltz ◽

Y. Remond ◽

D. George ◽

J. Magdalou ◽

Y.P. Li ◽

...

Keyword(s):

Stem Cells ◽

Shear Stress ◽

Bone Cells ◽

Biological Effects ◽

Mechanical Stresses ◽

Functional Adaptation ◽

Mechanical Forces ◽

Tissue Remodelling ◽

Hip Cartilage ◽

Almost All

Almost all cells in the human body are subjected to mechanical stresses. These forces can vary from a few Pascals (shear stress) to some mega Pascals (on hip cartilage). It is now well known that mechanical forces have a decisive effect on cellular physiology. In 1880, W. Roux introduced the concept of functional adaptation; which can be defined as a quantitative autoregulation controlled by stimuli like mechanical forces. These stresses influence functionality and cellular metabolism and can lead to appropriate tissue remodelling by triggering a cascade of reactions (mechanotransduction), being the signal for the adaptation of cells and tissues. However, although the main biological effects of mechanical forces are well documented, the relation between mechanical forces and physiological phenomena is largely unknown. In this paper, some effects of mechanical stresses on different cells (mesenchymal stem cells, bone cells, chondrocyte, endothelial cells, vascular or muscular cells, etc.) are summarized.

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