Lrrc15 siRNA_Lentivectors
- Known as:
- Lrrc15 siRNA_Lentivectors
- Catalog number:
- i062755a
- Product Quantity:
- 500ng
- Category:
- -
- Supplier:
- ABM
- Gene target:
- Lrrc15 siRNA_Lentivectors
Related genes to: Lrrc15 siRNA_Lentivectors
- Gene:
- LRRC15 NIH gene
- Name:
- leucine rich repeat containing 15
- Previous symbol:
- -
- Synonyms:
- LIB
- Chromosome:
- 3q29
- Locus Type:
- gene with protein product
- Date approved:
- 2003-04-25
- Date modifiied:
- 2015-08-27
Related products to: Lrrc15 siRNA_Lentivectors
Related articles to: Lrrc15 siRNA_Lentivectors
- Pancreatic intraepithelial neoplasia (PanIN) precedes pancreatic cancer, a deadly disease characterized by an extensive tumor microenvironment. How the microenvironment evolves during cancer progression is largely unknown, as PanINs are microscopic and non-diseased pancreas samples are exceedingly rare, while adjacent normal samples are disrupted by the presence of malignancy. Leveraging donor organs and spatial technologies we mapped the evolution of PanIN to cancer. The PanIN epithelial component falls on a continuum with cancer while the PanIN microenvironment is drastically distinct. Progression to cancer is accompanied by profound geographical reorganization of myeloid cells and lymphocytes and the formation of a cancer-specific fibroblast population characterized by high levels of Smooth Muscle Actin, LRRC15 and the WNT signaling component LEF1. Together, our data show asynchronous evolution of epithelial and stromal components during pancreatic carcinogenesis. Lack of stromal reprogramming might explain why most PanINs do not progress to cancer. Compiled data available at https://pascadimagliano-lab.github.io/PancAtlas. - Source: PubMed
Publication date: 2026/05/21
Elhossiny Ahmed MKadiyala PadmaOkoye Jude OgechukwuHiraki Harrison LProcario Megan CGiridharan ThejaswiniWatkoske Hannah RTannus Ruckert MarianaWang JiayueGriffith Brian DBray Alexander WMills Jamie NEspinoza Carlos EZeller JörgPeterson NicoleBednar FilipZhang YaqingRao ArvindLyssiotis Costas ASzczepanski Julianne MShi JiaqiDeshpande AtulMaitra AnirbanFertig Elana JCarpenter Eileen SFrankel Timothy LPasca di Magliano Marina - Fibroblasts are key potentiators of chronic disease pathophysiology. Despite their established roles in promoting pathological inflammation and tissue remodeling, activated myofibroblasts are generally characterized as a single, homogeneous cell population, obscuring critical functional distinctions. Defining the cell states, their molecular regulators, and restricted markers is critical to developing effective therapies for the treatment of fibrosis. Here, using a human lung stromal cell atlas of idiopathic pulmonary fibrosis, we identify two myofibroblast transcriptional states associated with distinct predicted biological function, regulation, and cell surface marker expression. We identify fibroblast-specific TGFb signaling as the key regulator of the mechanistic switch from a wound healing-associated and proliferative to a profibrotic myofibroblast. Further, we elucidate conserved TGFb-dependent and suppressed gene expression programs that define these states. Our findings reveal that LRRC15 is highly restricted to myofibroblasts that primarily express an extracellular matrix-remodeling gene program and illuminate that this key cell state can differentiate in the absence of an obligate inflammatory precursor intermediate. Last, we apply machine learning using a human single-cell foundation model to demonstrate broad applicability of the biology described herein to human chronic disease. - Source: PubMed
Publication date: 2026/05/20
Shyer Justin AWehbe FabienDavidson Christopher DBender Hannah SThai MinhCox ChristianMissarova AlsuArlantico AlexanderHall BenZhang RuoyuKim DavidAltieri AnthonyHasan ShakirNamdar AfshinChen TinaHakim Shaheed WGuidos CynthiaBrightbill Hans DKuo TonyHeimberg GrahamCorrada Bravo HéctorRatsimandresy Rojo AUttarwar SalilTeng GraceSalem OmarArjomandi MehrdadWilson Mark SDarmanis SpyrosZiai JamesScherl AlexisModrusan ZoraWolters Paul JBuechler Matthew BVander Heiden Jason ATurley Shannon J - Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly immunosuppressive and desmoplastic tumor microenvironment (TME) that limits the efficacy of immunotherapy. However, the evolution of this immunosuppressive TME and the underlying mechanisms remain incompletely understood. Here, we construct a dynamic single-cell atlas spanning uninvolved adjacent pancreatic tissue (UNIN), intraductal papillary mucinous neoplasm (IPMN), and PDAC. We confirm the stepwise establishment of an immunosuppressive milieu, accompanied by the emergence of LRRC15 fibroblasts as determinants. Functional assays further identify tumor-derived LAMB3 as a regulator of LRRC15 fibroblast differentiation. Mechanistically, LAMB3 promotes FOSL2-dependent transcriptional activation of LRRC15 through the ITGB1/FAK/MAPK signaling axis, ultimately suppressing T cell cytotoxicity. Orthotopic models reveal that LAMB3 overexpression increases the LRRC15 positive area and impairs T cell cytotoxicity, whereas FAK inhibition partially reverses these effects. In parallel, LAMB3 knockdown reduces the LRRC15 positive area and improves the efficacy of PD-1 blockade. Moreover, glycolytic reprogramming in PDAC ductal cells upregulates LAMB3 expression and correlates with increased LRRC15 fibroblast enrichment. Clinically, co-enrichment of LAMB3 PDAC ductal cells and LRRC15 fibroblasts is associated with inferior overall survival. Collectively, our findings define a dynamic ductal-fibroblast-immune multicellular axis underlying PDAC pathogenesis and provide insights into potential therapeutic strategies. - Source: PubMed
Publication date: 2026/05/19
Shi XuqingLiu HangqiSun JianruLiu XiaodingJv XinpingChen LongyunZhang YuhanZhang HuiXing XudongLi RuiyuKe XinyiWang JunYin XianglinLiu BohanLiu QixianWang YuanLu JunliangLiu ShiyiPang JunyiCai YumengDai MenghuaBai FanWu HuanwenLiang Zhiyong - Type II diabetes mellitus (T2DM) is one of the most prevalent diseases in the United States and is associated with diabetic foot ulcers (DFU) and their impaired, often chronic, wound healing. The T2DM mouse model with dysfunctional leptin receptor (db/db) has been used in basic and translational studies of wound healing due to its systemic phenotypes (hyperphagia, hypometabolism, obesity, T2DM) and its notable delayed skin wound healing. However, a characterization of the temporal cellular dynamics of the db/db wound healing model has not been performed, nor has the model been systematically compared to human DFUs. We performed the first comprehensive single-cell, multi-omic analysis of dermal cells in diabetic (db/db) compared to non-diabetic (ND) mice across three time points ranging from the inflammatory to the delayed proliferative and resolution phases of healing. Single-cell transcriptomics were uniquely linked to their corresponding cells' surface protein expressions of cell-specific receptors, including immune cells (CD45) such as neutrophils (CD11b, Ly6G), monocytes/macrophages (CD11b, F4/80, CD11c, Ly6C) and T lymphocytes (CD3, CD4), and dermal cells such as endothelial cells (CD31) and fibroblasts (CD26, CD140a), and showed high concordance between protein cell markers and their gene expressions in major cell types. Differential multi-omic analyses characterized two neutrophil ( Ly6G , Ly6G ), three monocyte/macrophage (F4/80 CD11b , Ly6c CD11b , CD11c CD11b ) and three fibroblast ( CD26 , CD140a , CD26 ) subtypes showing dysregulated dynamics across the time course of healing in db/db vs ND mice. Notably, NETotic Ly6G neutrophils and phagocytic F4/80 CD11b macrophage subtypes were drastically up-regulated in diabetic wounds. Differential cell-cell communication analyses revealed striking differences in crosstalk dynamics between fibroblast, macrophage and neutrophil subtypes in the early phase of healing, and ligand-receptor interactome analyses identified CD44 as the hub of dysregulated immune cell interactions in diabetic wounds, implicating cell adhesion, migration and inflammatory pathways, especially those mediated by ICAM1. Inhibition of CD44 using blocking antibodies in primary macrophages from db/db mice and via intradermal injections in db/db mice significantly normalized the early wound immune dysfunction, in part by inhibiting ICAM1 and reversing the excessive neutrophil influx into diabetic wounds. A new integrated dataset of single-cell human chronic wound studies revealed similar CD44-mediated immune cell dysfunctions in diabetic vs non-diabetic foot ulcers, pointing to CD44 as a promising therapeutic target for T2DM-associated chronic wounds. - Source: PubMed
Publication date: 2026/04/29
Wietecha Mateusz SPang JingboKang MiyaHafedi AvinWalsdorf SamanthaKeiser ShalynMaienschein-Cline MarkKoh Timothy J - Pneumonia remains a leading cause of global mortality. Conventional diagnostic approaches frequently fail to distinguish microbial colonization from true infection in the lower respiratory tract, complicating clinical decision-making and contributing to antibiotic overuse. Improved diagnostic strategies are urgently needed. In this prospective, single-center study, deep sputum specimens were collected from patients with respiratory colonization (n = 17) and infectious pneumonia (n = 27) admitted to the neurosurgical ICU of Huashan Hospital. Metagenomic next-generation sequencing (mNGS) and metatranscriptomic profiling were performed to characterize both the pulmonary microbiota and the host immune response. These features were subsequently integrated to construct a diagnostic model. Microbial community profiling revealed reduced alpha diversity and enrichment of metabolically active pathogenic taxa in the infection group, consistent with a dysbiotic state permissive to invasion. In contrast, the colonization group demonstrated a more balanced microbial ecosystem. Transcriptomic analyses identified 2232 differentially expressed host genes between the two groups. The colonization group showed marked activation of the Wnt, MAPK, chemokine, and focal adhesion pathways, which are functionally implicated in epithelial barrier maintenance and early immune homeostasis. A multi-omics diagnostic model incorporating seven gene features (ANKRD52, ZC3HAV1L, SERPINE3, CDPF1, ZNF720, TAGLN3, and LRRC15) achieved a discrimination between colonization and infection (AUC = 0.951 in the training cohort; 0.875 in the validation set). By jointly analyzing the pulmonary microbiome and host transcriptome, this study provides insight into host-microbe interactions distinguishing colonization from infection and presents a predictive model with potential clinical relevance. - Source: PubMed
Publication date: 2026/04/03
Fu ZhangfanSun YuhanYao HaijunLiu QihuiZhang QiranHu JinZhou YangJiang NingAi JingwenJin JialinZhang Wenhong