Intestinal stem cell maturation and development coincide with gut microbiota exposure after birth. Here, we investigated how early life microbial exposure, and disruption of this process, impacts the intestinal stem cell niche and development. Single-cell transcriptional analysis revealed impaired stem cell differentiation into Paneth cells and macrophage specification upon antibiotic treatment in early life. Mouse genetic and organoid co-culture experiments demonstrated that a CD206 subset of intestinal macrophages secreted Wnt ligands, which maintained the mesenchymal niche cells important for Paneth cell differentiation. Antibiotics and reduced numbers of Paneth cells are associated with the deadly infant disease, necrotizing enterocolitis (NEC). We showed that colonization with Lactobacillus or transfer of CD206 macrophages promoted Paneth cell differentiation and reduced NEC severity. Together, our work defines the gut microbiota-mediated regulation of stem cell niches during early postnatal development.
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http://dx.doi.org/10.1016/j.immuni.2022.11.003 | DOI Listing |
J Transl Med
January 2025
Department of Stem Cell and Regenerative Medicine, Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
Background: It is worthwhile to establish a prognostic prediction model based on microenvironment cells (MCs) infiltration and explore new treatment strategies for triple-negative breast cancer (TNBC).
Methods: The xCell algorithm was used to quantify the cellular components of the TNBC microenvironment based on bulk RNA sequencing (bulk RNA-seq) data. The MCs index (MCI) was constructed using the least absolute shrinkage and selection operator Cox (LASSO-Cox) regression analysis.
Mol Neurodegener
January 2025
Guangdong Key Laboratory of Non-Human Primate Research, Key Laboratory of CNS Regeneration (Ministry of Education), School of Medicine, GHM Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, China.
Background: HD is a devastating neurodegenerative disorder caused by the expansion of CAG repeats in the HTT. Silencing the expression of mutated proteins is a therapeutic direction to rescue HD patients, and recent advances in gene editing technology such as CRISPR/CasRx have opened up new avenues for therapeutic intervention.
Methods: The CRISPR/CasRx system was employed to target human HTT exon 1, resulting in an efficient knockdown of HTT mRNA.
J Nanobiotechnology
January 2025
Laboratorio de Medicina Nano-Regenerativa, Centro de Investigación e Innovación Biomédica (CiiB), Universidad de los Andes, Santiago, Chile.
Osteoarthritis (OA) is a joint disease characterized by articular cartilage degradation. Persistent low-grade inflammation defines OA pathogenesis, with crucial involvement of pro-inflammatory M1-like macrophages. While mesenchymal stromal cells (MSC) and their small extracellular vesicles (sEV) hold promise for OA treatment, achieving consistent clinical-grade sEV products remains a significant challenge.
View Article and Find Full Text PDFJ Exp Clin Cancer Res
January 2025
Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background: Most patients with prostate cancer inevitably progress to castration-resistant prostate cancer (CRPC), at which stage chemotherapeutics like docetaxel become the first-line treatment. However, chemotherapy resistance typically develops after an initial period of therapeutic efficacy. Increasing evidence indicates that cancer stem cells confer chemotherapy resistance via exosomes.
View Article and Find Full Text PDFRespir Res
January 2025
Department of Regenerative and Infectious Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama Chuo-ku, Hamamatsu, Shizuoka, 431-3192, Japan.
Background: Recent advances in comprehensive gene analysis revealed the heterogeneity of mouse lung fibroblasts. However, direct comparisons between these subpopulations are limited due to challenges in isolating target subpopulations without gene-specific reporter mouse lines. In addition, the properties of lung lipofibroblasts remain unclear, particularly regarding the appropriate cell surface marker and the niche capacity for alveolar epithelial cell type 2 (AT2), an alveolar tissue stem cell.
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