Single-cell transcriptomic analysis reveals dynamic cellular processes in corneal epithelium during wound healing in cynomolgus monkeys
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ABSTRACT:
ORGANISM(S): Macaca fascicularis
PROVIDER: GSE276184 | GEO | 2024/09/20
REPOSITORIES: GEO
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Project description:Obesity and type 2 diabetes (T2D) remain major global healthcare challenges and developing therapeutics necessitate using nonhuman primate models. Here, we present proteomic analyses of all the major organs of cynomolgus monkeys with spontaneous obesity or T2D in comparison to healthy controls.
2023-06-23 | PXD036423 | Pride
Project description:Stem cells (SCs) are traditionally viewed as rare, slow-cycling cells that follow deterministic rules dictating their self-renewal or differentiation. It was several decades ago, when limbal epithelial SCs (LSCs) that regenerate the corneal epithelium were among the first sporadic, quiescent SCs ever discovered. However, LSC dynamics, heterogeneity and genetic signature are largely unknown. Moreover, recent accumulating evidence strongly suggested that epithelial SCs are actually abundant, frequently dividing cells that display stochastic behavior. In this work, we combined single-cell RNA sequencing and advanced quantitative lineage tracing for in-depth analysis of the murine limbal epithelium. The generated data provides an atlas of cell states of the entire corneal epithelial lineage and reveales the co-existence of two novel LSC populations that reside in separate and well-defined sub-compartments. In the “outer” limbus, we discovered a primitive widespread population of quiescent LSCs (qLSCs) that uniformly express Krt15/Gpha2/Ifitm3/Cd63 proteins that serve as SC reservoire and in boundary formation. In the “inner” peri-corneal limbus, we identified prevalent active LSCs (aLSCs) that express Krt15-GFP/Atf3/Mt1-2/Socs3 and maintain homeostasis. We propose that these SC populations are abundant, follow stochastic rules and neutral drift dynamics. Notably, we provide evidence that T cells serve as niche cells for qLSCs, regulating quiescence and wound response. Taken together, we propose that divergent regenerative strategies are tailored to properly support tissue specific physiological constraints.
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Project description:To identify plasma proteomics changes in primates aging and aging intervention, we performed DIA sequencing on blood plasma from the cynomolgus monkeys.
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Project description:Cynomolgus monkeys are well-established translational models for biomedical research and drug testing. To evaluate organ transcriptomes and gene expression variability in Cynomolgus monkeys, we used Customized NimbleGen Microarrays (Design ID: 120419_Cynomolgus_v5_TH_exp_HX12) for genome-wide gene expression profiling on 5 different tissues (heart, kidney, liver, lung, spleen) from 21 Cynomolgus monkeys. Cynomolgus monkey samples were derived from breeding centers located in the Philippines (3 females and 3 males), in Vietnam (2 females and 2 males), in China for animals from Mainland Southeast Asia (3 females), or in Mauritius (4 females and 4 males). Furthermore, genome-wide copy number variation was analyzed in tissue samples from the same animals using a custom NimbleGen 4.2 million probes comparative genomic hybridization (CGH) array to associate CNV genotypes with expression changes of proximal genes.
2016-02-24 | GSE76560 | GEO
Project description:Cynomolgus monkeys are well-established translational models for biomedical research and drug testing. Cynomolgus monkeys are outbred species and exhibit substantial levels of genetic variation which can affect the outcome and interpretation of biomedical studies. Copy number variations (CNVs) are a significant source of genetic diversity and a comprehensive understanding of the genomic impact of CNVs on phenotypic traits is limited. A custom 4.2 million probes comparative genomic hybridization (CGH) array (Design-ID: 120405_Cynomolgus5_CGH_UX1) has been designed on the basis of the Cynomolgus monkey genome (Ebeling et al. (2011) Genome Research; PMID: 21862625) to assess genome-wide copy number variation among Cynomolgus monkeys. Using Cynomolgus monkey specific NimbleGen CGH Microarrays we profiled the genomes of 21 Cynomolgus monkeys. Germline DNA from 21 Cynomolgus monkeys with different origin was tested against a Cynomolgus monkey reference. Cynomolus monkey samples were derived from breeding centers located in the Philippines (3 females and 3 males), in Vietnam (2 males and 2 females), in China for animals from Mainland Southeast Asia (3 females), or in Mauritius (4 females and 4 males). Furthermore genome-wide expression profiles were analyzed in 5 vitally important tissue samples (heart, kidney, liver, lung, spleen) from the same animals using a custom Cynomolgus monkey specific NimbleGen gene expression microarray (design ID: 120419_Cynomolgus_v5_TH_exp_HX12) to associate CNV genotypes with expression changes of proximal genes using a cis expression quantitative trait loci (cis-eQTL) mapping approach. Expression data have been deposited at the NCBI Gene Expression Omnibus (GEO) under accession numbers GSE76560. The array CGH results analyzed in this study are further described in Gschwind A.R. et al. (2016) "Diversity and regulatory impact of copy number variation in the primate Macaca fascicularis". under submission
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Project description:EXPERIMENT: The animal experiments were performed at Shin Nippon Biomedical Laboratories (SNBL), Ltd. (Kagoshima, Japan) in compliance with the Guideline for Animal Experimentation (1987), and in accordance with the Law Concerning the Protection and Control of Animals (1973) and the Standards Relating to the Care and Management of Experimental Animals (1980). This study was approved by the Institutional Animal Care and Use Committee of SNBL and performed in accordance with the ethics criteria contained in the bylaws of the SNBL committee. Each female monkey was paired with a male of proven fertility for one day between day 11 and day 15 of the menstrual cycle. Pregnant females, aged 5-8 years and weighing 2.84-3.76 kg on day 22 of gestation, were allocated randomly to two groups, each with three monkeys, and housed individually. The monkeys were orally dosed with (±)-thalidomide (Lot no. SDH7273/SDJ3347, Wako Pure Chemical Industries, Ltd., Osaka, Japan) at 0 or 20 mg/kg by oral intubation on day 26 of gestation, which was during the critical period for thalidomide-induced teratogenesis [Delahunt and Lassen, 1964; Hendrickx, 1973]. Dosage was adjusted to the body weight on day 22 of gestation and the drug was packed in a gelatin capsule. Control monkeys received the capsule only. ANIMAL MODEL: Macaca fascicularis INTERVAL: NON. PLATFORM: Proprietary Affymetrix NHP GeneChip® Array for Cynomolgus genome derived from Biogen Idec Keywords = Developmental Keywords = Monkeys Keywords = Thalidomide TFetal malformations and early embryonic gene expression response in cynomolgus monkeys maternally exposed to thalidomidechannel oligonucleotide (Affymetrix) platform.
2010-06-20 | E-GEOD-15542 | biostudies-arrayexpress
Project description:Transplantation of amniotic membrane-expanded limbal epithelium (AMLE) in place of donor tissue grafts results in significantly improved outcomes for patients suffering from severe limbal stem cell deficiency; however the reasons for such superior results are unclear. The purpose of this study was to identify transcriptional gene profiles specific to AMLE and donor central corneal epithelium (CE), which may contribute to the divergent clinical outcomes observed following transplant. Limbal fibroblasts which underlie the epithelium and secrete extracellular matrix proteins following injury/surgery were also profiled. Using cell culture, immunofluorescence, microarray gene expression profiling and qRT-PCR validation; this study aims to identify enriched biological processes and pathways which characterise AMLE and CE tissues. We hope the study outcomes will shed light onto the factors which contribute to provide the improved clinical outcomes associated with AMLE transplantation. Gene expression profiling of three central corneal buttons, three amniotic membrane-expanded limbal epithelial cultures and three limbal fibroblast cultures
2014-10-02 | E-GEOD-56421 | biostudies-arrayexpress
Project description:Cornea, the outermost transparent layer of the eye, is the first line of defense against external threats. Following injury, the wound healing response is crucial to corneal repair and regeneration, yet its underlying mechanism is poorly understood. Our study was designed to investigate the role of dsRNA and its regulatory network in corneal wound healing.
2022-02-05 | GSE191228 | GEO
Project description:Transplantation of ex vivo expanded limbal stem cells (LSC) is the main treatment for limbal stem cell deficiency though the clinical problem of donor tissues shortage. Recently, as the development of tissue engineering, embryonic stem cells (ESC) derived corneal epithelial-like cells (ESC-CEC) has become a new direction to this issue.Our group successfully induced ESC into corneal epithelial-like cells, and in the present study we explored various aspects of physiological properties of ESC-CEC. The experiment included three samples: hES, the human embryonic stem cell line H1, RA_SB, the corneal epithelial-like cells derived from hES by differentiation with RA and SB, epithelial_cell, the primary human limbal stem cells from cadaver eyes. hES, the human embryonic stem cell line H1, RA_SB, the corneal epithelial-like cells derived from hES by differentiation with RA and SB, epithelial_cell, the primary human limbal stem cells from cadaver eyes.
2015-06-24 | E-GEOD-70152 | biostudies-arrayexpress
Project description:RNA sequencing of lung tissue of cynomolgus monkeys
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