A body map of super-enhancers and their function in pig DOI Creative Commons
Youbing Yang, Xinyue Li, Meng Zhu

et al.

Frontiers in Veterinary Science, Journal Year: 2023, Volume and Issue: 10

Published: Oct. 6, 2023

Introduction Super-enhancers (SEs) are clusters of enhancers that act synergistically to drive the high-level expression genes involved in cell identity and function. Although SEs have been extensively investigated humans mice, they not well characterized pigs. Methods Here, we identified 42,380 14 pig tissues using chromatin immunoprecipitation sequencing, statistics its overall situation, studied composition characteristics SE, explored influence on gene expression. Results We observed approximately 40% normal (NEs) form SEs. Compared NEs, found were more likely be enriched with an activated enhancer show functions. Interestingly, showed X chromosome depletion short interspersed nuclear element enrichment, implying play important role sex traits repeat evolution. Additionally, SE-associated exhibited higher levels stronger conservation than NE-associated genes. However, largest had those smallest SEs, indicating SE size may Moreover, a negative correlation between distance expression, proximity can affect activity. Gene ontology enrichment motif analysis revealed strong tissue-specific For example, CORO2B brain-specific shows phenylalanine hydroxylase liver-specific Discussion In this study, illustrated body map their functions pigs, providing information patterns This study serve as valuable resource regulatory comparative analyses scientific community provides theoretical reference for genetic control mechanisms

Language: Английский

The chromatin landscape of healthy and injured cell types in the human kidney DOI Creative Commons
Debora L. Gisch, Michelle Brennan, Blue B. Lake

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 10, 2024

There is a need to define regions of gene activation or repression that control human kidney cells in states health, injury, and repair understand the molecular pathogenesis disease design therapeutic strategies. Comprehensive integration expression with epigenetic features regulatory elements remains significant challenge. We measure dual single nucleus RNA chromatin accessibility, DNA methylation, H3K27ac, H3K4me1, H3K4me3, H3K27me3 histone modifications decipher landscape regulation reference adaptive injury states. establish spatially-anchored epigenomic atlas kidney's active, silent, accessible across genome. Using this atlas, we note distinct different epithelial cell types. A proximal tubule transcription factor network ELF3, KLF6, KLF10 regulates transition between health while thick ascending limb regulated by NR2F1. Further, combined perturbation distinguishes two tubular subtypes, one which manifested trajectory after knockout. This will serve as foundation facilitate targeted cell-specific therapeutics reprogramming networks.

Language: Английский

Citations

19
PKD1 and PKD2 mRNA cis-inhibition drives polycystic kidney disease progression DOI Creative Commons
Ronak Lakhia, Harini Ramalingam,

Chun-Mien Chang

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 15, 2022

Autosomal dominant polycystic kidney disease (ADPKD), among the most common human genetic conditions and a frequent etiology of failure, is primarily caused by heterozygous PKD1 mutations. Kidney cyst formation occurs when dosage falls below critical threshold. However, no framework exists to harness remaining allele or reverse decline. Here, we show that mRNAs produced noninactivated are repressed via their 3'-UTR miR-17 binding element. Eliminating this motif (Pkd1

Language: Английский

Citations

42
Mechanisms of Cyst Development in Polycystic Kidney Disease DOI Creative Commons
Jiahe Qiu, Gregory G. Germino, Luís F. Menezes

et al.

Advances in Kidney Disease and Health, Journal Year: 2023, Volume and Issue: 30(3), P. 209 - 219

Published: April 22, 2023

Language: Английский

Citations

11
Epigenetics in autosomal dominant polycystic kidney disease DOI
Zhipeng Yan, Feng Cao, Tingting Shao

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: 1871(3), P. 167652 - 167652

Published: Jan. 1, 2025

Language: Английский

Citations

0
Extracellular Vesicles From Dental Pulp Cells Promote Osteogenic Differentiation in Periodontal Ligament Cells DOI Open Access
Yingying Li, Fenglan Li, Haitao Liu

et al.

Journal of Periodontal Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

Periodontal osseous defects are mainly caused by periodontitis, which seriously affects the quality of patient life. Dental pulp cells (DpCs)-derived extracellular vesicles (EVs) can effectively promote tissue regeneration. Homeobox A9 (HOXA9) mRNA is abundant in EVs derived from DSCs, may be related to promoting alveolar bone regeneration, but specific mechanism unclear. We aimed elucidate through HOXA9 DPCs-derived impact osteogenic differentiation periodontal ligament (PDLCs). were isolated and characterized transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), western blot. Lipopolysaccharide (LPS) was employed induce inflammatory environment. Cell viability assessed CCK8 assay. Calcium deposition determined Alizarin red staining. H3K27ac enrichment FLI1 enhancer region interaction between C/EBPα, HOXA9, analyzed ChIP The 293T dual luciferase reporter gene promoted PDLC osteogenesis under LPS treatment increased expression PDLCs. knockdown DPCs reversed effect on differentiation. facilitating competitively binding with C/EBPα. Moreover, activating PI3K/AKT pathway upregulating FLI1. Our study identified a previously unknown that HOXA9/FLI1 signaling axis participates processes treat injury. research presents theoretical basis for using

Language: Английский

Citations

0
Sexually dimorphic renal expression ofKlothois directed by a kidney-specific distal enhancer responsive to HNF1b DOI Open Access
Jakub Jankowski, Hye‐Kyung Lee, Chengyu Liu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 4, 2024

Transcription enhancers are genomic sequences regulating common and tissue-specific genes their disruption can contribute to human disease development progression.

Language: Английский

Citations

2
Cross-Species Insights into Autosomal Dominant Polycystic Kidney Disease: Provide an Alternative View on Research Advancement DOI Open Access

Jianing Luo,

Yuan Zhang, Sakthidasan Jayaprakash

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5646 - 5646

Published: May 22, 2024

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a prevalent hereditary disorder that affects the kidneys, characterized by development of an excessive number fluid-filled cysts varying sizes in both kidneys. Along with progression ADPKD, these enlarged displace normal kidney tissue, often accompanied interstitial fibrosis and inflammation, significantly impair renal function, leading to end-stage disease. Currently, precise mechanisms underlying ADPKD remain elusive, definitive cure has yet be discovered. This review delineates epidemiology, pathological features, clinical diagnostics or ADPKD-like disease across human populations, as well companion animals other domesticated species. A light been shed on pivotal genes biological pathways essential for preventing managing which underscores importance cross-species research addressing this complex condition. Treatment options are currently limited Tolvaptan, dialysis, surgical excision large cysts. However, comparative studies different species hold promise unveiling novel insights therapeutic strategies combat

Language: Английский

Citations

2
Targeting the ADPKD methylome using nanoparticle-mediated combination therapy DOI Creative Commons
Annie Trinh, Yi Huang,

Hanjuan Shao

et al.

APL Bioengineering, Journal Year: 2023, Volume and Issue: 7(2)

Published: June 1, 2023

DNA methylation aberrancies are found in autosomal dominant polycystic kidney disease (ADPKD), which suggests the methylome to be a promising therapeutic target. However, impact of combining inhibitors (DNMTi) and ADPKD drugs treating on disease-associated patterns has not been fully explored. To test this, drugs, metformin tolvaptan (MT), were delivered combination with DNMTi 5-aza-2'-deoxycytidine (Aza) 2D or 3D cystic

Language: Английский

Citations

6
The chromatin landscape of healthy and injured cell types in the human kidney DOI Open Access
Debora L. Gisch, Michelle Brennan, Blue B. Lake

et al.

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

Published: June 10, 2023

There is a need to define regions of gene activation or repression that control human kidney cells in states health, injury, and repair understand the molecular pathogenesis disease design therapeutic strategies. However, comprehensive integration expression with epigenetic features regulatory elements remains significant challenge. We measured dual single nucleus RNA chromatin accessibility, DNA methylation, H3K27ac, H3K4me1, H3K4me3, H3K27me3 histone modifications decipher landscape regulation reference adaptive injury states. established spatially-anchored epigenomic atlas kidney's active, silent, accessible across genome. Using this atlas, we noted distinct different epithelial cell types. A proximal tubule transcription factor network

Language: Английский

Citations

4
Myocardin-Related Transcription Factor Mediates Epithelial Fibrogenesis in Polycystic Kidney Disease DOI Creative Commons

Zsuzsanna Lichner,

Mei Ding,

Tarang Khare

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(11), P. 984 - 984

Published: June 5, 2024

Polycystic kidney disease (PKD) is characterized by extensive cyst formation and progressive fibrosis. However, the molecular mechanisms whereby loss/loss-of-function of Polycystin 1 or 2 (PC1/2) provokes fibrosis are largely unknown. The small GTPase RhoA has been recently implicated in

Language: Английский

Citations

1