Decoding Asherman's Syndrome Cells

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Summary

In this study of Asherman's Syndrome, a condition characterized by intrauterine scarring leading to fertility challenges, researchers remain uncertain about its exact origins. By analyzing over 200,000 cells using single-cell RNA-sequencing from individuals with the syndrome and studying patient-derived endometrial organoids, they observed a decline in the endometrial epithelium and shifts in specific signaling pathways. Their findings also revealed disrupted cellular communication and genetic expressions, indicating an environment prone to increased scarring, inflammation, and impeded vascular growth.

Research Criteria

The study delves into the varied and intricate nature of endometrial cells, seeking clarity on the root causes behind Asherman's Syndrome-related issues, namely intrauterine adhesion formation and endometrial irregularities. The study uses single-cell RNA sequencing to analyze the human endometrium and endometrial organoid culture systems to delve deeper into cellular interactions and dysfunctions in endometrial pathologies.

Fig.1 Experimental design¹.

Sample Type

Human endometrium and endometrial organoids.

Result—Changes in the AS Endometrium Revealed by Single-Cell Analysis

In a meticulous exploration of Asherman's syndrome (AS) endometrium, researchers employed single-cell RNA sequencing to discern the nuanced cellular landscape of this condition, contrasting it with healthy controls. The study unveiled eighteen distinct cell types within the AS endometrial atlas, including epithelial cells, stromal fibroblasts, and various immune populations. Notably, a unique epithelial subpopulation, termed "AS epithelium," was identified, characterized by heightened stress-related gene expression. Through their studies, they discerned notable variations in cell population proportions when contrasting AS with secretory benchmarks. AS displayed a noticeable decline in both the epithelium and ciliated epithelium populations. However, specific immune cells experienced a surge in AS. Furthermore, differential gene expression profiles emerged, with the AS endometrium displaying downregulated secretory activity genes but upregulated pro-inflammatory genes. This comprehensive single-cell atlas offers invaluable insights into the cellular and transcriptomic intricacies of AS endometria, shedding light on the previously uncharted tissue context of AS devoid of intrauterine adhesions (IUAs).

Fig.2 Cartography of the human endometrium using single-cell RNA sequencing in Asherman's syndrome patients and healthy controls¹.

Result—Changes in the AS Endometrium Revealed by Single-Cell Analysis

In the intricate cellular milieu of the AS endometrium, aberrant intercellular communication emerges as a pivotal factor, deviating from the normative tissue homeostasis. The study delineates a pronounced disruption in the communication networks between epithelial and stromal cells, with a marked shift towards stromal self-stimulation, primarily through the synthesis of extracellular matrix components. Concurrently, immune cells exhibit heightened signaling interactions with the endothelium, indicative of both pro-inflammatory responses and augmented immune cell recruitment. This is further underscored by the enrichment of signaling pathways associated with cardinal immune processes. Moreover, within the window of implantation (WOI) context, there's a discernible decline in the communication probability of both canonical and non-canonical WNT pathways, potentially impeding luminal cell differentiation. This is accompanied by a diminished NOTCH pathway signaling, particularly in the JAG1-NOTCH2 ligand-receptor pair, resonating with the perturbed differentiation of glandular epithelium subtypes. The WOI-centric analysis further unveils compromised epithelial structural integrity, exacerbated by a pro-inflammatory milieu adjacent to the luminal epithelium. Collectively, these findings illuminate a profound dysfunction in cellular interactions in AS, culminating in a pro-fibrotic landscape, impaired epithelial differentiation, and heightened immune responses.

Fig.3 Cell-to-cell communication differs between Asherman's syndrome and control endometria¹.

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Single Cell RNA Sequencing Service

At Creative Biolabs, we understand that cell populations seldom exhibit homogeneity and synchronization in their attributes. Our comprehensive suite of services, spanning sample preparation, library construction, and data analysis, is meticulously designed to unveil the intricate tapestry of transcriptome diversity within heterogeneous samples. This holistic approach not only empowers your project with unparalleled flexibility but also accelerates its pace, ultimately elevating data precision to the zenith.

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At Creative Biolabs, our commitment lies in delivering exceptional single-cell RNA sequencing solutions to researchers and innovators worldwide. Leveraging state-of-the-art technology and profound expertise, we meticulously produce highly sensitive scRNA-seq data, facilitating in-depth exploration of genetic diversity and intricacies at the cellular level. We specialize in tailoring protocols and providing comprehensive services, always attuned to our clients' unique requirements and budgetary constraints, solidifying our position as the preferred partner in advancing scientific inquiry and driving groundbreaking discoveries.

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Reference

1. Santamaria, Xavier, et al. "Decoding the endometrial niche of Asherman's Syndrome at single-cell resolution." Nature Communications 14 (2023): 5444.