Single-cell analysis of endometriosis reveals a coordinated transcriptional programme driving immunotolerance and angiogenesis across eutopic and ectopic tissues

Nature Cell Biology, Год журнала: 2022, Номер 24(8), С. 1306 - 1318

Опубликована: Июль 21, 2022

Язык: Английский

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Human embryo implantation

Development, Год журнала: 2023, Номер 150(10)

Опубликована: Май 15, 2023

Embryo implantation in humans is interstitial, meaning the entire conceptus embeds endometrium before placental trophoblast invades beyond uterine mucosa into underlying inner myometrium. Once implanted, embryo survival pivots on transformation of an anti-inflammatory bed, termed decidua, under homeostatic control natural killer cells. Here, we examine evolutionary context and elaborate remodelling after conception humans. We also discuss interactions between decidualising that regulate interstitial determine fitness. Together, this Review highlights precarious but adaptable nature process.

Язык: Английский

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Endometrial Stem Cells: Orchestrating Dynamic Regeneration of Endometrium and Their Implications in Diverse Endometrial Disorders

International Journal of Biological Sciences, Год журнала: 2024, Номер 20(3), С. 864 - 879

Опубликована: Янв. 1, 2024

The human endometrium, a vital component of the uterus, undergoes dynamic changes during menstrual cycle to create receptive environment for embryo implantation. Its remarkable regenerative capacity can be attributed presence tissue-resident stem cell populations within endometrium. Despite variations in characteristics among different subtypes, endometrial cells exhibit notably robust self-renewal and ability differentiate into multiple lineages. This review offers comprehensive insight current literature recent advancements regarding roles various types regeneration endometrium cycle. In addition, emerging evidence suggests that dysfunction or depletion may play critical development progression disorders, such as endometriosis, uterine fibroids, adenomyosis, infertility, cancer. Therefore, we also highlight potential these diseases, including their accumulate genetic mutations express genes associated with diseases. Understanding properties disorders will shed light on therapeutic strategies managing conditions improving women's fertility outcomes.

Язык: Английский

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Time-series single-cell transcriptomic profiling of luteal-phase endometrium uncovers dynamic characteristics and its dysregulation in recurrent implantation failures

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 2, 2025

Язык: Английский

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Single-Cell Transcriptomics of Proliferative Phase Endometrium: Systems Analysis of Cell–Cell Communication Network Using CellChat

Frontiers in Cell and Developmental Biology, Год журнала: 2022, Номер 10

Опубликована: Июль 22, 2022

The endometrium thickness increases by which endometrial angiogenesis occurs in parallel with the rapid growth of during proliferative phase, is orchestrated complex cell-cell interactions and cytokine networks. However, intercellular communication has not been fully delineated. In present work, we studied interactome among cells human phase using single-cell transcriptomics. transcriptomes 33,240 primary were profiled at resolution. CellChat was used to infer assessing gene expression receptor-ligand pairs across cell types. total, nine types 88 functionally related signaling pathways found. Among them, factors angiogenic factor pathways, including EGF, FGF, IGF, PDGF, TGFb, VEGF, ANGPT, ANGPTL that are highly associated growth, further analyzed verified. results showed stromal proliferating represented interaction hubs a large number PDGF incoming signals, FGF outgoing signals. Endothelial exhibited plenty TGFb ANGPT Unciliated epithelial cells, ciliated macrophages substantial EGF Ciliated IGF Smooth muscle lots signals This study deconvoluted communications level predicted meaningful biological discoveries, deepened understanding cells.

Язык: Английский

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Stromal cell senescence contributes to impaired endometrial decidualization and defective interaction with trophoblast cells

Human Reproduction, Год журнала: 2022, Номер 37(7), С. 1505 - 1524

Опубликована: Май 6, 2022

Abstract STUDY QUESTION What are the consequences of endometrial stromal cell (EnSC) senescence for function? SUMMARY ANSWER Senescence EnSC contributes to impaired decidualization and interaction with trophoblast cells but application senomorphics diminishes adverse effects senescent on implantation. WHAT IS KNOWN ALREADY A prolonged highly disordered pro-inflammatory secretory profile EnSC, which resembles senescence-associated phenotype, is associated implantation failure. Furthermore, it has been suggested that failure may be increased during proliferative phase menstrual cycle. DESIGN, SIZE, DURATION Primary cultures were isolated from biopsies taken four patients without any complications planning undergo IVF. was induced by oxidative stress (1 h exposure 200 µM H2O2) followed 14 days culture some results confirmed in a replicative model (after 25 passages). The decidual reaction evaluated routine methods genetic tool previously designed us estimates integral response fluorescence reporter protein. Time-course RNA-sequencing control before performed using replicates each state. To extend our findings, we applied several publicly available datasets. vitro, choriocarcinoma line BeWo b30 used. reduce phenotype two classical applied—rapamycin metformin. PARTICIPANTS/MATERIALS, SETTING, METHODS used investigate an vitro spheroids derived cells. Co-culture models (2D 3D) explore effect neighbouring following assess function, RNA-sequencing, bioinformatic analysis, CRISPR/Cas9 genome editing, FACS, western blotting, RT–PCR, immunofluorescence, molecular cloning, lentiviral transduction ELISA. MAIN RESULTS AND THE ROLE OF CHANCE Premature could cause decidualization. Hormone-induced transformation negatively affected senescence. Bioinformatics revealed crucial disturbances affect embryo invasion, alter ‘meta-signature’ human receptivity, disturb emergence mature subpopulations, impair ligand–receptor trophoblasts modify architecture extracellular matrix. These predictions functionally validated model. Moreover, observed likely via altered secretome, caused ‘bystander’ quenching adjacent cells, reinforcing dysfunction compartment. Application reduced diminished LARGE SCALE DATA data this study GEO database (GEO identifier GSE160702). LIMITATIONS, REASONS FOR CAUTION present based only women. Further studies involving needed confirm findings. WIDER IMPLICATIONS FINDINGS presence within compartment endometrium risk-factor cycle promising strategy alleviate negative improve rates. FUNDING/COMPETING INTEREST(S) This funded Russian Science Foundation (# 19-74-10038). authors do not have competing interests declare.

Язык: Английский

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Decoding the endometrial niche of Asherman’s Syndrome at single-cell resolution

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Сен. 21, 2023

Asherman's Syndrome is characterized by intrauterine adhesions or scarring, which cause infertility, menstrual abnormalities, and recurrent pregnancy loss. The pathophysiology of this syndrome remains unknown, with treatment restricted to surgical removal has limited success. Here, we decode the endometrial cell niche analyzing data from over 200,000 cells single-cell RNA-sequencing in patients condition through vitro analyses patient-derived organoids. Our atlas highlights loss epithelium, alterations epithelial differentiation signaling pathways such as Wnt Notch, appearance characteristic epithelium expressing secretory leukocyte protease inhibitor during window implantation. We describe syndrome-associated cell-to-cell communication gene expression profiles that support a dysfunctional pro-fibrotic, pro-inflammatory, anti-angiogenic environment.

Язык: Английский

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Establishment of the fetal-maternal interface: developmental events in human implantation and placentation

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11

Опубликована: Май 17, 2023

Early pregnancy is a complex and well-orchestrated differentiation process that involves all the cellular elements of fetal-maternal interface. Aberrant trophoblast-decidual interactions can lead to miscarriage disorders occur later in pregnancy, including preeclampsia, intrauterine fetal growth restriction, preterm labor. A great deal research on regulation implantation placentation has been performed wide range species. However, there significant species variation regarding trophoblast as well decidual-specific gene expression regulation. Most relevant information obtained from studies using mouse models. comprehensive understanding physiology pathology human only recently because emerging advanced technologies. With derivation stem cells, 3D-organoid cultures, single-cell analyses differentiated cell type-specific transcript profiles functions were generated, each exhibited unique signature. Additionally, through integrative transcriptomic information, researchers uncover dysfunction embryonic placental cells peri-implantation embryos early pathological placenta. In fact, clinical utility trafficking applied for noninvasive prenatal diagnosis aneuploidies prediction complications. Furthermore, recent have proposed viable path toward development therapeutic strategies targeting placenta-enriched molecules diseases.

Язык: Английский

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Targeting CD301⁺ macrophages inhibits endometrial fibrosis and improves pregnancy outcome

EMBO Molecular Medicine, Год журнала: 2023, Номер 15(9)

Опубликована: Июль 31, 2023

Abstract Macrophages are a key and heterogeneous cell population involved in endometrial repair regeneration during the menstrual cycle, but their role development of intrauterine adhesion (IUA) sequential fibrosis remains unclear. Here, we reported that CD301 + macrophages were significantly increased showed most active interaction with profibrotic cells endometria IUA patients compared normal by single‐cell RNA sequencing, bulk experimental verification. Increasing promoted differentiation stromal into myofibroblasts resulted extracellular matrix accumulation, which destroyed physiological architecture tissue, drove fibrosis, ultimately led to female infertility or adverse pregnancy outcomes. Mechanistically, secreted GAS6 activate AXL/NF‐κB pathway, upregulating protein synthesis. Targeted deletion inhibition AXL Bemcentinib blunted pathology improved outcomes mice, supporting therapeutic potential targeting for treating fibrosis.

Язык: Английский

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Multi-omics-based mapping of decidualization resistance in patients with a history of severe preeclampsia

Nature Medicine, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Endometrial decidualization resistance (DR) is implicated in various gynecological and obstetric conditions. Here, using a multi-omic strategy, we unraveled the cellular molecular characteristics of DR patients who have suffered severe preeclampsia (sPE). Morphological analysis unveiled significant glandular anatomical abnormalities, confirmed histologically quantified by digitization hematoxylin eosin-stained tissue sections. Single-cell RNA sequencing (scRNA-seq) endometrial samples from with sPE (n = 11) controls 12) revealed sPE-associated shifts cell composition, manifesting as stromal mosaic state characterized proliferative cells (MMP11 SFRP4) alongside IGFBP1+ decidualized cells, concurrent epithelial mosaicism dearth epithelial–stromal transition associated decidualization. Cell–cell communication network mapping underscored aberrant crosstalk among specific types, implicating crucial pathways such endoglin, WNT SPP1. Spatial transcriptomics replication cohort validated DR-associated features. Laser capture microdissection/mass spectrometry second corroborated several scRNA-seq findings, notably absence to at pathway level, indicating disrupted response steroid hormones, particularly estrogens. These insights shed light on potential mechanisms underpinning pathogenesis context sPE. A multi-omics resistance, which conditions, history defects stroma, epithelium epithelial-to-stromal transition, findings separate cohort.

Язык: Английский

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