-Related Dilated Cardiomyopathy: Single-Cell Transcriptomics during Patient-Derived iPSC Differentiation Support Cell Type and Lineage-Specific Dysregulation of Gene Expression and Development for Cardiomyocytes and Epicardium-Derived Cells with Lamin A/C Haploinsufficiency.

-related dilated cardiomyopathy (DCM) is an autosomal-dominant genetic condition with cardiomyocyte and conduction system dysfunction often resulting in heart failure or sudden death. The condition is caused by mutation in the Lamin A/C () gene encoding Type-A nuclear lamin proteins involved in nuclear integrity, epigenetic regulation of gene expression, and differentiation. The molecular mechanisms of the disease are not completely understood, and there are no definitive treatments to reverse progression or prevent mortality.

Polyunsaturated Fatty Acid - mediated Cellular Rejuvenation for Reversing Age-related Vision Decline.

The retina is uniquely enriched in polyunsaturated fatty acids (PUFAs), which are primarily localized in cell membranes, where they govern membrane biophysical properties such as diffusion, permeability, domain formation, and curvature generation. During aging, alterations in lipid metabolism lead to reduced content of very long-chain PUFAs (VLC-PUFAs) in the retina, and this decline is associated with normal age-related visual decline and pathological age-related macular degeneration (AMD). (Elongation of very-long-chain fatty acids-like 2) encodes a transmembrane protein that produces precursors to docosahexaenoic acid (DHA) and VLC-PUFAs, and methylation level of its promoter is currently the best predictor of chronological age.

Sequential emergence and contraction of epithelial subtypes in the prenatal human choroid plexus revealed by a stem cell model.

Despite the major roles of choroid plexus epithelial cells (CPECs) in brain homeostasis and repair, their developmental lineage and diversity remain undefined. In simplified differentiations from human pluripotent stem cells, derived CPECs (dCPECs) displayed canonical properties and dynamic multiciliated phenotypes that interacted with Aβ uptake. Single dCPEC transcriptomes over time correlated well with human organoid and fetal CPECs, while pseudotemporal and cell cycle analyses highlighted the direct CPEC origin from neuroepithelial cells.

O-GlcNAcase regulates pluripotency states of human embryonic stem cells.

Understanding the regulation of human embryonic stem cells (hESCs) pluripotency is critical to advance the field of developmental biology and regenerative medicine. Despite the recent progress, molecular events regulating hESC pluripotency, especially the transition between naive and primed states, still remain unclear. Here we show that naive hESCs display lower levels of O-linked N-acetylglucosamine (O-GlcNAcylation) than primed hESCs.

-Related Dilated Cardiomyopathy: Single-Cell Transcriptomics during Patient-derived iPSC Differentiation Support Cell type and Lineage-specific Dysregulation of Gene Expression and Development for Cardiomyocytes and Epicardium-Derived Cells with Lamin A/C Haploinsufficiency.

-Related Dilated Cardiomyopathy (DCM) is an autosomal-dominant genetic condition with cardiomyocyte and conduction system dysfunction often resulting in heart failure or sudden death. The condition is caused by mutation in the Lamin A/C ( ) gene encoding Type-A nuclear lamin proteins involved in nuclear integrity, epigenetic regulation of gene expression, and differentiation. Molecular mechanisms of disease are not completely understood, and there are no definitive treatments to reverse progression or prevent mortality.

Reconstructing growth and dynamic trajectories from single-cell transcriptomics data.

Time-series single-cell RNA sequencing (scRNA-seq) datasets provide unprecedented opportunities to learn dynamic processes of cellular systems. Due to the destructive nature of sequencing, it remains challenging to link the scRNA-seq snapshots sampled at different time points. Here we present TIGON, a dynamic, unbalanced optimal transport algorithm that reconstructs dynamic trajectories and population growth simultaneously as well as the underlying gene regulatory network from multiple snapshots.

EdeepSADPr: an extensive deep-learning architecture for prediction of the crosstalks of serine phosphorylation and ADP-ribosylation.

The post-translational modification (PTM) crosstalk refers to the interactions between different types of PTMs that occur on the same residue site of a protein. The crosstalk sites generally have different characteristics from those with the single PTM type. Studies targeting the latter's features have been widely conducted, while studies on the former's characteristics are rare.

Single-cell analysis of human basal cell carcinoma reveals novel regulators of tumor growth and the tumor microenvironment.

How basal cell carcinoma (BCC) interacts with its tumor microenvironment to promote growth is unclear. We use singe-cell RNA sequencing to define the human BCC ecosystem and discriminate between normal and malignant epithelial cells. We identify spatial biomarkers of tumors and their surrounding stroma that reinforce the heterogeneity of each tissue type.

A Study of Gene Expression, Structure, and Contractility of iPSC-Derived Cardiac Myocytes from a Family with Heart Disease due to LMNA Mutation.

Genetic mutations to the Lamin A/C gene (LMNA) can cause heart disease, but the mechanisms making cardiac tissues uniquely vulnerable to the mutations remain largely unknown. Further, patients with LMNA mutations have highly variable presentation of heart disease progression and type. In vitro patient-specific experiments could provide a powerful platform for studying this phenomenon, but the use of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) introduces heterogeneity in maturity and function thus complicating the interpretation of the results of any single experiment.

DeepSADPr: A hybrid-learning architecture for serine ADP-ribosylation site prediction.

Protein adenosine diphosphate-ribosylation (ADPr) is caused by the covalent binding of one or more ADP-ribose moieties to a target protein and regulates the biological functions of the target protein. To fully understand the regulatory mechanism of ADP-ribosylation, the essential step is the identification of the ADPr sites from the proteome. As the experimental approaches are costly and time-consuming, it is necessary to develop a computational tool to predict ADPr sites.

Inference of Intercellular Communications and Multilayer Gene-Regulations of Epithelial-Mesenchymal Transition From Single-Cell Transcriptomic Data.

Epithelial-to-mesenchymal transition (EMT) plays an important role in many biological processes during development and cancer. The advent of single-cell transcriptome sequencing techniques allows the dissection of dynamical details underlying EMT with unprecedented resolution. Despite several single-cell data analysis on EMT, how cell communicates and regulates dynamics along the EMT trajectory remains elusive.

Inference and multiscale model of epithelial-to-mesenchymal transition via single-cell transcriptomic data.

Rapid growth of single-cell transcriptomic data provides unprecedented opportunities for close scrutinizing of dynamical cellular processes. Through investigating epithelial-to-mesenchymal transition (EMT), we develop an integrative tool that combines unsupervised learning of single-cell transcriptomic data and multiscale mathematical modeling to analyze transitions during cell fate decision. Our approach allows identification of individual cells making transition between all cell states, and inference of genes that drive transitions.

Intermediate cell states in epithelial-to-mesenchymal transition.

The transition of epithelial cells into a mesenchymal state (epithelial-to-mesenchymal transition or EMT) is a highly dynamic process implicated in various biological processes. During EMT, cells do not necessarily exist in 'pure' epithelial or mesenchymal states. There are cells with mixed (or hybrid) features of the two, which are termed as the intermediate cell states (ICSs).