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PIEZO2 mechanoreceptor-expressing fibroblasts in keloids cause short-term recurrence after surgical resection

ABSTRACT: PIEZO2 mechanoreceptor-expressing fibroblasts in keloids cause short-term recurrence after surgical resection

PROVIDER: PRJNA1147694 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30223607_1.fastq.gz	Fastqsanger.gz
	SRR30223607_2.fastq.gz	Fastqsanger.gz
	SRR30223608_1.fastq.gz	Fastqsanger.gz
	SRR30223608_2.fastq.gz	Fastqsanger.gz
	SRR30223609_1.fastq.gz	Fastqsanger.gz

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PIEZO2 mechanoreceptor-expressing fibroblasts in keloids cause short-term recurrence after surgical resection

Project description:Keloids are characterized by persistent scar tissue growth that causes abnormal sensory perceptions due to mechanical stress. But the molecular dysfunction and disease-specific cells that fashion keloid pathophysiology are still not evident. Here, we found a distinct subpopulation of fibroblasts with enhanced expression of PIEZO2 in the dermal layer of keloid patients experiencing dysesthesia, including pain and pressure-tactile itch. The PIEZO2-expressing fibroblasts exhibited a keloid-typical phenotype marked by increased extracellular matrix production signaling and higher levels of collagens such as COL1A1, COL1A2, and COL3A1 compared with other fibroblasts. Notably, patients with higher PIEZO2 expression tend to experience keloid recurrence more quickly after keloidectomy (4/5 vs. 0/5, p = 0.047) than those with lower PIEZO2 expression. Thus, the PIEZO2-positive fibroblasts are indicative cells that most accurately reflect the keloid characteristics, suggesting the driving role for the persistent growth of Keloids.

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Fibroblasts expressing PIEZO2 mechanoreceptor in keloids possibly cause alloknesis and short-term recurrence after surgical resection [RNA-seq]

Project description:Keloids are scar tissue that can develop under tensile stress and manifest the tactile itch called alloknesis due to the heterogeneous course. But the molecular and cellular mechanisms underlying the pathology of keloid have been still unknown. Here, we found that unique fibroblast subpopulation that have dense-core granules with enhanced expression of PIEZO2 in the dermal layer of keloid tissue with alloknesis, a pressure-tactile itch. PIEZO2-expressed fibroblasts showed enhanced expression of COL1A1, COL1A2 and COL3A1. Gene expression profile analysis of fibrous disease tissues could distinguish the keloid cases by higher PIEZO2, which correlated with collagen COL1A1, COL1A2, and COL3A1 gene expression, not only from the keloid cases with lower PIEZO2 expression but also from the lymphedema cases where massive fibroblast proliferation appears. Notably, patients with the keloid accompanied by higher expression of PIEZO2 showed a significantly shorter time to recurrence after keloidectomy in patients with the keloids (4/5 vs. 0/5, p = 0.047). Thus, a unique subset of PIEZO2-positive fibroblasts may be involved in a keloid pathology and be a potent therapeutic target for the intractable keloids.

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Fibroblasts expressing PIEZO2 mechanoreceptor in keloids possibly cause alloknesis and short-term recurrence after surgical resection [scRNA-seq]

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Fibroblasts expressing PIEZO2 mechanoreceptor in keloids possibly cause alloknesis and short-term recurrence after surgical resection [scRNA-seq]

Project description:Fibroblasts expressing PIEZO2 mechanoreceptor in keloids possibly cause alloknesis and short-term recurrence after surgical resection [scRNA-seq]

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Fibroblasts expressing PIEZO2 mechanoreceptor in keloids possibly cause alloknesis and short-term recurrence after surgical resection [RNA-seq]

Project description:Fibroblasts expressing PIEZO2 mechanoreceptor in keloids possibly cause alloknesis and short-term recurrence after surgical resection [RNA-seq]

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A key role of PIEZO2 mechanosensitive ion channel in adipose sensory innervation [scRNA-seq]

Project description:Compared to the well-established functions of sympathetic innervation, the role of sensory afferents in adipose tissues remains less understood. Recent work revealed the anatomical and physiological significance of adipose sensory innervation; however, its molecular underpinning remains unclear. Here, using organ-targeted single-cell RNA sequencing, we identified the mechanoreceptor PIEZO2 as one of the most prevalent receptors in fat-innervating dorsal root ganglia (DRG) neurons. Selective PIEZO2 deletion in fat-innervating neurons led to molecular alternations in adipose tissue similar to DRG ablation. Conversely, a gain-of-function PIEZO2 mutant shifted the adipose phenotypes in the opposite direction. These results indicate that PIEZO2 plays a major role in the sensory regulation of adipose tissues. This discovery opens new avenues for exploring mechanosensation in organs not traditionally considered mechanically active, such as the adipose tissues, and therefore sheds light on the broader significance of mechanosensation in regulating organ function and homeostasis.

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A key role of PIEZO2 mechanosensitive ion channel in adipose sensory innervation [bulk RNA-seq]

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Molecular classification of meningioma predicts the response to surgical resection and adjuvant radiotherapy.

Project description:Molecular classification of meningioma predicts the response to surgical resection and adjuvant radiotherapy.

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