Nucleus-localized S100A9 triggers senescence of human amnion fibroblasts as a heterochromatin buster at parturition - CUT&Tag
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ABSTRACT:
PROVIDER: PRJNA1214795 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32097058_1.fastq.gz | Fastqsanger.gz | |||
| SRR32097058_2.fastq.gz | Fastqsanger.gz | |||
| SRR32097059_1.fastq.gz | Fastqsanger.gz | |||
| SRR32097059_2.fastq.gz | Fastqsanger.gz |
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Project description:Aging in the amnion is considered to trigger and intensify inflammation for the initiation of labor. However, the inducers of amnion cell senescence await to be identified. Here, we unexpectedly observe that S100A9, a classical cytokines, also localizes in the nucleus of human amnion fibroblasts (hAFs), and reveal that nucleus-localized S100A9 (nS100A9) abundance in hAFs increases at parturition and that nS100A9 triggers hAFs senescence. Mechanistically, nS100A9 interacts with heterochromatin proteins, preventing them from binding and maintaining condensed heterochromatin, resulting in heterochromatin erosion, LINE1 de-repression, and type I interferon response activation via the cGAS-STING pathway. Moreover, we demonstrate that dephosphorylation of S100A9 at Thr 113 is required for its nuclear translocation. Mouse studies show that intra-amniotic injection of nS100A9 induces preterm birth along with LINE1 activation, which is blocked by reverse-transcriptase inhibitor. Together, these findings highlight a novel role for S100A9 as a heterochromatin buster that triggers hAFs aging at parturition.
2025-06-16 | GSE273966 | GEO
Project description:Aging in the amnion is considered to trigger and intensify inflammation for the initiation of labor. However, the inducers of amnion cell senescence await to be identified. Here, we unexpectedly observe that S100A9, a classical cytokines, also localizes in the nucleus of human amnion fibroblasts (hAFs), and reveal that nucleus-localized S100A9 (nS100A9) abundance in hAFs increases at parturition and that nS100A9 triggers hAFs senescence. Mechanistically, nS100A9 interacts with heterochromatin proteins, preventing them from binding and maintaining condensed heterochromatin, resulting in heterochromatin erosion, LINE1 de-repression, and type I interferon response activation via the cGAS-STING pathway. Moreover, we demonstrate that dephosphorylation of S100A9 at Thr 113 is required for its nuclear translocation. Mouse studies show that intra-amniotic injection of nS100A9 induces preterm birth along with LINE1 activation, which is blocked by reverse-transcriptase inhibitor. Together, these findings highlight a novel role for S100A9 as a heterochromatin buster that triggers hAFs aging at parturition.
2025-06-16 | GSE287835 | GEO
Project description:Nucleus-localized S100A9 triggers senescence of human amnion fibroblasts as a heterochromatin buster at parturition
| PRJNA1144373 | ENA
Project description:We investigated a potential role for SP-A in human pregnancy and parturition by examining SP-A expression patterns in amniotic fluid and the amnion
2010-04-12 | E-TABM-741 | biostudies-arrayexpress
Project description:Amnion-derived prostaglandin E2 (PGE2) and cortisol are key to labor onset. Identification of the common transcription factor driving the expression of both cyclooxygenase-2 (COX-2) and 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), the key enzymes in their production, may hold the key to the treatment of pre- and post-term labor. Here, we have found that the CCAAT enhancer binding protein δ (C/EBPδ) is such a transcription factor which underlies the feed-forward induction of COX-2 and 11β-HSD1 expression by their own products PGE2 and cortisol in human amnion fibroblasts so that their production would be ensured in the amnion for the onset of labor. Moreover, the abundance of C/EBPδ in amnion increases along with COX-2 and 11β-HSD1 at term and further increases at parturition. Knockout of C/EBPδ in mice delays the onset of labor further supporting the concept. In conclusion, C/EBPδ may serve as a novel pharmaceutical target in the amnion for treatment of pre- and post-term labor.
2021-07-15 | GSE166320 | GEO
Project description:Amnion-derived prostaglandin E2 (PGE2) and cortisol are key to labor onset. Identification of the common transcription factor driving the expression of both cyclooxygenase-2 (COX-2) and 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), the key enzymes in their production, may hold the key to the treatment of pre- and post-term labor. Here, we have found that the CCAAT enhancer binding protein δ (C/EBPδ)is such a transcription factor which underlies the feed-forward induction of COX-2 and 11β-HSD1 expression by their own products PGE2 and cortisol in human amnion fibroblasts so that their production would be ensured in the amnion for the onset of labor. Moreover, the abundance of C/EBPδin amnion increases along with COX-2 and 11β-HSD1 at term and further increases at parturition. Knockout of C/EBPδ in mice delays the onset of labor further supporting the concept. In conclusion, C/EBPδmay serve as a novel pharmaceutical target in the amnion for treatment of pre- and post-term labor.
2021-07-15 | GSE166454 | GEO
Project description:Amnion-derived prostaglandin E2 (PGE2) and cortisol are key to labor onset. Identification of the common transcription factor driving the expression of both cyclooxygenase-2 (COX-2) and 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), the key enzymes in their production, may hold the key to the treatment of pre- and post-term labor. Here, we have found that the CCAAT enhancer binding protein δ (C/EBPδ) is such a transcription factor which underlies the feed-forward induction of COX-2 and 11β-HSD1 expression by their own products PGE2 and cortisol in human amnion fibroblasts so that their production would be ensured in the amnion for the onset of labor. Moreover, the abundance of C/EBPδ in amnion increases along with COX-2 and 11β-HSD1 at term and further increases at parturition. Knockout of C/EBPδ in mice delays the onset of labor further supporting the concept. In conclusion, C/EBPδ may serve as a novel pharmaceutical target in the amnion for treatment of pre- and post-term labor.
2021-07-15 | GSE166453 | GEO
Project description:Amnion is a vital structure for human parturition, and it is anatomically compartmentalized into the placental amnion and the reflected amnion. microRNA expression was profiled to determine the expression pattern and its significance in the placental amnion and the reflected amnion in association with spontaneous labor at term.
2011-09-01 | GSE27441 | GEO
Project description:Amnion is a vital structure for human parturition, and it is anatomically compartmentalized into the placental amnion and the reflected amnion. microRNA expression was profiled to determine the expression pattern and its significance in the placental amnion and the reflected amnion in association with spontaneous labor at term. placental and reflected amnion tissue from two groups of women (term in labor and term no labor)
2011-08-31 | E-GEOD-27441 | biostudies-arrayexpress
Project description:The process of parturition involves the complex interplay of factors that changes the excitability and contractile activity of the uterus. We have compared the relative gene expression profile of myometrium from rats before parturition (21 days pregnant) and during delivery using high-density DNA microarray. Of 8740 sequences available in the array a total of 3782 were detected as present. From the sequences that were significantly altered, 59 genes were upregulated and 82 genes were downregulated. We were able to detect changes in genes described to have altered expression level at term including connexin 43 and 26, cyclo-oxygenase 2 and oxytocin receptor as well as novel genes that have been not previously associated with parturition. Quantitative real time PCR on selected genes further confirmed the microarray data. Here we report for the first time that aquaporin5 (AQP5), a member of aquaporin (AQP) water channel family, was dramatically downregulated during parturition (~100 fold by microarray and ~50 fold by Real Time PCR). The emerging profile highlights biochemical cascades occurring in a period of about 36 hours that triggers parturition and the initiation of myometrium reverse remodeling after partum. The microarray analysis uncovered genes that were previously suspected to play a role in parturition. This regulation involves genes from immune/inflammatory response, steroid/lipids metabolism, calcium homeostasis, cell volume regulation, cell signaling, cell division, and tissue remodeling, suggesting the presence of multiple and redundant mechanisms altered in the process of birth. Experiment Overall Design: Uteri were dissected from late pregnant rats (21 days, LP) (three individuals, two replicates of sample 1) and rats during labor (DL) after the expulsion of the second pup (three individuals, two replicates of sample 1). After dissection, uteri were placed immediately in cold Ca2+-free PBS buffer and peripheral large blood vessels, external surrounding connective tissue and placenta were removed. The endometrium superficial layer was separated by gentle scraping. The myometrium was weighted, finely minced and homogenized with a polytron (Polytron PT3000, Brinkmann, Switzerland).
2008-10-25 | E-GEOD-12799 | biostudies-arrayexpress