scholarly journals Single cell transcriptomic analysis reveals cellular diversity of murine esophageal epithelium and age-associated mitochondrial dysfunction

2021 ◽  
Author(s):  
Mohammad Faujul Kabir ◽  
Adam Karami ◽  
Ricardo Cruz-Acuna ◽  
Alena Klochkova ◽  
Reshu Saxena ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Single Cell ◽  
Molecular Characteristics ◽  
Molecular Heterogeneity ◽  
Basal Cells ◽  
Esophageal Epithelium ◽  
Squamous Differentiation ◽  
Cell Clusters ◽  
Tissue Aging ◽  
The Impact

ABSTRACTStratified squamous epithelium of the esophagus is comprised of basal keratinocytes that execute a terminal differentiation program in overlying suprabasal and superficial cell layers. Although morphologic progression coupled with expression of specific molecular markers has been characterized along the esophageal epithelial differentiation gradient, the molecular heterogeneity within the cell types along this trajectory has yet to be classified at the level of single cell resolution. To explore the molecular characteristics of esophageal keratinocytes along the squamous differentiation continuum, we performed single cell RNA-Sequencing transcriptomic profiling of 7,972 cells from murine esophageal epithelial sheets. We identified 8 distinct cell clusters in esophageal epithelium, unveiling an unexpected level of diversity, particularly among basal cells. We further mapped the cellular pathways and lineage trajectories within basal, suprabasal, and superficial clusters as well as within the heterogeneous basal cell populations, providing a comprehensive molecular view of esophageal epithelial cells in the context of squamous differentiation. Finally, we explored the impact of tissue aging upon esophageal epithelial cell clusters and demonstrated that mitochondrial dysfunction is a feature of aging in normal esophageal epithelium. These studies provide an unparalleled molecular perspective on murine esophageal keratinocytes that will serve as a valuable resource for dissecting cell type-specific roles in esophageal biology under conditions of homeostasis, aging, and tissue pathology.

scholarly journals Single-Cell Transcriptomic Landscape Reveals the Differences in Cell Differentiation and Immune Microenvironment of Papillary Thyroid Carcinoma Between Genders

2020 ◽  
Author(s):  
Miaoguan Peng ◽  
Guohong Wei ◽  
Yunjian Zhang ◽  
Hai Li ◽  
Yingrong Lai ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cells ◽  
Thyroid Carcinoma ◽  
Single Cell ◽  
Dominant Gene ◽  
Immune Microenvironment ◽  
Male And Female ◽  
Cell Clusters ◽  
Female Patients ◽  
The Impact

Abstract BackgroundPapillary thyroid carcinoma (PTC) is the main pathological type of thyroid carcinoma (TC). Gender is a prominent background parameter for patients with PTC. Here, we aimed to delineate the differences in cell clusters and immune microenvironment in relation to gender in PTC.ResultsMalignant epithelial cells were divided into two distinct subsets in male and female patients with PTC. Moreover, significant differences involving copy-number variations (CNVs), gene profiles, and cell differentiation were detected between male and female patients. Regarding the interactions of fibroblasts and endothelial cells with malignant epithelial cells, members of the human leukocyte antigen (HLA) family and their receptors were considered as typical in female patients with PTC, while transforming growth factor beta 1 (TGFB1) and its receptors were typical of male patients with PTC. The characteristics of B cells, including cell clusters, cell differentiation, and dominant gene sets, were significantly different between genders. ConclusionsOur data revealed the detailed differences in cell clusters and immune microenvironment in PTC according to gender at the single-cell level, which provided new insights into the understanding of the impact of gender on PTC.

scholarly journals The Impact of Single-Cell Genomics on Adipose Tissue Research

2020 ◽  
Vol 21 (13) ◽  
pp. 4773
Author(s):  
Alana Deutsch ◽  
Daorong Feng ◽  
Jeffrey E. Pessin ◽  
Kosaku Shinoda
Keyword(s):  
Adipose Tissue ◽  
Single Cell ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Diabetes Research ◽  
Obesity And Diabetes ◽  
Important Regulator ◽  
Whole Body Metabolism ◽  
Tissue Aging ◽  
The Impact

Adipose tissue is an important regulator of whole-body metabolism and energy homeostasis. The unprecedented growth of obesity and metabolic disease worldwide has required paralleled advancements in research on this dynamic endocrine organ system. Single-cell RNA sequencing (scRNA-seq), a highly meticulous methodology used to dissect tissue heterogeneity through the transcriptional characterization of individual cells, is responsible for facilitating critical advancements in this area. The unique investigative capabilities achieved by the combination of nanotechnology, molecular biology, and informatics are expanding our understanding of adipose tissue’s composition and compartmentalized functional specialization, which underlie physiologic and pathogenic states, including adaptive thermogenesis, adipose tissue aging, and obesity. In this review, we will summarize the use of scRNA-seq and single-nuclei RNA-seq (snRNA-seq) in adipocyte biology and their applications to obesity and diabetes research in the hopes of increasing awareness of the capabilities of this technology and acting as a catalyst for its expanded use in further investigation.

Single Cell Molecular Genotyping Reveals Significant Molecular Heterogeneity at Diagnosis and Emergence of Clonal Dominance at Relapse

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2944-2944
Author(s):  
Rong Zeng ◽  
Soheil Meshinchi
Keyword(s):  
Single Cell ◽  
Single Cells ◽  
Uniparental Disomy ◽  
Leukemic Cells ◽  
Molecular Characteristics ◽  
Signal Recovery ◽  
Molecular Heterogeneity ◽  
Wild Type ◽  
Molecular Genotyping ◽  
A Minor

Abstract Acute myeloid leukemia is a heterogeneous disease with significant variation in morphologic, cytogenetic, and molecular characteristics. We used single cell molecular genotyping to investigate the extent of molecular heterogeneity in individual patients with FLT3/ITD, WT1 and c-KIT mutations. Diagnostic leukemic samples from patients with FLT3/ITD (N=10) with varying FLT3/ITD allelic ratios (proportion of mutant to wild type product, ITD-AR) were flow sorted to immunophenotypic homogeneity (CD45dim/CD34+/CD33+) and individual leukemic blasts were isolated and directly genotyped. Single cell signal recovery as evident by the detection of FLT3 signal ranged from 39% to 88% (median 58%). Single cells from FLT3/ITD-positive samples demonstrated significant molecular heterogeneity with the presence of 3 distinct FLT3 genotypes: heterozygous FLT3/ITD, homozygous FLT3/ITD and wild type FLT3 (FLT3/WT). Proportion of cells with homozygous FLT3/ITD varied from 3% to 80% and directly correlated with the diagnostic ITD-AR, where those with high allelic ratios had a higher proportion of homozygous ITD cells and in those with the highest ITD-AR, with demonstrated 13q uniparental disomy (13q UPD), cells with homozygous ITD were the dominant clone. We further evaluated relapse specimens from 3 patients with FLT3/ITD, where cells with homozygous ITD was a minor clone at diagnosis (15%–30%). Single cell FLT3 genotyping of these specimens revealed significant expansion and clonal dominance of the homozygous ITD at relapse, where >85% of leukemic cells harbored homozygous ITD (and presumed 13q UPD). We demonstrated similar molecular heterogeneity in patients with WT1 and c-KIT mutations, with detection of homozygous mutations in 20–60% of the cells tested. Single cell genotyoing demonstrates significant molecular heterogeneity in AML that may not be evident by conventional methods. This data provides direct evidence that cells with homozygous FLT3/ITD and associated 13q UPD may be present as a minor population at the time of diagnosis and emerge as the dominant clone at relapse. Such a molecular heterogeneity and emergence of clonal dominance by an individual clone may provide insight into mechanism of disease resistance. Extent of molecular heterogeneity may also be important in our interpretation of data obtained from biologic specimens.

The Impact of Translational Research in Breast Cancer Care: Can we Improve the Therapeutic Scenario?

2018 ◽  
Vol 18 (6) ◽  
pp. 832-836
Author(s):  
Giuseppe Buono ◽  
Francesco Schettini ◽  
Francesco Perri ◽  
Grazia Arpino ◽  
Roberto Bianco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Translational Research ◽  
Cell Biology ◽  
Cancer Biology ◽  
Hormone Receptors ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Molecular Heterogeneity ◽  
Therapeutic Implications ◽  
The Impact

Traditionally, breast cancer (BC) is divided into different subtypes defined by immunohistochemistry (IHC) according to the expression of hormone receptors and overexpression/amplification of human epidermal growth factor receptor 2 (HER2), with crucial therapeutic implications. In the last few years, the definition of different BC molecular subgroups within the IHC-defined subtypes and the identification of the important role that molecular heterogeneity can play in tumor progression and treatment resistance have inspired the search for personalized therapeutic approaches. In this scenario, translational research represents a key strategy to apply knowledge from cancer biology to the clinical setting, through the study of all the tumors “omics”, including genomics, transcriptomics, proteomics, epigenomics, and metabolomics. Importantly, the introduction of new high-throughput technologies, such as next generation sequencing (NGS) for the study of cancer genome and transcriptome, greatly amplifies the potential and the applications of translational research in the oncology field. Moreover, the introduction of new experimental approaches, such as liquid biopsy, as well as new-concept clinical trials, such as biomarker-driven adaptive studies, may represent a turning point for BC translational research. </P><P> It is likely that translational research will have in the near future a significant impact on BC care, especially by giving us the possibility to dissect the complexity of tumor cell biology and develop new personalized treatment strategies.

scholarly journals Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update

2021 ◽  
Vol 22 (9) ◽  
pp. 4646
Author(s):  
Alexey A. Tinkov ◽  
Monica M. B. Paoliello ◽  
Aksana N. Mazilina ◽  
Anatoly V. Skalny ◽  
Airton C. Martins ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Mitochondrial Dysfunction ◽  
Synaptic Dysfunction ◽  
Future Research ◽  
Protective Mechanism ◽  
Autophagic Flux ◽  
Future Research Directions ◽  
The Impact

Understanding of the immediate mechanisms of Mn-induced neurotoxicity is rapidly evolving. We seek to provide a summary of recent findings in the field, with an emphasis to clarify existing gaps and future research directions. We provide, here, a brief review of pertinent discoveries related to Mn-induced neurotoxicity research from the last five years. Significant progress was achieved in understanding the role of Mn transporters, such as SLC39A14, SLC39A8, and SLC30A10, in the regulation of systemic and brain manganese handling. Genetic analysis identified multiple metabolic pathways that could be considered as Mn neurotoxicity targets, including oxidative stress, endoplasmic reticulum stress, apoptosis, neuroinflammation, cell signaling pathways, and interference with neurotransmitter metabolism, to name a few. Recent findings have also demonstrated the impact of Mn exposure on transcriptional regulation of these pathways. There is a significant role of autophagy as a protective mechanism against cytotoxic Mn neurotoxicity, yet also a role for Mn to induce autophagic flux itself and autophagic dysfunction under conditions of decreased Mn bioavailability. This ambivalent role may be at the crossroad of mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis. Yet very recent evidence suggests Mn can have toxic impacts below the no observed adverse effect of Mn-induced mitochondrial dysfunction. The impact of Mn exposure on supramolecular complexes SNARE and NLRP3 inflammasome greatly contributes to Mn-induced synaptic dysfunction and neuroinflammation, respectively. The aforementioned effects might be at least partially mediated by the impact of Mn on α-synuclein accumulation. In addition to Mn-induced synaptic dysfunction, impaired neurotransmission is shown to be mediated by the effects of Mn on neurotransmitter systems and their complex interplay. Although multiple novel mechanisms have been highlighted, additional studies are required to identify the critical targets of Mn-induced neurotoxicity.

scholarly journals Morphodynamic signatures of MDA-MB-231 single cells and cell doublets undergoing invasion in confined microenvironments

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xingjian Zhang ◽  
Trevor Chan ◽  
Michael Mak
Keyword(s):  
Single Cell ◽  
Single Cells ◽  
Leading Edge ◽  
Cell Group ◽  
Collective State ◽  
Long Term Effects ◽  
Cell Metastasis ◽  
Geometric Confinement ◽  
Short And Long Term ◽  
The Impact

AbstractCancer cell metastasis is a major factor in cancer-related mortality. During the process of metastasis, cancer cells exhibit migratory phenotypes and invade through pores in the dense extracellular matrix. However, the characterization of morphological and subcellular features of cells in similar migratory phenotypes and the effects of geometric confinement on cell morphodynamics are not well understood. Here, we investigate the phenotypes of highly aggressive MDA-MB-231 cells in single cell and cell doublet (an initial and simplified collective state) forms in confined microenvironments. We group phenotypically similar single cells and cell doublets and characterize related morphological and subcellular features. We further detect two distinct migratory phenotypes, fluctuating and non-fluctuating, within the fast migrating single cell group. In addition, we demonstrate an increase in the number of protrusions formed at the leading edge of cells after invasion through geometric confinement. Finally, we track the short and long term effects of varied degrees of confinement on protrusion formation. Overall, our findings elucidate the underlying morphological and subcellular features associated with different single cell and cell doublet phenotypes and the impact of invasion through confined geometry on cell behavior.

scholarly journals Ultrasound-assisted extraction of protein from Bombay locusts and its impact on functional and antioxidative properties

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Passakorn Kingwascharapong ◽  
Manat Chaijan ◽  
Supatra Karnjanapratum
Keyword(s):  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Surface Hydrophobicity ◽  
Molecular Characteristics ◽  
Ultrasound Assisted Extraction ◽  
Antioxidative Properties ◽  
Assisted Extraction ◽  
Ultrasound Assisted ◽  
Nonessential Amino Acids ◽  
The Impact

AbstractImpact of ultrasound-assisted process (UAP) on yield, functional properties, antioxidant properties and molecular characteristics of protein extracted from Bombay locusts (BL) (Patanga succinta L.) was studied. Different conditions of UAP were implemented for different amplitudes (40–60%) and times (10–30 min) during aqueous extraction. Notably, UAP could enhance yield and protein recovery, compared with those from typical process (TP) (continuously stirred at 100 rpm at room temperature for 1 h). UAP conditions used governed the change of surface hydrophobicity and free α-amino content of BL. UAP could improve solubility of BL, especially at pH levels higher than 2. UAP had no significant (p > 0.05) detrimental effects on foaming capacity and stability of BL. Nevertheless, UAP, particularly at 50–60% amplitudes, affected the emulsion activity and stability of BL. UAP provided BL with high radical scavenging activities and good electron donating ability, especially that from 60% amplitude for 20 min (UAP-60/20). UAP-60/20 showed the impact on change of isoelectric point and molecular characteristic monitored by Fourier transform infrared (FTIR) of BL, compared to those from TP. In addition, BL was also an excellent source of both essential and nonessential amino acids. Therefore, UAP potentially enhanced BL extraction efficiency, resulting the BL with good functional and antioxidative properties.

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