Mapping the temporal and spatial dynamics of the human endometrium<i>in vivo</i>and<i>in vitro</i>

García-Alonso, Luz; Handfield, Louis-François; Roberts, Kenny; Νικολακοπούλου, Κωνσταντίνα; Fernando, Ridma C.; Gardner, Lucy; Woodhams, Ben; Arutyunyan, Anna; Polański, Krzysztof; Hoo, Regina; Sancho-Serra, Carmen; Li, Tong; Kwakwa, Kwasi; Tuck, Elizabeth; Kleshchevnikov, Vitalii; Tarkowska, Aleksandra; Porter, Tarryn; Mazzeo, Cecilia Icoresi; Dongen, Stijn van; Dąbrowska, Monika; Vaskivskyi, Vasyl; Mahbubani, Krishna T.; Park, Jong-eun; Jimenez-Liñan, Mercedes; Campos, Lia S.; Kiselev, Vladimir Yu; Lindskog, Cecilia; Ayuk, Paul; Prigmore, Elena; Stratton, Michael R.; Saeb‐Parsy, Kourosh; Moffett, Ashley; Moore, Luiza; Bayraktar, Ömer; Teichmann, Sarah A.; Turco, Margherita Y.; Vento‐Tormo, Roser

doi:10.1101/2021.01.02.425073

Cited by 30 publications

(49 citation statements)

References 41 publications

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“…Another example is confining CCC inference to cells that are expected to be in close contact, e.g. according to co-localizing cells in visium spots to reduce false positive interactions 25 . In a similar way, 10x Visium data can be used to identify cell types that are known to be co-located in visium spots, and are hence in close contact.…”

Section: Associations Between CCC Activity and Spatial-adjacencymentioning

confidence: 99%

Comparison of Resources and Methods to infer Cell-Cell Communication from Single-cell RNA Data

Dimitrov

Türei

Boys

et al. 2021

Preprint

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The growing availability of single-cell data has sparked an increased interest in the inference of cell-cell communication from this data. Many tools have been developed for this purpose. Each of them consists of a resource of intercellular interactions prior knowledge and a method to predict potential cell-cell communication events. Yet the impact of the choice of resource and method on the resulting predictions is largely unknown. To shed light on this, we created a framework, available at https://github.com/saezlab/ligrec_decoupler, to facilitate a comparative assessment of methods for inferring cell-cell communication from single cell transcriptomics data and then compared 15 resources and 6 methods. We found few unique interactions and a varying degree of overlap among the resources, and observed uneven coverage in terms of pathways and biological categories. We analysed a colorectal cancer single cell RNA-Seq dataset using all possible combinations of methods and resources. We found major differences among the highest ranked intercellular interactions inferred by each method even when using the same resources. The varying predictions lead to fundamentally different biological interpretations, highlighting the need to benchmark resources and methods.

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Section: Associations Between CCC Activity and Spatial-adjacencymentioning

confidence: 99%

Comparison of Resources and Methods to infer Cell-Cell Communication from Single-cell RNA Data

Dimitrov

Türei

Boys

et al. 2021

Preprint

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“…To retrieve interactions between supporting and other cell populations identified in our gonadal samples, we used an updated version of our CellPhoneDB 76,109 approach described in 27 . In short, we retrieved the interacting pairs of ligands and receptors meeting the following requirements: 1) all the protein members were expressed in at least 10% of the cell type under consideration; and 2) at least one of the protein members in the ligand or the receptor is a differentially expressed gene, with an adjusted p-value below 0.01 and a log2 fold change above 0.2.…”

Section: Cellphonedb and Cellsignmentioning

confidence: 99%

“…Coupled analysis of single-cell and spatial transcriptomic atlases of tissues have laid the groundwork to understanding human development 23,24 , mapping disease 25,26 and engineering organoids 27,28 . In addition, emerging studies of chromatin accessibility are revealing the first regulatory networks that have the potential to fine-map active transcription factors (TFs) during cell specification and associate genetic variants with cell type specificity [29][30][31] .…”

mentioning

confidence: 99%

Single-cell roadmap of human gonadal development

Vento‐Tormo¹,

García-Alonso²,

Lorenzi³

et al. 2021

Preprint

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Gonadal development is a complex process that involves sex determination followed by divergent maturation into ovaries or testes. Historically, limited tissue accessibility and lack of reliable in vitro models have impeded our understanding of human gonadogenesis, despite its importance in gonadal pathologies and infertility. Here, we generated a comprehensive map of first- and second-trimester gonadal development using a combination of single-cell and spatial transcriptomics, chromatin accessibility assays and imaging. Using this approach, we identified novel transcription factors and cell states in human germ and supporting cell lineages. We compared them with other mammalian species and found primate-specific regulatory programmes. Our data identified cell context–specific interactions shaping sex specification and development of human germ cells. We defined a novel bipotent progenitor cell (LGR5+, TSPAN8+) in late embryos that can differentiate into early Sertoli in males or pre-granulosa cells in females. In fetal ovaries, we defined two subsets of pre-granulosa cells supporting germ-cell differentiation and distributed across the cortico-medullary axis. We also found a subset of developing granulosa cells appearing during the second trimester of pregnancy that is involved in follicular assembly. In fetal testes, we defined a novel supporting population (sPAX8 cells) located at the poles of the developing testis cords. We also found two tissue-resident myeloid populations that we named microglia-like and SIGLEC15+ fetal testicular macrophages. This study provides an unprecedented spatiotemporal map of human gonadal differentiation that can be utilised as a blueprint for in vitro gametogenesis.

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“…Organoids are more expensive and labour intensive than 2D cell lines but the technique is relatively simple and can be easily adopted by other labs. As we move forward with these tools, it is imperative that we also continue to address issues including reproducibility and thorough comparisons with tissues to benchmark and improve the organoid models [120,236]. Furthermore, interdisciplinary approaches such as bioengineering to incorporate multiple cell types will help further develop these models.…”

Section: Discussionmentioning

confidence: 99%

Organoids of the female reproductive tract

Chumduri

Turco

2021

J Mol Med

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Healthy functioning of the female reproductive tract (FRT) depends on balanced and dynamic regulation by hormones during the menstrual cycle, pregnancy and childbirth. The mucosal epithelial lining of different regions of the FRT—ovaries, fallopian tubes, uterus, cervix and vagina—facilitates the selective transport of gametes and successful transfer of the zygote to the uterus where it implants and pregnancy takes place. It also prevents pathogen entry. Recent developments in three-dimensional (3D) organoid systems from the FRT now provide crucial experimental models that recapitulate the cellular heterogeneity and physiological, anatomical and functional properties of the organ in vitro. In this review, we summarise the state of the art on organoids generated from different regions of the FRT. We discuss the potential applications of these powerful in vitro models to study normal physiology, fertility, infections, diseases, drug discovery and personalised medicine.

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Mapping the temporal and spatial dynamics of the human endometriumin vivoandin vitro

Cited by 30 publications

References 41 publications

Comparison of Resources and Methods to infer Cell-Cell Communication from Single-cell RNA Data

Comparison of Resources and Methods to infer Cell-Cell Communication from Single-cell RNA Data

Single-cell roadmap of human gonadal development

Organoids of the female reproductive tract

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