Genomic, transcriptomic and proteomic depiction of iPSC-derived smooth muscle cells as emerging cellular models for arterial diseases DOI Creative Commons
Lu Liu, Charlène Jouve, Joséphine Henry

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: May 1, 2022

Abstract Background Vascular smooth muscle cells (VSMCs) plasticity is a central mechanism in cardiovascular health and disease. We aimed at providing deep cellular phenotyping, epigenomic proteomic depiction of SMCs derived from induced pluripotent stem (iPSCs) evaluating their potential as models the context complex genetic arterial diseases. Methods differentiated 3 human iPSC lines using either RepSox (R-SMCs) or PDGF-BB TGF-β (TP-SMCs), during second half 24-days-long protocol. In addition to assays, we performed RNA-Seq assay for transposase accessible chromatin (ATAC)-Seq 6 time-points differentiation. The extracellular matrix content (matrisome) generated by iPSCs was analyzed mass spectrometry. Results Both differentiation protocols with positive expression SMC markers. TP-SMCs exhibited greater capacity proliferation, migration lower calcium release response contractile stimuli compared R-SMCs. data showed that genes involved function arteries were highly expressed R-SMCs primary SMCs. Matrisome analyses supported an overexpression proteins wound repair higher secretion basal membrane constituents Open regions significantly enriched variants associated coronary artery disease blood pressure, while only peripheral Conclusions Our study portrayed two presenting complementary phenotypes high relevance plasticity. combination genome-editing tools, our supports use these regulatory mechanisms risk loci several Graphical

Language: Английский

Functional heterogeneity of cancer-associated fibroblasts with distinct neoadjuvant immunotherapy plus chemotherapy response in esophageal squamous cell carcinoma DOI Creative Commons
Jun Jiang, Chao Xu, Donghui Han

et al.

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Sept. 27, 2024

Abstract Novel neoadjuvant immunotherapy combined with chemotherapy (neoICT) has improved outcomes for patients esophageal squamous-cell carcinoma (ESCC), but challenges persist in low response rates and therapy resistance. Little is known about the intra-tumoral heterogeneity ESCC tumor microenvironment (TME) that underlies differential responses to therapy. We applied single-cell RNA sequencing (scRNA-seq) profiling multiplexed immunofluorescence staining thoroughly decipher TME specimens from a anti-PD1 combination clinical trial. The cancer-associated fibroblasts (CAFs) population showed significant alteration abundance following Specifically, IL6 + CCL2 immunomodulatory CAFs novel CD248 mechanoresponsive subset exhibited increasing infiltration. Mechanistically, approached lined nest physically block infiltration of CD8 T cells drug delivery, while induced therapeutic resistance distinct IL-6 expression. Among treated neoICT, we observed prominent CAF-T cell interactions. In particular, NECTIN2-TIGIT ligand-receptor pair was enriched samples, TIGIT identified as major inhibitory checkpoint cells. Our findings demonstrate alterations constituent identify functional phenotypes associated unfavorable patients. This provides potential targets enhance ESCC.

Language: Английский

Citations

1
Astragaloside IV Inhibits Lung Injury and Fibrosis Induced by PM2.5 by Targeting RUNX1 Through miR-362-3p DOI
Hao Tian, Yan Zhang, Wei Li

et al.

Molecular Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 13, 2024

Language: Английский

Citations

1
Distinct human stem cell subpopulations drive adipogenesis and fibrosis in musculoskeletal injury DOI Open Access
Steven Garcia, Justin Lau, Agustin Diaz

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 29, 2023

Fibroadipogenic progenitors (FAPs) maintain healthy skeletal muscle in homeostasis but drive degeneration chronic injuries by promoting adipogenesis and fibrosis. To uncover how these stem cells switch from a pro-regenerative to pro-degenerative role we perform single-cell mRNA sequencing of human FAPs injured muscles across spectrum injury, focusing on rotator cuff tears. We identify multiple subpopulations with progenitor, adipogenic, or fibrogenic gene signatures. utilize full flow cytometry distinct FAP based highly multiplexed protein expression. Injury severity increases adipogenic commitment is driven the downregulation DLK1. Treatment both

Language: Английский

Citations

3
Mechanisms and targeted reversion/prevention of hepatic fibrosis caused by the non-hereditary toxicity of benzo(a)pyrene DOI

Xinru Du,

Ming Jin,

R.Y. Li

et al.

The Science of The Total Environment, Journal Year: 2023, Volume and Issue: 912, P. 169496 - 169496

Published: Dec. 21, 2023

Language: Английский

Citations

2
Neonatal hyperoxia induces sex-dependent pulmonary cellular and transcriptomic changes in an experimental mouse model of bronchopulmonary dysplasia DOI Open Access
Sheng Xia, Lisandra Vila Ellis, Konner Winkley

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: July 14, 2022

ABSTRACT Hyperoxia (HOX) disrupts lung development in mice and causes bronchopulmonary dysplasia (BPD) neonates. To investigate sex-dependent molecular cellular programming involved HOX, we surveyed the mouse using single cell RNA sequencing (scRNA-seq), validated our findings human neonatal cells vitro . HOX-induced inflammation alveolar type (AT) 2 gave rise to damage associated transient progenitors (DATP). It also induced a new subpopulation of AT1 with reduced expression growth factors normally secreted by cells, but increased mitochondrial gene expression. Female epithelial had less EMT pulmonary fibrosis signaling HOX. In endothelium, expansion Car4+ EC (Cap2) was seen HOX along an emergent Cap2 repressed VEGF signaling. This regenerative response females exposed Mesenchymal inflammatory signatures distal interstitial fibroblast subcluster characterized lipid biosynthesis transcriptomic signature resembling myofibroblasts. fibroblasts resembled scRNA-seq data. These suggest that exposure programs distinct sex-specific stem progenitor reparative responses underpin remodeling BPD.

Language: Английский

Citations

3
Deciphering the spatial organization of fibrotic microenvironment in silica particles-induced pulmonary fibrosis DOI

Liliang Yang,

Xinyan Wei,

Piaopiao Sun

et al.

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 478, P. 135540 - 135540

Published: Aug. 22, 2024

Language: Английский

Citations

0
Calcipotriol abrogates TGF-β1/pSmad3-mediated collagen 1 synthesis in pancreatic stellate cells by downregulating RUNX1 DOI Creative Commons

Meifang Zheng,

Hongyan Li,

Li Sun

et al.

Toxicology and Applied Pharmacology, Journal Year: 2024, Volume and Issue: 491, P. 117078 - 117078

Published: Aug. 28, 2024

RUNX1 with CBFβ functions as an activator or repressor of critical mediators regulating cellular function. The aims this study were to clarify the role on TGF-β1-induced COL1 synthesis and mechanism calcipotriol (Cal) antagonizing in PSCs. RT-qPCR Western Blot for determining mRNAs proteins COL1A1/1A2 rat PSC line (RP-2 cell). Luciferase activities driven by COL1A1 COL1A2 promoter, co-immunoprecipitation immunoblotting pSmad3/RUNX1 CBFβ/RUNX1, knockdown upregulation Smad3 used. production was regulated TGF-β1/pSmad3 signaling pathway RP-2 cells. formed a coactivator TGF-β1-treated cells regulate transcriptions under fashion pSmad3/RUNX1/CBFβ complex. However, Cal effectively abrogated levels transcripts downregulating hindering formation complexes. This suggests that may be promising antifibrotic target treatment chronic pancreatitis.

Language: Английский

Citations

0
scHiClassifier: a deep learning framework for cell type prediction by fusing multiple feature sets from single-cell Hi-C data DOI Creative Commons
Xiangfei Zhou, Hao Wu

Briefings in Bioinformatics, Journal Year: 2024, Volume and Issue: 26(1)

Published: Nov. 22, 2024

Abstract Single-cell high-throughput chromosome conformation capture (Hi-C) technology enables capturing chromosomal spatial structure information at the cellular level. However, to effectively investigate changes in across different cell types, there is a requisite for methods that can identify types utilizing single-cell Hi-C data. Current frameworks type prediction based on data are limited, often struggling with features interpretability and biological significance, lacking convincing robust classification performance validation. In this study, we propose four new feature sets contact matrix clear significance. Furthermore, develop novel deep learning framework named scHiClassifier multi-head self-attention encoder, 1D convolution fusion, which integrates from these predict accurately. Through comprehensive comparison experiments benchmark six datasets, demonstrate superior universality of framework. We further assess robustness through perturbation dropout experiments. Moreover, using all yields optimal performance, supported by comparisons set combinations. The effectiveness superiority multiple extraction proven unsupervised dimensionality reduction methods. Additionally, analyze importance chromosomes “SHapley Additive exPlanations” method. accuracy reliability enrichment analysis. source code freely available https://github.com/HaoWuLab-Bioinformatics/scHiClassifier.

Language: Английский

Citations

0
Identification and development of Tetra-ARMS PCR-based screening test for a genetic variant of OLA1 (Tyr254Cys) in the human failing heart DOI Creative Commons
Praveen Kumar Dubey, Shubham Dubey, Sarojini Singh

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 19, 2023

Abstract Obg-like ATPase 1 (OLA1) protein has GTP and ATP hydrolyzing activities is important for cellular growth survival. The human OLA1 gene maps on chromosome 2, at the locus 1q31, close to Titin (TTN) gene, which associated with familial dilated cardiomyopathy (DCM). In this study, we found that expression of was significantly downregulated in failing heart tissue (HF) as compared non-failing tissues (NF). Moreover, using Sanger sequencing method, characterized screened genetic mutations patients heart-failing non-failing. Among patients, a total 15 mutations, including two transversions, one substitution, indel, eleven transition gene. All were intronic except non-synonymous mutation, 5144A>G, resulting 254Tyr>Cys exon 8 Furthermore, haplotype analysis these revealed single nucleotide polymorphisms (SNPs) are linked each other, disease-specific haplotypes. Additionally, screen point developed cost-effective, rapid screening PCR test can differentiate between homozygous (AA GG) heterozygous (A/G) genotypes. Our results show be used tool cardiomyopathy. These findings have implications diagnosis treatment Figure

Language: Английский

Citations

1
Transcriptional factor RUNX1: A potential therapeutic target for fibrotic pulmonary disease DOI Open Access

JIA LIU,

FAPING WANG,

Bo Yuan

et al.

Biocell, Journal Year: 2023, Volume and Issue: 47(4), P. 697 - 705

Published: Jan. 1, 2023

Runt-related transcription factor-1 (RUNX1), also known as the core-binding factor alpha 2 subunit, is closely related to human leukemia. The functions of RUNX1 in modulating cell proliferation, differentiation, and survival multiple systems have been gradually discovered with emergence transgenic mice. a powerful implicated diverse signaling pathways cellular mechanisms that participate lung development pulmonary diseases. has recently identified target regulator fibrotic remodeling diseases, particularly kidney. However, role fibrosis unclear. Pulmonary characterized by obscure nosogenesis, limited therapy, poor prognosis. Moreover, population patients increasing. Thus, there an unmet need for therapeutic targets. In this review, we retrospectively discuss alteration mRNA expression RNA sequencing data lungs protein levels mouse fibrosis. Subsequently, focused on interaction between several involved Finally, review highlights potential slowing progression disease.

Language: Английский

Citations

0