mA Reader PRRC2A Promotes Colorectal Cancer Progression via CK1ε-Mediated Activation of WNT and YAP Signaling Pathways.

Colorectal cancer (CRC) is the third most common cancer type and the second highest mortality rate among cancers. However, the mechanisms underlying CRC progression remain to be fully understood. In this work, a recently identified mA-modified RNA reader protein Proline-rich Coiled-coil 2a (PRRC2A) is markedly upregulated in CRC, and intestinal epithelium-specific deletion of Prrc2a significantly suppressed tumor cell growth, stemness, and migratory capacity, while its overexpression promoted these behaviors.

Polycomb group protein Mel18 inhibits hematopoietic stem cell self-renewal through repressing the transcription of self-renewal and proliferation genes.

Polycomb group (PcG) proteins play important roles in hematopoietic stem cell (HSC) self-renewal. Mel18 and Bmi1 are homologs of the PCGF subunit within the Polycomb repressive complex 1 (PRC1). Bmi1 (PCGF4) enhances HSC self-renewal and promotes terminal differentiation.

mA-modified cenRNA stabilizes CENPA to ensure centromere integrity in cancer cells.

mA modification is best known for its critical role in controlling multiple post-transcriptional processes of the mRNAs. Here, we discovered elevated levels of mA modification on centromeric RNA (cenRNA) in cancerous cells compared with non-cancerous cells. We then identified CENPA, an H3 variant, as an mA reader of cenRNA.

The efficient generation of functional human hepatocytes from chemically induced pluripotent stem cells.

Derivation of human hepatocytes from pluripotent stem cells in vitro has important applications including cell therapy and drug discovery. However, the differentiation of pluripotent stem cells into hepatocytes in vitro was not well recapitulated the development of liver. Here, we developed a differentiation protocol by mimicking the two-stage development of hepatoblasts, which permits the efficient generation of hepatic progenitor cells from chemically induced pluripotent stem cells (hCiPSCs).

Molecular signatures define subtypes of auditory afferents with distinct peripheral projection patterns and physiological properties.

Type I spiral ganglion neurons (SGNs) are the auditory afferents that transmit sound information from cochlear inner hair cells (IHCs) to the brainstem. These afferents consist of physiological subtypes that differ in their spontaneous firing rate (SR), activation threshold, and dynamic range and have been described as low, medium, and high SR fibers. Lately, single-cell RNA sequencing experiments have revealed three molecularly defined type I SGN subtypes.

Establishment and validation of exhausted CD8+ T cell feature as a prognostic model of HCC.

Objectives: The exhausted CD8+T (Tex) cells are a unique cell population of activated T cells that emerges in response to persistent viral infection or tumor antigens. Tex cells showed the characteristics of aging cells, including weakened self-renewal ability, effector function inhibition, sustained high expression of inhibitory receptors including PD-1, TIGIT, TIM-3, and LAG-3, and always accompanied by metabolic and epigenetic reprogramming. Tex cells are getting more and more attention in researching immune-related diseases and tumor immunotherapy.

HE4 overexpression in mice leads to leydig cell hyperplasia and spermatogensis impairment: Pathological implications for oligospermia.

Previous studies have shown that HE4 cancer biomarker promoted cancer cell proliferation and tumor growth in mouse xenograft models. Interestingly, HE4 levels are significantly increased in the seminal plasma of oligoasthenospermia patients, raising a question on HE4 role(s) in spermatogenesis. We constructed an HE4 overexpression mouse model (HE4-OE), and observed that HE4-OE male adult mice had small testes, low sperm counts, and elevated serum/testis testosterone levels.

Exploration and verification of COVID-19-related hub genes in liver physiological and pathological regeneration.

An acute injury is often accompanied by tissue regeneration. In this process, epithelial cells show a tendency of cell proliferation under the induction of injury stress, inflammatory factors, and other factors, accompanied by a temporary decline of cellular function. Regulating this regenerative process and avoiding chronic injury is a concern of regenerative medicine.

Reanalysis of ribosome profiling datasets reveals a function of rocaglamide A in perturbing the dynamics of translation elongation via eIF4A.

The quickly accumulating ribosome profiling data is an insightful resource for studying the critical details of translation regulation under various biological contexts. Rocaglamide A (RocA), an antitumor heterotricyclic natural compound, has been shown to inhibit translation initiation of a large group of mRNA species by clamping eIF4A onto poly-purine motifs in the 5' UTRs. However, reanalysis of previous ribosome profiling datasets reveals an unexpected shift of the ribosome occupancy pattern, upon RocA treatment in various types of cells, during early translation elongation for a specific group of mRNA transcripts without poly-purine motifs over-represented in their 5' UTRs.

Microglial safeguards postnatal integrity of the cortex and sociability.

Microglial abnormalities may contribute to neurodevelopmental disorders. PTEN is implicated as a susceptibility gene for autism spectrum disorders and its germline ablation in mice causes behavioral abnormalities. Here we find postnatal PTEN deletion in microglia causes deficits in sociability and novel object recognition test.

A Novel Computational Biomechanics Framework to Model Vascular Mechanopropagation in Deep Bone Marrow.

The mechanical stimuli generated by body exercise can be transmitted from cortical bone into the deep bone marrow (mechanopropagation). Excitingly, a mechanosensitive perivascular stem cell niche is recently identified within the bone marrow for osteogenesis and lymphopoiesis. Although it is long known that they are maintained by exercise-induced mechanical stimulation, the mechanopropagation from compact bone to deep bone marrow vasculature remains elusive of this fundamental mechanobiology field.

USP15 promotes cGAS activation through deubiquitylation and liquid condensation.

Double-stranded DNA (dsDNA) is recognized as a danger signal by cyclic GMP-AMP synthase (cGAS), which triggers innate immune responses. cGAS activity must be properly regulated to maintain immune homeostasis. However, the mechanism by which cGAS activation is controlled remains to be better understood.

A surface-receptor-coupled G protein regulates plant immunity through nuclear protein kinases.

Plants employ cell-surface-localized pattern recognition receptors (PRRs) to recognize immunogenic patterns and activate defenses. How these receptors regulate immune signaling in the nucleus is not well understood. Our previous studies showed that BIK1, a central kinase associated with PRRs, phosphorylates a plant-specific Gα protein called extra-large G protein 2 (XLG2) to positively regulate immunity.

De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data.

Identification of open reading frames (ORFs), especially those encoding small peptides and being actively translated under specific physiological contexts, is critical for comprehensive annotations of context-dependent translatomes. Ribosome profiling, a technique for detecting the binding locations and densities of translating ribosomes on RNA, offers an avenue to rapidly discover where translation is occurring at the genome-wide scale. However, it is not a trivial task in bioinformatics to efficiently and comprehensively identify the translating ORFs for ribosome profiling.

Whole-Brain Reconstruction of Neurons in the Ventral Pallidum Reveals Diverse Projection Patterns.

The ventral pallidum (VP) integrates reward signals to regulate cognitive, emotional, and motor processes associated with motivational salience. Previous studies have revealed that the VP projects axons to many cortical and subcortical structures. However, descriptions of the neuronal morphologies and projection patterns of the VP neurons at the single neuron level are lacking, thus hindering the understanding of the wiring diagram of the VP.

Mechanical communication in fibrosis progression.

Mechanical hallmarks of fibrotic microenvironments are both outcomes and causes of fibrosis progression. Understanding how cells sense and transmit mechanical cues in the interplay with extracellular matrix (ECM) and hemodynamic forces is a significant challenge. Recent advances highlight the evolvement of intracellular mechanotransduction pathways responding to ECM remodeling and abnormal hemodynamics (i.

Bmi1 Regulates Wnt Signaling in Hematopoietic Stem and Progenitor Cells.

Polycomb group protein Bmi1 is essential for hematopoietic stem cell (HSC) self-renewal and terminal differentiation. However, its target genes in hematopoietic stem and progenitor cells are largely unknown. We performed gene expression profiling assays and found that genes of the Wnt signaling pathway are significantly elevated in Bmi1 null hematopoietic stem and progenitor cells (HSPCs).

Entry of hepatitis B virus: going beyond NTCP to the nucleus.

Hepatitis B virus (HBV) infection remains a major cause of liver diseases and hepatocellular carcinoma. HBV infection begins by low-affinity attachment to hepatocytes and subsequent binding with a specific receptor sodium taurocholate cotransporting polypeptide (NTCP) on sinusoidal-basolateral side of liver parenchymal cells. Following internalization with an unclear mechanism, HBV undergoes uncoating, capsid disassembling and culminates in delivering its genome into the nucleus and forms the covalently closed circular (ccc) DNA.

Identification of the cross-strand chimeric RNAs generated by fusions of bi-directional transcripts.

A major part of the transcriptome complexity is attributed to multiple types of DNA or RNA fusion events, which take place within a gene such as alternative splicing or between different genes such as DNA rearrangement and trans-splicing. In the present study, using the RNA deep sequencing data, we systematically survey a type of non-canonical fusions between the RNA transcripts from the two opposite DNA strands. We name the products of such fusion events cross-strand chimeric RNA (cscRNA).

Identification of Protein Direct Interactome with Genetic Code Expansion and Search Engine OpenUaa.

Protein crosslinks occur endogenously such as modifications by ubiquitin-like proteins for signaling, or exogenously through genetically encoded chemical crosslinkers (GECX) for studying elusive protein-protein interactions. However, it remains challenging to identify these protein crosslinks efficiently at the proteomic scale. Herein, software OpenUaa is developed for identifying protein crosslinks generated by genetically encoded unnatural amino acids and endogenous protein conjugation.

In vivo chemical reprogramming of astrocytes into neurons.

In mammals, many organs lack robust regenerative abilities. Lost cells in impaired tissue could potentially be compensated by converting nearby cells in situ through in vivo reprogramming. Small molecule-induced cell reprogramming offers a temporally flexible and non-integrative strategy for altering cell fate, which is, in principle, favorable for in vivo reprogramming in organs with notoriously poor regenerative abilities, such as the brain.

Mutual dependency between lncRNA LETN and protein NPM1 in controlling the nucleolar structure and functions sustaining cell proliferation.

Fundamental processes such as ribosomal RNA synthesis and chromatin remodeling take place in the nucleolus, which is hyperactive in fast-proliferating cells. The sophisticated regulatory mechanism underlying the dynamic nucleolar structure and functions is yet to be fully explored. The present study uncovers the mutual functional dependency between a previously uncharacterized human long non-coding RNA, which we renamed LETN, and a key nucleolar protein, NPM1.

FWAVina: A novel optimization algorithm for protein-ligand docking based on the fireworks algorithm.

Protein-ligand docking is an essential process that has accelerated drug discovery. How to accurately and effectively optimize the predominant position and orientation of ligands in the binding pocket of a target protein is a major challenge. This paper proposed a novel ligand binding pose search method called FWAVina based on the fireworks algorithm, which combined the fireworks algorithm with the efficient Broyden-Fletcher-Goldfarb-Shannon local search method adopted in AutoDock Vina to address the pose search problem in docking.