scholarly journals A High Content Imaging-Based Approach for Classifying Cellular Phenotypes

2013 ◽  
pp. 41-48 ◽  
Author(s):  
Joseph J. Kim ◽  
Sebastián L. Vega ◽  
Prabhas V. Moghe
Keyword(s):  
High Content Imaging ◽  
Cellular Phenotypes

scholarly journals Mitochondrial Phenotypes Distinguish Pathogenic MFN2 Mutations by Pooled Functional Genomics Screen

2021 ◽  
Author(s):  
Alex L Yenkin ◽  
John C Bramley ◽  
Jason E Waligorski ◽  
Colin L Kremitzki ◽  
Mariel J Liebeskind ◽  
...  
Keyword(s):  
Machine Learning ◽  
Genetic Variation ◽  
Functional Genomics ◽  
Point Mutations ◽  
Human Genetic Variation ◽  
Cellular Phenotype ◽  
High Content Imaging ◽  
Biologically Relevant ◽  
Uncertain Significance ◽  
Cellular Phenotypes

Most human genetic variation is classified as VUS - variants of uncertain significance. While advances in genome editing have allowed innovation in pooled screening platforms, many screens deal with relatively simple readouts (viability, fluorescence) and cannot identify the complex cellular phenotypes that underlie most human diseases. In this paper, we present a generalizable functional genomics platform that combines high-content imaging, machine learning, and microraft isolation in a new method termed "Raft-Seq". We highlight the efficacy of our platform by showing its ability to distinguish pathogenic point mutations of the mitochondrial regulator MFN2, even when the cellular phenotype is subtle. We also show that our platform achieves its efficacy using multiple cellular features, which can be configured on-the-fly. Raft-Seq enables a new way to perform pooled screening on sets of mutations in biologically relevant cells, with the ability to physically capture any cell with a perturbed phenotype and expand it clonally, directly from the primary screen.

scholarly journals Methyltransferase like 13 mediates the translation of Snail in head and neck squamous cell carcinoma

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Xiaochen Wang ◽  
Kang Li ◽  
Yuehan Wan ◽  
Fangfang Chen ◽  
Maosheng Cheng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Translation Efficiency ◽  
Mechanism Study ◽  
Clinical Prognosis ◽  
Cellular Phenotypes

AbstractMethyltransferase like 13 (METTL13), a kind of methyltransferase, is implicated in protein binding and synthesis. The upregulation of METTL13 has been reported in a variety of tumors. However, little was known about its potential function in head and neck squamous cell carcinoma (HNSCC) so far. In this study, we found that METTL13 was significantly upregulated in HNSCC at both mRNA and protein level. Increased METTL13 was negatively associated with clinical prognosis. And METTL13 markedly affected HNSCC cellular phenotypes in vivo and vitro. Further mechanism study revealed that METTL13 could regulate EMT signaling pathway by mediating enhancing translation efficiency of Snail, the key transcription factor in EMT, hence regulating the progression of EMT. Furthermore, Snail was verified to mediate METTL13-induced HNSCC cell malignant phenotypes. Altogether, our study had revealed the oncogenic role of METTL13 in HNSCC, and provided a potential therapeutic strategy.

scholarly journals Exon Shuffling Played a Decisive Role in the Evolution of the Genetic Toolkit for the Multicellular Body Plan of Metazoa

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 382
Author(s):  
Laszlo Patthy
Keyword(s):  
Transcription Factor ◽  
Decisive Role ◽  
Cell Types ◽  
Body Plan ◽  
Exon Shuffling ◽  
Body Parts ◽  
Multidomain Proteins ◽  
Cellular Phenotypes ◽  
Cell Matrix Interactions ◽  
Genetic Toolkit

Division of labor and establishment of the spatial pattern of different cell types of multicellular organisms require cell type-specific transcription factor modules that control cellular phenotypes and proteins that mediate the interactions of cells with other cells. Recent studies indicate that, although constituent protein domains of numerous components of the genetic toolkit of the multicellular body plan of Metazoa were present in the unicellular ancestor of animals, the repertoire of multidomain proteins that are indispensable for the arrangement of distinct body parts in a reproducible manner evolved only in Metazoa. We have shown that the majority of the multidomain proteins involved in cell–cell and cell–matrix interactions of Metazoa have been assembled by exon shuffling, but there is no evidence for a similar role of exon shuffling in the evolution of proteins of metazoan transcription factor modules. A possible explanation for this difference in the intracellular and intercellular toolkits is that evolution of the transcription factor modules preceded the burst of exon shuffling that led to the creation of the proteins controlling spatial patterning in Metazoa. This explanation is in harmony with the temporal-to-spatial transition hypothesis of multicellularity that proposes that cell differentiation may have predated spatial segregation of cell types in animal ancestors.

scholarly journals Role of SHH in Patterning Human Pluripotent Cells towards Ventral Forebrain Fates

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 914
Author(s):  
Melanie V. Brady ◽  
Flora M. Vaccarino
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Human Development ◽  
Disease Modeling ◽  
Model Systems ◽  
Advantages And Disadvantages ◽  
Technical Ability ◽  
Cellular Phenotypes

The complexities of human neurodevelopment have historically been challenging to decipher but continue to be of great interest in the contexts of healthy neurobiology and disease. The classic animal models and monolayer in vitro systems have limited the types of questions scientists can strive to answer in addition to the technical ability to answer them. However, the tridimensional human stem cell-derived organoid system provides the unique opportunity to model human development and mimic the diverse cellular composition of human organs. This strategy is adaptable and malleable, and these neural organoids possess the morphogenic sensitivity to be patterned in various ways to generate the different regions of the human brain. Furthermore, recapitulating human development provides a platform for disease modeling. One master regulator of human neurodevelopment in many regions of the human brain is sonic hedgehog (SHH), whose expression gradient and pathway activation are responsible for conferring ventral identity and shaping cellular phenotypes throughout the neural axis. This review first discusses the benefits, challenges, and limitations of using organoids for studying human neurodevelopment and disease, comparing advantages and disadvantages with other in vivo and in vitro model systems. Next, we explore the range of control that SHH exhibits on human neurodevelopment, and the application of SHH to various stem cell methodologies, including organoids, to expand our understanding of human development and disease. We outline how this strategy will eventually bring us much closer to uncovering the intricacies of human neurodevelopment and biology.

scholarly journals DNA Methylation of Fibroblast Phenotypes and Contributions to Lung Fibrosis

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1977
Author(s):  
Poojitha Rajasekar ◽  
Jamie Patel ◽  
Rachel L. Clifford
Keyword(s):  
Dna Methylation ◽  
Lung Disease ◽  
Primary Source ◽  
Lung Fibroblast ◽  
Bioactive Molecules ◽  
Lung Fibroblasts ◽  
Covalent Attachment ◽  
Immune Functions ◽  
Cellular Origin ◽  
Cellular Phenotypes

Fibroblasts are an integral part of connective tissue and play a crucial role in developing and modulating the structural framework of tissues by acting as the primary source of extracellular matrix (ECM). A precise definition of the fibroblast remains elusive. Lung fibroblasts orchestrate the assembly and turnover of ECM to facilitate gas exchange alongside performing immune functions including the secretion of bioactive molecules and antigen presentation. DNA methylation is the covalent attachment of a methyl group to primarily cytosines within DNA. DNA methylation contributes to diverse cellular phenotypes from the same underlying genetic sequence, with DNA methylation profiles providing a memory of cellular origin. The lung fibroblast population is increasingly viewed as heterogeneous with between 6 and 11 mesenchymal populations identified across health and lung disease to date. DNA methylation has been associated with different lung fibroblast populations in health and with alterations in lung disease, but to varying extents. In this review, we will discuss lung fibroblast heterogeneity and the evidence for a contribution from DNA methylation to defining cell populations and alterations in disease.

scholarly journals SMRT compounds abrogate cellular phenotypes of ataxia telangiectasia in neural derivatives of patient-specific hiPSCs

2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Peiyee Lee ◽  
Nathan T. Martin ◽  
Kotoka Nakamura ◽  
Soheila Azghadi ◽  
Mandana Amiri ◽  
...  
Keyword(s):  
Ataxia Telangiectasia ◽  
Patient Specific ◽  
Cellular Phenotypes ◽  
Derivatives Of

scholarly journals Valosin-Containing Protein Gene Mutations: Cellular Phenotypes Relevant to Neurodegeneration

2011 ◽  
Vol 44 (2) ◽  
pp. 91-102 ◽  
Author(s):  
Karen S. Poksay ◽  
David T. Madden ◽  
Anna K. Peter ◽  
Kayvan Niazi ◽  
Surita Banwait ◽  
...  
Keyword(s):  
Protein Gene ◽  
Gene Mutations ◽  
Cellular Phenotypes
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