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Trigeminal nerve derived-substance P regulates biological characteristics of limbal stem cells through PI3K-AKT signaling pathway

ABSTRACT: Trigeminal nerve derived-substance P regulates biological characteristics of limbal stem cells through PI3K-AKT signaling pathway

PROVIDER: PRJNA879300 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21529514_1.fastq.gz	Fastqsanger.gz
	SRR21529514_2.fastq.gz	Fastqsanger.gz
	SRR21529515_1.fastq.gz	Fastqsanger.gz
	SRR21529515_2.fastq.gz	Fastqsanger.gz
	SRR21529516_1.fastq.gz	Fastqsanger.gz

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Trigeminal nerve derived-substance P regulates biological characteristics of limbal stem cells through PI3K-AKT signaling pathway

Project description:To investigate the function of Substance P- NK1R interaction in the regulation of limbal stem cells, we subconjunctivally injected NK1 receptor antagonist L-733,060 on mice. By RNA sequencing, we found that antagonist injection significantly downregulated PI3K-AKT signaling related genes level. Collectively, our work reveals that Substance P- NK1R interaction is a novel player in limbal stem cells regulation.

2023-05-17 | GSE213140 | GEO

Trigeminal nerve-derived substance P regulates limbal stem cells by the PI3K-AKT pathway.

Project description:Trigeminal nerve-derived substance P (SP), a widespread neuropeptide, is known to maintain the corneal epithelial homeostasis and promote the closure of wound healing. Using comprehensive in vivo and in vitro assays and RNA-sequencing analysis, we aimed to unveil the positive effects of SP on the biological characteristics of limbal stem cells (LSCs) and the underlying mechanism. SP enhanced the proliferation and stemness of LSCs in vitro. Correspondingly, it rescued corneal defects, corneal sensitivity, and the expression of LSC-positive markers in a neurotrophic keratopathy (NK) mouse model in vivo. Topical injection of a neurokinin-1 receptor (NK1R) antagonist caused similar pathological changes as in corneal denervated mice and attenuated LSC-positive markers levels. Mechanistically, we revealed that SP regulated LSCs functions by modulating the PI3K-AKT pathway. Our findings showed that the trigeminal nerve regulates LSCs by releasing SP, which may provide new insights into the regulation of LSCs' fate and stem cell therapy.

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In situ tissue profile of rat trigeminal nerve in trigeminal neuralgia using spatial transcriptome sequencing

Project description:Investigation on the transcriptome and intercellular communication of different cells of trigeminal nerve in trigeminal neuralgia rat by spatial transcriptome sequencing

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Limbal Niche

Project description:Comprehensive transcriptome analysis of four distinct human limbal compartments, including basal limbal crypts (BLCs), superficial limbal crypts (SLCs), cornea, and the supporting stroma, with the aid of laser capture microdissection and deep RNA sequencing.

2013-07-01 | E-MTAB-1498 | biostudies-arrayexpress

Limbal Niche

Project description:Limbal Niche

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Differentiation of human limbal-derived induced pluripotent stem cells into limbal-like epithelium

Project description:Limbal epithelial stem cell (LESC) deficiency represents a significant clinical problem especially in bilateral cases. Induced pluripotent stem cells (iPSC) may be a promising source of LESC, allowing standardized and continual propagation and banking. The objective of this study was to generate iPSC from human limbal epithelial cultures and differentiate them back into limbal epithelial cells using substrata mimicking the natural LESC niche. Using Yamanaka’s episomal vectors limbal-derived iPSC were reprogrammed from LESC cultured from donor corneoscleral rims and from human skin fibroblasts. A clone from limbal-derived iPSC expressed stemness markers, had a diploid karyotype, and produced teratomas in nude mice representing three germ layers. Compared to parental LESC, this clone had fewer specific gene methylation changes revealed using the Illumina Infinium Methylation 450k Beadchips than compared to skin fibroblasts. The expression of putative LESC markers was examined by quantitative RT-PCR and immunostaining in limbal-derived and fibroblast-derived iPSC cultured on denuded human amniotic membrane or denuded cornea. Limbal-derived iPSC had markedly stronger expression of PAX6, ABCG2, Np63, keratins 14, 15, 17, and N-cadherin than fibroblast-derived iPSC. On denuded corneas, limbal-derived iPSC showed the expression of differentiated corneal keratins 3 and 12. The data suggest that iPSC differentiation to a desired lineage may be facilitated by their generation from the same tissue. This may be related to preservation of parental tissue epigenetic methylation signatures in iPSC and use of biological substrata similar to the natural niche of parental cells. The data pave the way for generating transplantable LESC from limbal-derived iPSC. Bisulphite converted DNA from the 12 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

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Differentiation of human limbal-derived induced pluripotent stem cells into limbal-like epithelium

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ABCB5+ limbal epithelial stem cells inhibit developmental, but promote inflammatory (lymph)angiogenesis while preventing corneal inflammation

Project description:ABCB5 is marker for Limbal epithilal stem cells. A comparison between ABCB5+ versus ABCB5- cultured human limbal epithelial cells was carried out to evaluate the properties of the limbal stem cell ABCB5+ with a special focus on their role in inflammation and angiogenesis.

2023-10-24 | PXD041004 | Pride

In situ tissue profile of rat trigeminal nerve in trigeminal neuralgia using spatial transcriptome sequencing

Project description:In situ tissue profile of rat trigeminal nerve in trigeminal neuralgia using spatial transcriptome sequencing

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