Publication

Patch‐to‐Seq Reveals Unique Transcriptomic Profiles of Chemosensitive Serotonergic Neurons

Central respiratory chemoreceptors are specialized neurons with intrinsic sensitivity to hypercapnia and/or acidosis that couple breathing and pH/CO2 levels. Prior data indicate that a sub-population of brainstem serotonin (5-HT) neurons are likely central respiratory chemoreceptors. However, it remains unclear which 5-HT neurons develop chemosensitivity and what molecular markers may identify this unique sub-population of 5-HT neurons.

Single-cell transcriptomics identifies limbal stem cell population and cell types mapping its differentiation trajectory in limbal basal epithelium of human cornea

Purpose This study aimed to uncover novel cell types in heterogenous basal limbus of human cornea for identifying LSC at single cell resolution. Methods Single cells of human limbal basal epithelium were isolated from young donor corneas. Single-cell RNA-Sequencing was performed using 10x Genomics platform, followed by clustering cell types through the graph-based visualization method UMAP and unbiased computational informatic analysis.

Neurod4 converts endogenous neural stem cells to neurons with synaptic formation after spinal cord injury

The transcriptome analysis of injured Xenopus laevis tadpole and mice suggested that Neurod4L.S., a basic-helix-loop-helix transcription factor, was the most promising transcription factor to exert neuroregeneration after spinal cord injury (SCI) in mammals. We generated a pseudotyped retroviral vector with the neurotropic lymphocytic choriomeningitis virus (LCMV) envelope to deliver murine Neurod4 to mice undergoing SCI. SCI induced ependymal cells to neural stem cells (NSCs) in the central canal.

Expression profile of intestinal stem cell and cancer stem cell markers in gastric cancers with submucosal invasion

Cancer stem cells (CSCs) are believed to be responsible for tumor growth, invasion, and metastasis. Submucosal invasion, which greatly enhances metastasis risk, is a critical step in gastric cancer (GC) progression. To identify stem cell-related markers associated with submucosal invasion and lymph node (LN) metastasis in GCs, we investigated the expression of candidate CSC markers (CD133, CD44, and ALDH1A) and intestinal stem cell (ISC) markers (EPHB2, OLFM4, and LGR5) in early GCs that manifested submucosal invasion.

Self-assembled mRNA vaccines

mRNA vaccines have evolved from being a mere curiosity to emerging as COVID-19 vaccine front-runners. Recent advancements in the field of RNA technology, vaccinology, and nanotechnology have generated interest in delivering safe and effective mRNA therapeutics. In this review, we discuss design and self-assembly of mRNA vaccines. Self-assembly, a spontaneous organization of individual molecules, allows for design of nanoparticles with customizable properties.

Histamine H2 receptor negatively regulates oligodendrocyte differentiation in neonatal hypoxic-ischemic white matter injury

Neonatal hypoxic-ischemic encephalopathy (HIE) with the pathological characteristic of white matter injury often leads to lifelong cognitive and neurobehavioral dysfunction, but relevant therapies to promote remyelination are still unavailable. We found that histamine H2 receptor (H2R) negatively regulated the oligodendrocyte differentiation rate without affecting the oligodendrocytes at the oligodendrocyte precursor cell stage or mature stage following oxygen-glucose deprivation in vitro.

Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity

There is a vital need for authentic COVID-19 animal models to enable the pre-clinical evaluation of candidate vaccines and therapeutics. Here we report a dose titration study of SARS-CoV-2 in the ferret model. After a high (5 × 106 pfu) and medium (5 × 104 pfu) dose of virus is delivered, intranasally, viral RNA shedding in the upper respiratory tract (URT) is observed in 6/6 animals, however, only 1/6 ferrets show similar signs after low dose (5 × 102 pfu) challenge.

On the functional relevance of spatiotemporally-specific patterns of experience-dependent long noncoding RNA expression in the brain

The majority of transcriptionally active RNA derived from the mammalian genome does not code for protein. Long noncoding RNA (lncRNA) is the most abundant form of noncoding RNA found in the brain and is involved in many aspects of cellular metabolism. Beyond their fundamental role in the nucleus as decoys for RNA-binding proteins associated with alternative splicing or as guides for the epigenetic regulation of protein-coding gene expression, recent findings indicate that activity-induced lncRNAs also regulate neural plasticity.

Expression analysis of neuropeptide FF receptors on neuroendocrine-related neurons in the rat brain using highly sensitive in situ hybridization

RF-amide peptides, a family of peptides characterized by a common carboxy-terminal Arg-Phe-NH2 motif, play various physiological roles in the brain including the modulation of neuroendocrine signaling. Neuropeptide FF (NPFF) receptors exhibit a high affinity for all RF-amide peptides, which suggests that the neurons expressing these NPFF receptors may have multiple functions in the brain. However, the distribution of the neurons expressing NPFF receptors in the rat brain remains poorly understood.

Hypoxia-induced suppression of alternative splicing of MBD2 promotes breast cancer metastasis via activation of FZD1

Metastasis is responsible for the majority of breast cancer (BrCa) deaths; however, the mechanisms underlying metastasis in this disease remain largely elusive. Here we report that under hypoxic conditions, alternative splicing of MBD2 is suppressed, favoring the production of MBD2a which facilitates BrCa metastasis. Specifically, MBD2a promoted, whereas its lesser known short form MBD2c suppressed metastasis. Activation of HIF-1 under hypoxia facilitated MBD2a production via repression of SRSF2-mediated alternative splicing.

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