Homeobox domain transcription factors are proteins that have a region with a specific structure that binds a specific DNA sequence within a gene. These transcriptions factors play a known role in development. More specifically, the POU family of homeobox domain transcription factors play important roles in the development of multiple tissue types including sensory tissues. Mutations in the POU4F3 gene are known to cause a dominant form of hereditary hearing loss in humans. Researchers used whole transcriptome profiling to discover that POU4F3 and POU4F1 are selectively expressed in Merkel cells (MCs), which are specialized touch sensors, from both neonatal and adult mouse skin. Using genetically engineered knockout mice, they determined that POU4F3 is critical for MC development, while POU4F1 is expressed in MCs but not necessary for their development.

The metabolic enzyme PKM2 accumulates in the nucleus in various cancer cells. In this study, researchers found that PKM2 binds to structures called G-quadruplexes (rG4) forming on precursor mRNAs. The balance of folded and unfolded rG4s controls the transcriptional output of rG4-containing RNAs (rG4ome). The rG4ome encodes components related to epithelial-to-mesenchymal transition (e.g., a process that allows tumors to grow and spread) and higher rG4 levels, which are associated with poorer patient survival outcomes in different cancer types. Further, removing PKM2 from the nucleus reduces tumor growth and metastasis.

This study examines how a specific metabolic pathway, called the Aconitate Decarboxylase 1/Itaconate pathway, affects the immune system in people with systemic lupus erythematosus (SLE). The researchers found that this pathway is involved in the immune system dysfunction in animal models of lupus and is also linked to markers that indicate heart disease risk and lupus disease activity levels in people with SLE.

Neutrophil depletion and deregulation are directly linked to development of diabetic foot ulcers (DFU). Scientists used a streptozotocin-treated hyperglycemic (high blood glucose/sugar) mouse model to study how overexpression of SOX2 in the skin affects wound healing. The researchers found that the combination of SOX2 upregulation and hyperglycemia in skin cells called keratinocytes triggers a pro-healing signature and increased neutrophil migration. The results highlight SOX2-mediated gene expression as a potential means of addressing neutrophil depletion in DFU.

Genes are expressed through tightly controlled processes. The first step of gene expression is transcription, a cellular process by which a gene's DNA sequence is copied into RNA. Transcriptional bursting is a fundamental property of genes that allows large amounts of RNA to be produced in a short period of time. This process has been observed in diverse organisms, from bacteria to mammals. In this study, the researchers applied mathematical modeling to single-cell RNA sequencing data—information on the transcriptional activity of individual cells—to infer transcriptional bursting dynamics under multiple conditions. The researchers found that Mediator complex subunit 26 (MED26) had the most profound impact on the entire gene regulatory network, acting downstream of chromatin spatial architecture without affecting TATA box-binding protein recruitment, a key step that helps recruits transcription machinery to the gene. These findings suggest that later steps in the initiation of transcriptional bursts are primary nodes for integrating gene networks in single cells.

Familial hemophagocytic lymphohistiocytosis (HLH) is a life-threatening cytokine storm syndrome caused by recessive, loss of function variants of genes in the pathway that controls the processing of cytolytic granule processing pathway genes. Heterozygous variants in these genes contribute to a secondary form of HLH (macrophage activation syndrome, MAS) that frequently develops in children with systemic juvenile idiopathic arthritis (sJIA). To evaluate the relationship between HLH gene variation and sJIA without MAS, HLH genes were sequenced and compared between 524 patients with sJIA and 2,924 control patients.

Spondyloarthritis (SpA) is an inflammatory disease that affects the gastrointestinal tract, skeleton, and eyes. HLA-B27 is a major risk gene for SpA, but the underlying mechanisms are unclear. One hypothesis is that HLA-B27 promotes SpA through misfolding-induced endoplasmic reticulum (ER) stress that in turn upregulates IL-23 expression via the transcription factor CHOP. In this study, the researchers knocked out CHOP expression in an animal model of HLA-B27-associated SpA. Despite reduced IL-23 production, gut inflammation did not improve, indicating that the gut disease did not occur as a result of ER stress-induced IL-23 production.

A team of researchers in the Dermatology Consultation Service analyzed tissue samples from 60 of 112 study participants who were referred to the NIH Clinical Center in Bethesda, MD, for suspected VEXAS syndrome. The most reported findings included inflammation of the small blood vessels of the skin, known as leukocystoclastic vasculitis, fever and a painful rash known as neutrophilic dermatosis, and inflammation of the skin around the blood vessels, known as perivascular dermatitis.

In this report, researchers described a deep neural generative framework, the dynamic batching adversarial autoencoder (DB-AAE), which excels at denoising scRNA-seq datasets. DB-AAE directly captures optimal features from input data and enhances feature preservation, including cell type-specific gene expression patterns.