SARS-CoV-2 induced vascular endothelial dysfunction: direct or indirect effects?

Clinical evidence reveals that manifestations of endothelial dysfunction are widely observed in COVID-19 and long-COVID patients. However, whether these detrimental effects are caused by direct infection of the endothelium or are indirectly mediated by systemic inflammation has been a matter of debate. It has been well acknowledged that endothelial cells (ECs) of the cardiovascular system ubiquitously express the SARS-CoV-2 entry receptor angiotensin-converting enzyme 2 (ACE2), yet accumulating evidence suggests that it is more predominantly expressed by pericytes and vascular smooth muscle cells of the mammalian blood vessel.

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.

A differentiation protocol for the generation of pancreatic beta-like cells from human embryonic stem cells.

By virtue of their capability to replicate and regenerate, human stem-cell-derived beta-like cells could be a valuable resource for cellular therapy targeting insulin-dependent diabetes. Here, we present a protocol to generate beta-like cells from human embryonic stem cells (hESCs). We first describe steps for differentiation of beta-like cells from hESCs and CD9-negative beta-like cell enrichment through fluorescence-activated cell sorting.

The role of m6A mRNA modification in normal and malignant hematopoiesis.

Hematopoiesis is a highly orchestrated biological process sustaining the supply of leukocytes involved in the maintenance of immunity, O2 and CO2 exchange, and wound healing throughout the lifetime of an animal, including humans. During early hematopoietic cell development, several waves of hematopoiesis require the precise regulation of hematopoietic ontogeny as well as the maintenance of hematopoietic stem and progenitor cells in the hematopoietic tissues, such as the fetal liver and bone marrow. Recently, emerging evidence has suggested the critical role of m6A messenger RNA (mRNA) modification, an epigenetic modification dynamically regulated by its effector proteins, in the generation and maintenance of hematopoietic cells during embryogenesis.

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.

Phosphorylation of Msx1 promotes cell proliferation through the Fgf9/18-MAPK signaling pathway during embryonic limb development.

Msh homeobox (Msx) is a subclass of homeobox transcriptional regulators that control cell lineage development, including the early stage of vertebrate limb development, although the underlying mechanisms are not clear. Here, we demonstrate that Msx1 promotes the proliferation of myoblasts and mesenchymal stem cells (MSCs) by enhancing mitogen-activated protein kinase (MAPK) signaling. Msx1 directly binds to and upregulates the expression of fibroblast growth factor 9 (Fgf9) and Fgf18.

Emerin anchors Msx1 and its protein partners at the nuclear periphery to inhibit myogenesis.

Background: Previous studies have shown that in myogenic precursors, the homeoprotein Msx1 and its protein partners, histone methyltransferases and repressive histone marks, tend to be enriched on target myogenic regulatory genes at the nuclear periphery. The nuclear periphery localization of Msx1 and its protein partners is required for Msx1's function of preventing myogenic precursors from pre-maturation through repressing target myogenic regulatory genes. However, the mechanisms underlying the maintenance of Msx1 and its protein partners' nuclear periphery localization are unknown.