The role of transcription factors in the pathogenesis and therapeutic targeting of vascular diseases DOI Creative Commons

Poyi Hu,

Yifan Du, Ying Xu

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 11

Published: April 30, 2024

Transcription factors (TFs) constitute an essential component of epigenetic regulation. They contribute to the progression vascular diseases by regulating gene expression in several diseases. Recently, numerous regulatory mechanisms related pathology, ranging from general TFs that are continuously activated histiocyte-specific under specific circumstances, have been studied. participate vascular-related epigenetically endothelial cells (VECs) and smooth muscle (VSMCs). The Krüppel-like family (KLF) TF is widely recognized as foremost regulator KLF11 prevents aneurysm inhibiting apoptosis VSMCs enhancing their contractile function. presence KLF4, another crucial member, suppresses atherosclerosis (AS) pulmonary hypertension attenuating formation VSMCs-derived foam cells, ameliorating dysfunction, inducing vasodilatory effects. However, mechanism underlying regulation has remained elusive. present study categorized involved shed light on potential pathogenesis diseases, provide novel insights into diagnosis treatment.

Language: Английский

Beyond genetics: driving cancer with the tumour microenvironment behind the wheel DOI
Shaopeng Yuan, Jorge Almagro, Elaine Fuchs

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(4), P. 274 - 286

Published: Feb. 12, 2024

Language: Английский

Citations

50
Vitamin A resolves lineage plasticity to orchestrate stem cell lineage choices DOI
Matthew Tierney, Lisa Polak, Yihao Yang

et al.

Science, Journal Year: 2024, Volume and Issue: 383(6687)

Published: March 7, 2024

Lineage plasticity-a state of dual fate expression-is required to release stem cells from their niche constraints and redirect them tissue compartments where they are most needed. In this work, we found that without resolving lineage plasticity, skin cannot effectively generate each in vitro nor regrow hair repair wounded epidermis vivo. A small-molecule screen unearthed retinoic acid as a critical regulator. Combining high-throughput approaches, cell culture, vivo mouse genetics, dissected its roles regeneration. We is made locally follicle niches, levels determine identity usage. Our findings have therapeutic implications for growth well chronic wounds cancers, plasticity unresolved.

Language: Английский

Citations

22
The activity of early-life gene regulatory elements is hijacked in aging through pervasive AP-1-linked chromatin opening DOI Creative Commons
Ralph Patrick,

Marina Naval-Sanchez,

Nikita Deshpande

et al.

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(8), P. 1858 - 1881.e23

Published: July 2, 2024

A mechanistic connection between aging and development is largely unexplored. Through profiling age-related chromatin transcriptional changes across 22 murine cell types, analyzed alongside previous mouse human organismal maturation datasets, we uncovered a transcription factor binding site (TFBS) signature common to both processes. Early-life candidate cis-regulatory elements (cCREs), progressively losing accessibility during aging, are enriched for cell-type identity TFBSs. Conversely, cCREs gaining throughout life have lower abundance of TFBSs but elevated activator protein 1 (AP-1) levels. We implicate TF redistribution toward these AP-1 TFBS-rich cCREs, in synergy with mild downregulation TFs, as driving early-life cCRE loss altering developmental metabolic gene expression. Such remodeling can be triggered by elevating or depleting repressive H3K27me3. propose that AP-1-linked opening drives disrupting thereby reprogramming transcriptome function, mechanism hijacked through ongoing opening.

Language: Английский

Citations

19
Pioneer factors: roles and their regulation in development DOI Creative Commons
Amandine Barral, Kenneth S. Zaret

Trends in Genetics, Journal Year: 2023, Volume and Issue: 40(2), P. 134 - 148

Published: Nov. 7, 2023

Language: Английский

Citations

40
ILC2 instructs neural stem and progenitor cells to potentiate neurorepair after stroke DOI
Gaoyu Liu,

Huachen Huang,

Ying Wang

et al.

Neuron, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

1
Epidermal stem cells: skin surveillance and clinical perspective DOI Creative Commons

Xin Tang,

Jiaqi Wang,

Jiaoling Chen

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 22, 2024

The skin epidermis is continually influenced by a myriad of internal and external elements. At its basal layer reside epidermal stem cells, which fuels renovation hair regeneration with powerful self-renewal ability, as well keeping diverse signals that direct their activity under surveillance quick response. importance cells in wound healing immune-related conditions has been increasingly recognized, potential for clinical applications attracting attention. In this review, we delve into recent advancements the various physiological psychological factors govern distinct cell populations, including stress, mechanical forces, chronic aging, circadian rhythm, providing an overview current methodological approaches. Furthermore, discuss pathogenic role disorders applications.

Language: Английский

Citations

6
Promoting epithelial regeneration in chemically induced acute lung injury through Sox9-positive alveolar type 2 epithelial cells DOI Creative Commons
Chao Cao,

Obulkasim Memete,

Yu Dun

et al.

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 23, 2025

Language: Английский

Citations

0
MLL4 regulates postnatal palate growth and midpalatal suture development DOI Creative Commons
Jung-Mi Lee,

Hunmin Jung,

Bruno de Paula Machado Pasqua

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 24, 2025

MLL4, also known as KMT2D, is a histone methyltransferase that acts an important epigenetic regulator in various organogenesis programs. Mutations the MLL4 gene are major cause of Kabuki syndrome, human developmental disorder involves craniofacial birth defects, including anomalies palate. This study aimed to investigate role and underlying mechanisms development growth We generated novel conditional knockout (cKO) mouse model with tissue-specific deletion Mll4 palatal mesenchyme. Using micro-computed tomography (CT), histological analysis, cell mechanism assays, expression profiling, we examined palate -cKO mice. Gross examination at adult stages revealed mild midfacial hypoplasia midline defects mice, widened midpalatal suture disrupted rugae pattern. Micro-CT-based time-course skeletal analysis during postnatal palatogenesis through adulthood demonstrated transverse deficit overall width Whole-mount staining perinatal identified mice emerged early 1 day prior birth, presenting suture, accompanied by increased apoptosis Genome-wide mRNA tissue essential for timely cartilage genes, such Col2a1 Acan , birth. Immunofluorescence osteochondral differentiation markers marked decrease chondrogenic marker COL2A1, while osteogenic RUNX2 remained unchanged, suture. Additionally, SOX9, master chondrogenesis, exhibited significant protein expression. Indeed, retardation Taken together, our results demonstrate orchestrating key cellular molecular events ensure proper growth.

Language: Английский

Citations

0
Molecular mechanisms altering cell identity in cancer DOI
Alessio Zippo, Sven Beyes

Oncogene, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Language: Английский

Citations

0
Dissection of Gαs and Hedgehog signaling crosstalk reveals therapeutic opportunities to target adenosine receptor 2b in Hedgehog-dependent tumors DOI Creative Commons
Sarah Krantz,

Brad Bell,

Katherine Lund

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Basal cell carcinoma (BCC), the most common human cancer, is driven by hyperactivation of Hedgehog Smoothened (SMO) and GLI transcription. Gαs protein kinase A (PKA) negatively regulate signaling, offering an alternative BCC development treatment pathway. Here, using histology alongside bulk single-cell RNA sequencing, we find that mouse BCC-like tumors originate from pathway inactivation are strikingly similar to those canonical SMO. Interestingly, mutations reduce PKA activity present in BCC. Tumors independent regulators SMO GPR161, establishing them as SMO-independent oncogenic signaling model. Finally, demonstrate activation Gαs-coupled adenosine 2B receptor counteracts SMO, reducing tumor formation a potential therapeutic strategy for

Language: Английский

Citations

0