WNT and inflammatory signaling distinguish human Fallopian tube epithelial cell populations

Rose, Ian; Bidarimath, Mallikarjun; Webster, Alex; Godwin, Andrew K.; Flesken‐Nikitin, Andrea; Nikitin, Alexander Yu.

doi:10.1101/2020.01.15.908293

Cited by 3 publications

(11 citation statements)

References 45 publications

(55 reference statements)

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“…4A). These GO terms are similar to previously published datasets from other mammals, including cows and humans, where vesicle-mediated transport, endocytosis, and exocytosis were among the main processes enriched in the posterior (Gonella-Diaza et al, 2017;Maillo et al, 2016;Rose et al, 2020). We confirmed this trend using qPCR for a transport ATPase (Atp1b1) and a solute carrier (Slc39a8); both were significantly enriched in the posterior (Fig.…”

Section: The Mouse Oviduct Displays Robust Transcriptional Patterningsupporting

confidence: 90%

Spatiotemporal transcriptional dynamics of the cycling mouse oviduct

Roberson

Battenhouse

Garge

et al. 2021

Preprint

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Female fertility in mammals requires iterative remodeling of the entire adult female reproductive tract across the menstrual/estrous cycle. However, while transcriptome dynamics across the estrous cycle have been reported in human and bovine models, no global analysis of gene expression across the estrous cycle has yet been reported for the mouse. Here, we examined the cellular composition and global transcriptional dynamics of the mouse oviduct along the anteroposterior axis and across the estrous cycle. We observed robust patterns of differential gene expression along the anteroposterior axis, but we found surprisingly few changes in gene expression across the estrous cycle. Notable gene expression differences along the anteroposterior axis included a surprising enrichment for genes related to embryonic development, such as Hox and Wnt genes. The relatively stable transcriptional dynamics across the estrous cycle differ markedly from other mammals, leading us to speculate that this is an evolutionarily derived state that may reflect the extremely rapid five-day mouse estrous cycle. This dataset fills a critical gap by providing an important genomic resource for a highly tractable genetic model of mammalian female reproduction.

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Section: The Mouse Oviduct Displays Robust Transcriptional Patterningsupporting

confidence: 90%

Spatiotemporal transcriptional dynamics of the cycling mouse oviduct

Roberson

Battenhouse

Garge

et al. 2021

Preprint

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Section: Resultsmentioning

confidence: 99%

“…Although definitive markers for FT stem/progenitor cells remain elusive, Rose et al found an Aldh+ subpopulation enriched for stem/progenitor-like cells (38), and Dinh et al have identified a progenitor-like subset with high expression of Thy1, Igfbp5, and Lgals1 (41). Moreover, Wnt and Notch pathways are reported to maintain FT stemness (35, 38, 42). To compare these candidate markers and pathways between small and expanded clones, we isolated them separately from MADM-wildtype mice using fluorescence-guided laser capture microdissection (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The high clonogenicity of some Pax8+ cells is reminiscent of stem/progenitor-like cells (34). Although definitive FT stem/progenitor cell markers are still lacking, several studies showed that these cells are within the Pax8+ subpopulation and are spatially enriched in the fimbrial (distal) portion of FTs (35)(36)(37)(38)(39). To assess whether the expanded clones show similar spatial preference as the FT stem/progenitor cells do, we stretched the FTs from MADMwildtype mice and performed whole-mount imaging to examine the location of expanded clones.…”

Section: Spatial and Molecular Characterizations Of Expanded Clones H...mentioning

confidence: 99%

“…However, recent data suggest the existence of discrete populations of Pax8+ secretory cells. Daniel et al showed that Pax8+ secretory cells present heterogeneous organoid-forming ability in vitro (18,19), and Hu et al identified multi-subsets of Pax8+ cells with sing-cell sequencing (20,21). Whether this newly revealed diversity of Pax8+ secretory cells also present a hirarchical cellular context, and thus differential susceptibility for cancer initiation is unknown, Here, we exploited a mouse genetic system called Mosaic Analysis with Double Markers (MADM) (22,23) to trace clonal progression of individual mutated Pax8+ FT cells to compare their tumorigenic susceptibility.…”

Section: Introductionmentioning

confidence: 99%

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Quantitative clonal analysis reveals vast heterogeneity among fallopian tube cells for ovarian cancer-initiation and progression

Zeng

Álvarez-Yela

Casarez

et al. 2022

Preprint

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Clonal dynamics of mutant cells during early carcinogenesis result from the intersection between genetic mutations and cell-intrinsic states, and foreshadow the trajectory for further transformation. While fallopian tube (FT) Pax8+ cells are one of the origin for high-grade serous ovarian cancer (HGSOC), their clonal dynamics upon oncogenic mutations remain unknown. Here we use a mouse genetic mosaic system called MADM (Mosaic Analysis with Double Markers) that can generate sporadic mutant cells unequivocally labeled with GFP to gain access to the premalignant stages of HGSOC. The sparseness of mutant cells generated by MADM enabled us to investigate the fate of individual tumor-initiating Pax8+ cells at the clonal level. Surprisingly, we observed a dichotomous progression kinetics among mutant clones: while the vast majority stalls immediately, a small proportion expands significantly. Clonal analysis with wildtype MADM mice revealed the same dichotomy among normal Pax8+ clones, suggesting that cell-intrinsic properties determine its initial expansion capacity. Furthermore, while wildtype clones cease to expand shortly after development, expanded mutant clones manifest divergent fates: some enter quiescence, others maintained high proliferative rate and continue to progress, indicating that oncogenic mutations exaggerate clonal expansion beyond cell-intrinsic potentials. Finally, intra-clonal fate mapping showed that progressive cells have a higher propensity to maintain Pax8+ fate, implying possible prolonged stemness within progressive clones. Taken together, our studies reveal that clonal expansion during tumor initiation of HGSOC seems to be be an oncogenic mutation-induced exaggeration of a small group of Pax8+ cells with intrinsically high expansion potential, and suggest that future early detection and cancer prevention studies should focus on these rare progressing clones.

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Establishment and characterisation of oviductal organoids from farm and companion animals

Lawson

Ghosh

Blanch

et al. 2022

Preprint

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Organoid technology has provided us with a unique opportunity to study early human development and decipher various steps involved in the pathogenesis of human diseases. The technology is already used in clinics to improve human patient outcomes. However, limited knowledge of the methodologies required to establish organoid culture systems in domestic animals has slowed the advancement and application of organoid technology in veterinary medicine. Here, we have developed a platform to grow organoids from animal tissue samples and characterized oviductal organoids from five domestic animal species. Organoids were grown progressively from single cells derived from the enzymatic digestion of freshly collected equine, bovine, feline, canine, and porcine oviducts. The addition of WNT, TGFB, BMP, Rock, and Notch signalling pathway activators or inhibitors in the culture medium suggested remarkable conservation of the molecular signals involved in oviductal epithelial development and differentiation across species. The gross morphology of organoids from all the domestic species was initially similar. However, some differences in size, complexity, and growth rate were observed and described. Well-defined and synchronised motile ciliated cells were observed in differentiated organoids in mature populations. Histopathologically, oviductal organoids mimicked their respective native tissue. In summary, we have developed a detailed cross-species comparison of oviductal organoid models, which will be valuable for advancing assisted reproductive technologies and fertility studies in these animal species in the future.

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WNT and inflammatory signaling distinguish human Fallopian tube epithelial cell populations

Cited by 3 publications

References 45 publications

Spatiotemporal transcriptional dynamics of the cycling mouse oviduct

Spatiotemporal transcriptional dynamics of the cycling mouse oviduct

Quantitative clonal analysis reveals vast heterogeneity among fallopian tube cells for ovarian cancer-initiation and progression

Establishment and characterisation of oviductal organoids from farm and companion animals

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