Single-cell transcriptomics of Treg reveals hallmarks and trajectories of immunological aging.

Age-related immunosenescence is characterized by progressive dysfunction of adaptive immune response and increased autoimmunity. Nevertheless, the impact of aging on CD4+ regulatory T cells that are master regulators of the immune system remains largely unclear. Here, we report cellular and molecular hallmarks of regulatory T cells derived from murine lymphoid and adipose tissues at 3, 18, and 24 mo of age, respectively, by analyzing their heterogeneity that displays dynamic changes in transcriptomic effector signatures at a single-cell resolution.

Endogenous Plasmids and Chromosomal Genome Reduction in the Endosymbiont of .

bacteria are well known as endosymbionts that infect a wide range of arthropods and can manipulate host reproduction to promote their vertical transmission. As intracellular bacteria, species undergo dramatic genome evolution, especially their chromosomal genome reduction. Although plasmids have been reported to harbor important genes, the role of these plasmids in the genome evolution is yet to be fully understood.

Comparative Genomics Reveals Insights into the Divergent Evolution of Astigmatic Mites and Household Pest Adaptations.

Highly diversified astigmatic mites comprise many medically important human household pests such as house dust mites causing ∼1-2% of all allergic diseases globally; however, their evolutionary origin and diverse lifestyles including reversible parasitism have not been illustrated at the genomic level, which hampers allergy prevention and our exploration of these household pests. Using six high-quality assembled and annotated genomes, this study not only refuted the monophyly of mites and ticks, but also thoroughly explored the divergence of Acariformes and the diversification of astigmatic mites. In monophyletic Acariformes, Prostigmata known as notorious plant pests first evolved, and then rapidly evolving Astigmata diverged from soil oribatid mites.

A human pluripotent stem cell-based model of SARS-CoV-2 infection reveals an ACE2-independent inflammatory activation of vascular endothelial cells through TLR4.

To date, the direct causative mechanism of SARS-CoV-2-induced endotheliitis remains unclear. Here, we report that human ECs barely express surface ACE2, and ECs express less intracellular ACE2 than non-ECs of the lungs. We ectopically expressed ACE2 in hESC-ECs to model SARS-CoV-2 infection.

Endothelial contribution to COVID-19: an update on mechanisms and therapeutic implications.

The global propagation of SARS-CoV-2 leads to an unprecedented public health emergency. Despite that the lungs are the primary organ targeted by COVID-19, systemic endothelial inflammation and dysfunction is observed particularly in patients with severe COVID-19, manifested by elevated endothelial injury markers, endotheliitis, and coagulopathy. Here, we review the clinical characteristics of COVID-19 associated endothelial dysfunction; and the likely pathological mechanisms underlying the disease including direct cell entry or indirect immune overreactions after SARS-CoV-2 infection.

Single-Cell RNA-Seq Reveals that CD9 Is a Negative Marker of Glucose-Responsive Pancreatic β-like Cells Derived from Human Pluripotent Stem Cells.

To date, it remains unclear if there are specific cell-surface markers for purifying glucose-responsive pancreatic β-like cells derived from human pluripotent stem cells (hPSCs). In searching for this, we generated an efficient protocol for differentiating β-like cells from human embryonic stem cells. We performed single-cell RNA sequencing and found that CD9 is a negative cell-surface marker of β-like cells, as most INS cells are CD9.

An emerging role of regulatory T-cells in cardiovascular repair and regeneration.

Accumulating evidence has demonstrated that immune cells play an important role in the regulation of tissue repair and regeneration. After injury, danger signals released by the damaged tissue trigger the initial pro-inflammatory phase essential for removing pathogens or cellular debris that is later replaced by the anti-inflammatory phase responsible for tissue healing. On the other hand, impaired immune regulation can lead to excessive scarring and fibrosis that could be detrimental for the restoration of organ function.

Premature Activation of Immune Transcription Programs in Autoimmune-Predisposed Mouse Embryonic Stem Cells and Blastocysts.

Autoimmune diabetes is a complex multifactorial disease with genetic and environmental factors playing pivotal roles. While many genes associated with the risk of diabetes have been identified to date, the mechanisms by which external triggers contribute to the genetic predisposition remain unclear. Here, we derived embryonic stem (ES) cell lines from diabetes-prone non-obese diabetic (NOD) and healthy C57BL/6 (B6) mice.

Specific ablation of CD4 T-cells promotes heart regeneration in juvenile mice.

Unlike adult cardiomyocytes, neonatal cardiomyocytes can readily proliferate that contributes to a transient regenerative potential after myocardial injury in mice. We have recently reported that CD4 regulatory T-cells promote this process; however, the role of other CD4 T-cell subsets as well as CD8 T-cells in postnatal heart regeneration has been less studied. by comparing the regenerating postnatal day (P) 3 and the non-regenerating P8 heart after injury, we revealed the heterogeneity of CD4 and CD8 T-cells in the myocardium through single cell analysis.

CD8 T-cell plasticity regulates vascular regeneration in type-2 diabetes.

In this study, we observe that the ischemic tissues of type-2 diabetic (T2D) patients and mice have significantly more CD8 T-cells than that of their normoglycemic counterparts, respectively. However, the role of CD8 T-cells in the pathogenesis of diabetic vascular complication has been less studied. : We employed loss-of-function studies in mouse models using the non-lytic anti-CD8 antibody that blocks tissue infiltration of CD8 T-cells into the injured tissue.

Regulatory T-cells regulate neonatal heart regeneration by potentiating cardiomyocyte proliferation in a paracrine manner.

The neonatal mouse heart is capable of transiently regenerating after injury from postnatal day (P) 0-7 and macrophages are found important in this process. However, whether macrophages alone are sufficient to orchestrate this regeneration; what regulates cardiomyocyte proliferation; why cardiomyocytes do not proliferate after P7; and whether adaptive immune cells such as regulatory T-cells (Treg) influence neonatal heart regeneration have less studied. : We employed both loss- and gain-of-function transgenic mouse models to study the role of Treg in neonatal heart regeneration.

Single-cell transcriptomics reveal that PD-1 mediates immune tolerance by regulating proliferation of regulatory T cells.

Background: We have previously reported an antigen-specific protocol to induce transplant tolerance and linked suppression to human embryonic stem cell (hESC)-derived tissues in immunocompetent mice through coreceptor and costimulation blockade. However, the exact mechanisms of acquired immune tolerance in this model have remained unclear.

Methods: We utilize the NOD.

Regulatory T Cells Promote Apelin-Mediated Sprouting Angiogenesis in Type 2 Diabetes.

The role of CD4 T cells in the ischemic tissues of T2D patients remains unclear. Here, we report that T2D patients' vascular density was negatively correlated with the number of infiltrating CD4 T cells after ischemic injury. Th1 was the predominant subset, and Th1-derived IFN-γ and TNF-α directly impaired human angiogenesis.

Phylogenetic and Structural Significance of Dihydrofolate Synthase (folC) Mutations in Drug-Resistant Mycobacterium tuberculosis.

The aim of this study is to investigate the mutation pattern of the folC gene in drug-resistant Mycobacterium tuberculosis (MTB) clinical isolates of global and Hong Kong cohorts. The public sequence read archives of 1,124 MTB genomes from three independent studies were retrieved and folC mutations existing solely in drug-resistant MTB strains were identified. A phylogenetic tree was constructed to analyze the segregation of mutation-related amino acid residues in the FolC structure.

Transcriptome analysis of different developmental stages of amphioxus reveals dynamic changes of distinct classes of genes during development.

Vertebrates diverged from other chordates approximately 500 million years ago and have adopted several modifications of developmental processes. Amphioxus is widely used in evolutionary developmental biology research, such as on the basic patterning mechanisms involved in the chordate body plan and the origin of vertebrates. The fast development of next-generation sequencing has advanced knowledge of the genomic organization of amphioxus; however, many aspects of gene regulation during amphioxus development have not been fully characterized.

Transcriptome analysis of leaves, roots and flowers of Panax notoginseng identifies genes involved in ginsenoside and alkaloid biosynthesis.

Background: Panax notoginseng (Burk.) F.H.

The draft genome, transcriptome, and microbiome of Dermatophagoides farinae reveal a broad spectrum of dust mite allergens.

Background: A sequenced house dust mite (HDM) genome would advance our understanding of HDM allergens, a common cause of human allergies.

Objective: We sought to produce an annotated Dermatophagoides farinae draft genome and develop a combined genomic-transcriptomic-proteomic approach for elucidation of HDM allergens.

Methods: A D farinae draft genome and transcriptome were assembled with high-throughput sequencing, accommodating microbiome sequences.