A molecular atlas of the human postmenopausal fallopian tube and ovary from single-cell RNA and ATAC sequencing

Lengyel, Ernst; Li, Yan; Weigert, Melanie; Zhu, Lisha; Eckart, Heather; Javellana, Melissa; Ackroyd, Sarah; Xiao, Jason; Olalekan, Susan; Glass, Dianne; Iyer, Shilpa; Krishnan, Rahul; Bilecz, Agnes; Lastra, Ricardo R.; Chen, Mengjie; Basu, Anindita

doi:10.1016/j.celrep.2022.111838

Cited by 15 publications

(27 citation statements)

References 54 publications

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“…While a simple risk score stratification system modeled after previous cancer classifications (eg, breast mass classification, Breast Imaging Reporting and Data System) is clinically desirable and could be easily adopted by nonspecialists, adnexal masses are heterogeneous. The normal ovary and fallopian tubes have a multiplicity of different cell types that can give rise to benign, borderline, and malignant tumors; the World Health Organization ovary classification lists more than 70 tumor types . Therefore, a personalized risk assessment that allows a more tailored approach may be better suited to adnexal mass evaluations.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Performance of Ultrasonography-Based Risk Models in Differentiating Between Benign and Malignant Ovarian Tumors in a US Cohort

et al. 2023

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ImportanceUltrasonography-based risk models can help nonexpert clinicians evaluate adnexal lesions and reduce surgical interventions for benign tumors. Yet, these models have limited uptake in the US, and studies comparing their diagnostic accuracy are lacking.ObjectiveTo evaluate, in a US cohort, the diagnostic performance of 3 ultrasonography-based risk models for differentiating between benign and malignant adnexal lesions: International Ovarian Tumor Analysis (IOTA) Simple Rules with inconclusive cases reclassified as malignant or reevaluated by an expert, IOTA Assessment of Different Neoplasias in the Adnexa (ADNEX), and Ovarian-Adnexal Reporting and Data System (O-RADS).Design, Setting, and ParticipantsThis retrospective diagnostic study was conducted at a single US academic medical center and included consecutive patients aged 18 to 89 years with adnexal masses that were managed surgically or conservatively between January 2017 and October 2022.ExposureEvaluation of adnexal lesions using the Simple Rules, ADNEX, and O-RADS.Main Outcomes and MeasuresThe main outcome was diagnostic performance, including area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios. Surgery or follow-up were reference standards. Secondary analyses evaluated the models’ performances stratified by menopause status and race.ResultsThe cohort included 511 female patients with a 15.9% malignant tumor prevalence (81 patients). Mean (SD) ages of patients with benign and malignant adnexal lesions were 44.1 (14.4) and 52.5 (15.2) years, respectively, and 200 (39.1%) were postmenopausal. In the ROC analysis, the AUCs for discriminative performance of the ADNEX and O-RADS models were 0.96 (95% CI, 0.93-0.98) and 0.92 (95% CI, 0.90-0.95), respectively. After converting the ADNEX continuous individualized risk into the discrete ordinal categories of O-RADS, the ADNEX performance was reduced to an AUC of 0.93 (95% CI, 0.90-0.96), which was similar to that for O-RADS. The Simple Rules combined with expert reevaluation had 93.8% sensitivity (95% CI, 86.2%-98.0%) and 91.9% specificity (95% CI, 88.9%-94.3%), and the Simple Rules combined with malignant classification had 93.8% sensitivity (95% CI, 86.2%-98.0%) and 88.1% specificity (95% CI, 84.7%-91.0%). At a 10% risk threshold, ADNEX had 91.4% sensitivity (95% CI, 83.0%-96.5%) and 86.3% specificity (95% CI, 82.7%-89.4%) and O-RADS had 98.8% sensitivity (95% CI, 93.3%-100%) and 74.4% specificity (95% CI, 70.0%-78.5%). The specificities of all models were significantly lower in the postmenopausal group. Subgroup analysis revealed high performances independent of race.Conclusions and RelevanceIn this diagnostic study of a US cohort, the Simple Rules, ADNEX, and O-RADS models performed well in differentiating between benign and malignant adnexal lesions; this outcome has been previously reported primarily in European populations. Risk stratification models can lead to more accurate and consistent evaluations of adnexal masses, especially when used by nonexpert clinicians, and may reduce unnecessary surgeries.

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Section: Discussionmentioning

confidence: 99%

Diagnostic Performance of Ultrasonography-Based Risk Models in Differentiating Between Benign and Malignant Ovarian Tumors in a US Cohort

et al. 2023

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“…We observed gene expression similarity and differences between epithelium and mesothelium, consistent with the notion that they are two lineages derived from the same progenitor. In human fallopian tubes (the oviduct), mesothelial cells were distinguished with two markers CALB2 and LRRN4 (83), which are different from the mesothelium marker Msln used in our mouse study.…”

Section: Extend Our Understanding Of the Less-studied Mesothelial Cellsmentioning

confidence: 93%

Single-cell transcriptomic profiling of the neonatal oviduct and uterus reveals new insights into upper Müllerian duct regionalization

Jia,

Zhao

2023

Preprint

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The upper Müllerian duct (MD) is patterned and specified into two morphologically and functionally distinct organs, the oviduct and uterus. It is known that this regionalization process is instructed by inductive signals from the adjacent mesenchyme. However, the interaction landscape between epithelium and mesenchyme during upper MD development remains largely unknown. Here, we performed single-cell transcriptomic profiling of mouse neonatal oviducts and uteri at the initiation of MD epithelial differentiation (postnatal day 3). We identified major cell types including epithelium, mesenchyme, pericytes, mesothelium, endothelium, and immune cells in both organs with established markers. Moreover, we uncovered region-specific epithelial and mesenchymal subpopulations and then deduced region-specific ligand-receptor pairs mediating mesenchymal-epithelial interactions along the craniocaudal axis. Unexpectedly, we discovered a mesenchymal subpopulation marked by neurofilaments with specific localizations at the mesometrial pole of both the neonatal oviduct and uterus. Lastly, we analyzed and revealed organ-specific signature genes of pericytes and mesothelial cells. Taken together, our study enriches our knowledge of upper Müllerian duct development, and provides a manageable list of potential genes, pathways, and region-specific cell subtypes for future functional studies.

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“…1,84 We observed gene expression similarity and differences between epithelium and mesothelium, consistent with the notion that they are two lineages derived from the same progenitor. In human fallopian tubes (the oviduct), mesothelial cells were distinguished with two markers CALB2 and LRRN4, 85 which are different from the mesothelium marker Msln used in our mouse study. MSLN was instead enriched in human oviductal secretory cells, [85][86][87] indicating species differences in mesothelium gene signatures.…”

Section: Extend Our Understanding Of the Less-studied Mesothelial Cellsmentioning

confidence: 95%

“…In human fallopian tubes (the oviduct), mesothelial cells were distinguished with two markers CALB2 and LRRN4, 85 which are different from the mesothelium marker Msln used in our mouse study. MSLN was instead enriched in human oviductal secretory cells, [85][86][87] indicating species differences in mesothelium gene signatures. We also observed gene expression differences between uterine and oviductal mesothelial cells.…”

Section: Extend Our Understanding Of the Less-studied Mesothelial Cellsmentioning

confidence: 95%

Single‐cell transcriptomic profiling of the neonatal oviduct and uterus reveals new insights into upper Müllerian duct regionalization

Jia,

Zhao

2024

The FASEB Journal

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The upper Müllerian duct (MD) is patterned and specified into two morphologically and functionally distinct organs, the oviduct and uterus. It is known that this regionalization process is instructed by inductive signals from the adjacent mesenchyme. However, the interaction landscape between epithelium and mesenchyme during upper MD development remains largely unknown. Here, we performed single‐cell transcriptomic profiling of mouse neonatal oviducts and uteri at the initiation of MD epithelial differentiation (postnatal day 3). We identified major cell types including epithelium, mesenchyme, pericytes, mesothelium, endothelium, and immune cells in both organs with established markers. Moreover, we uncovered region‐specific epithelial and mesenchymal subpopulations and then deduced region‐specific ligand‐receptor pairs mediating mesenchymal‐epithelial interactions along the craniocaudal axis. Unexpectedly, we discovered a mesenchymal subpopulation marked by neurofilaments with specific localizations at the mesometrial pole of both the neonatal oviduct and uterus. Lastly, we analyzed and revealed organ‐specific signature genes of pericytes and mesothelial cells. Taken together, our study enriches our knowledge of upper MD development, and provides a manageable list of potential genes, pathways, and region‐specific cell subtypes for future functional studies.

show abstract

A molecular atlas of the human postmenopausal fallopian tube and ovary from single-cell RNA and ATAC sequencing

Cited by 15 publications

References 54 publications

Diagnostic Performance of Ultrasonography-Based Risk Models in Differentiating Between Benign and Malignant Ovarian Tumors in a US Cohort

Diagnostic Performance of Ultrasonography-Based Risk Models in Differentiating Between Benign and Malignant Ovarian Tumors in a US Cohort

Single-cell transcriptomic profiling of the neonatal oviduct and uterus reveals new insights into upper Müllerian duct regionalization

Single‐cell transcriptomic profiling of the neonatal oviduct and uterus reveals new insights into upper Müllerian duct regionalization

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