Enteric GABAergic neuron-derived γ-aminobutyric acid initiates expression of Igfbp7 to sustain ILC3 homeostasis.

Neuronal signals have emerged as critical factors that regulate group 3 innate lymphoid cell (ILC3) response and tissue homeostasis, but the molecular mechanisms underlying this regulation remain largely elusive. Here, we identified that the enteric GABAergic neuron-derived neurotransmitter γ-aminobutyric acid (GABA) inhibited proliferation and IL-17A production in ILC3s in a manner dependent on the GABA receptors Gabbr1 and Gabbr2. Conditional deletion of Gabbr1 or ablation of GABAergic neurons caused increased IL-17A production and aggravated colitis.

A read-through circular RNA RCRIN inhibits metabolic dysfunction-associated steatotic liver disease.

Background & Aims: The molecular mechanism underlying metabolic dysfunction-associated steatotic liver disease (MASLD) is elusive and whether non-coding RNAs can serve as biomarkers and therapeutic targets of MASLD is less defined.

Methods: Exon capture RNA sequencing analysis was used to identify read-through circRNAs (rt-circRNAs) in livers from three MASLD patients and three patients without MASLD. Hepatocyte-specific deletion or overexpression of rt-circRNA RCRIN were utilized to study MASLD pathogenesis.

Noncoding RNAs in tumorigenesis and tumor therapy.

Tumorigenesis is a complicated process in which numerous modulators are involved in different ways. Previous studies have focused primarily on tumor-associated protein-coding genes such as oncogenes and tumor suppressor genes, as well as their associated oncogenic pathways. However, noncoding RNAs (ncRNAs), rising stars in diverse physiological and pathological processes, have recently emerged as additional modulators in tumorigenesis.

Circular RNA circTmem241 drives group III innate lymphoid cell differentiation via initiation of Elk3 transcription.

Innate lymphoid cells (ILCs) exert important roles in host defense, tissue repair and inflammatory diseases. However, how ILC lineage specification is regulated remains largely elusive. Here we identify that circular RNA circTmem241 is highly expressed in group III innate lymphoid cells (ILC3s) and their progenitor cells.

5-hydroxytryptamine produced by enteric serotonergic neurons initiates colorectal cancer stem cell self-renewal and tumorigenesis.

Colorectal cancer stem cells (CSCs) contribute to colorectal tumorigenesis and metastasis. Colorectal CSCs reside within specialized niches and harbor self-renewal and differentiation capacities. However, the niche regulations of CSCs remain unclear.

Gut microbiota drives macrophage-dependent self-renewal of intestinal stem cells via niche enteric serotonergic neurons.

Lgr5 intestinal stem cells (ISCs) reside within specialized niches at the crypt base and harbor self-renewal and differentiation capacities. ISCs in the crypt base are sustained by their surrounding niche for precise modulation of self-renewal and differentiation. However, how intestinal cells in the crypt niche and microbiota in enteric cavity coordinately regulate ISC stemness remains unclear.

Intestinal Tuft-2 cells exert antimicrobial immunity via sensing bacterial metabolite N-undecanoylglycine.

Tuft cells are a type of intestinal epithelial cells that exist in epithelial barriers and play a critical role in immunity against parasite infection. It remains insufficiently clear whether Tuft cells participate in bacterial eradication. Here, we identified Sh2d6 as a signature marker for CD45 Tuft-2 cells.

Induction of functional neutrophils from mouse fibroblasts by thymidine through enhancement of Tet3 activity.

Neutrophils are derived from bone marrow hematopoietic stem cells (HSCs) and are the largest population among circulating white blood cells in humans, acting as the first line of defense against invading pathogens. Whether neutrophils can be generated by transdifferentiation strategies is unknown. Here, we show that thymidine induces the conversion of mouse fibroblasts to neutrophils.

N-methyladenosine methylation in tRNA drives liver tumourigenesis by regulating cholesterol metabolism.

Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers and is characterized by high recurrence and heterogeneity, yet its mechanism is not well understood. Here we show that N-methyladenosine methylation (mA) in tRNA is remarkably elevated in hepatocellular carcinoma (HCC) patient tumour tissues. Moreover, mA methylation signals are increased in liver cancer stem cells (CSCs) and are negatively correlated with HCC patient survival.

Circular RNA circIPO11 drives self-renewal of liver cancer initiating cells via Hedgehog signaling.

Background: Hepatocellular carcinoma (HCC) is one of the most intractable tumors in the world due to its high rate of recurrence and heterogeneity. Liver cancer initiating cells also called cancer stem cells (CSCs) play a critical role in resistance against typical therapy and high tumor-initiating potential. However, the role of the novel circular RNA (circRNA) circIPO11 in the maintenance of liver cancer initiating cells remains elusive.

Circular RNA cia-MAF drives self-renewal and metastasis of liver tumor-initiating cells via transcription factor MAFF.

Liver tumor-initiating cells (TICs) are involved in liver tumorigenesis, metastasis, drug resistance, and relapse, but the regulatory mechanisms of liver TICs are largely unknown. Here, we have identified a functional circular RNA, termed circRNA activating MAFF (cia-MAF), that is robustly expressed in liver cancer and liver TICs. cia-MAF-KO primary cells and cia-maf-KO liver tumors harbor decreased ratios of TICs, and display impaired liver tumorigenesis, self-renewal, and metastatic capacities.

Identification of cis-HOX-HOXC10 axis as a therapeutic target for colorectal tumor-initiating cells without APC mutations.

Colorectal cancer (CRC) is one of the most common cancers worldwide, in which adenomatous polyposis coli (APC) mutations are frequently and uniquely observed. Here we find that cis-HOX (circular RNA stabilizing HOXC10) is robustly expressed in colorectal tumor-initiating cells (TICs). cis-HOX knockout decreases colorectal TIC numbers and impairs the self-renewal, tumorigenesis, and metastatic capacities of TICs, whereas cis-HOX overexpression drives colorectal TIC self-renewal and metastasis.

Circular RNA circZbtb20 maintains ILC3 homeostasis and function via Alkbh5-dependent mA demethylation of Nr4a1 mRNA.

Group 3 innate lymphoid cells (ILC3s) play critical roles in innate immunity and gut homeostasis. However, how ILC3 homeostasis is regulated remains elusive. Here, we identified a novel circular RNA, circZbtb20, that is highly expressed in ILC3s and required for their maintenance and function.

An inducible circular RNA circKcnt2 inhibits ILC3 activation to facilitate colitis resolution.

Group 3 innate lymphoid cells (ILC3) are an important regulator for immunity, inflammation and tissue homeostasis in the intestine, but how ILC3 activation is regulated remains elusive. Here we identify a new circular RNA (circRNA) circKcnt2 that is induced in ILC3s during intestinal inflammation. Deletion of circKcnt2 causes gut ILC3 activation and severe colitis in mice.

Correction: Transdifferentiation of tumor infiltrating innate lymphoid cells during progression of colorectal cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The chromatin remodeler SRCAP promotes self-renewal of intestinal stem cells.

Lgr5 intestinal stem cells (ISCs) exhibit self-renewal and differentiation features under homeostatic conditions, but the mechanisms controlling Lgr5 + ISC self-renewal remain elusive. Here, we show that the chromatin remodeler SRCAP is highly expressed in mouse intestinal epithelium and ISCs. Srcap deletion impairs both self-renewal of ISCs and intestinal epithelial regeneration.

[Mismatch of ASPECTS based on arterial spin labeling and diffusion-weighted imaging as an indicator for mechanical thrombectomy in patients with wake-up stroke].

Objective: To retrospectively analyze the outcomes of wake-up stroke (WUS) patients with occlusion of large vessel occlusion (LVO), who were selected for mechanical thrombectomy according to the mismatch of Alberta Stroke Program Early CT Score (ASPECTS) based on arterial spin labeling (ASL) and diffusion-weighted image (DWI) on admission magnetic resonance (MR) scans.

Methods: Twelve consecutive WUS patients with acute LVO of the anterior circulation undergoing MR scans with ASL and DWI prior to thrombectomy were retrospectively evaluated. The mismatch of ASPECTS was defined as the difference between ASL-ASPECTS and DWI-ASPECTS, and a higher score indicates a greater mismatch.

Transdifferentiation of tumor infiltrating innate lymphoid cells during progression of colorectal cancer.

Innate lymphoid cells (ILCs) reside in mucosal surfaces to potentiate immune responses, sustain mucosal integrity and maintain tissue homeostasis. However, how tumor infiltrating ILCs modulate tumor development and progression is unclear. Here we profiled tumor infiltrating ILCs during colorectal cancer (CRC) progression by single-cell RNA sequencing.

Glutamylation of deubiquitinase BAP1 controls self-renewal of hematopoietic stem cells and hematopoiesis.

All hematopoietic lineages are derived from a limited pool of hematopoietic stem cells (HSCs). Although the mechanisms underlying HSC self-renewal have been extensively studied, little is known about the role of protein glutamylation and deglutamylation in hematopoiesis. Here, we show that carboxypeptidase CCP3 is most highly expressed in BM cells among CCP members.

SPRY4 is responsible for pathogenesis of adolescent idiopathic scoliosis by contributing to osteogenic differentiation and melatonin response of bone marrow-derived mesenchymal stem cells.

Adolescent idiopathic scoliosis (AIS) is a complex, three-dimensional deformity of the spine that commonly occurs in pubescent girls. Decreased osteogenic differentiation and aberrant melatonin signalling have been demonstrated in mesenchymal stem cells (MSCs) from AIS patients and are implicated in the pathogenesis of AIS. However, the molecular mechanisms underlying these abnormal cellular features remain largely unknown.