Single-cell sequencing of neonatal uterus reveals an Misr2+ endometrial progenitor indispensable for fertility

Saatcioglu, Hatice D.; Kano, Mariko; Horn, Heiko; Zhang, Lihua; Samore, Wesley; Nagykery, Nicholas; Meinsohn, Marie Charlotte; Hyun, Minsuk; Suliman, Rana; Poulo, Joy; Hsu, Jennifer Y.J.; Sacha, Caitlin R.; Wang, Dan; Gao, Guangping; Lage, Kasper; Oliva, Esther; Sabatini, Mary E.; Donahoe, Patricia K.; Pépin, David

doi:10.7554/elife.46349

Cited by 43 publications

(59 citation statements)

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“… 28 Placentas from participants with SARS-CoV-2 infection were tested for placental infection using RNA in situ hybridization, as previously described. 29 , 30 A SARS-CoV-2 –positive lung section and known SARS-CoV-2–positive placental section 31 were used as positive controls (eFigure 1 in the Supplement ). A subset of 7 cases from patients who were mildly or severely ill were additionally examined for expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) and the spike transmembrane serine protease 2 (TMPRSS2), which is required for viral cell entry, 32 by immunohistochemistry.…”

Section: Methodsmentioning

confidence: 99%

Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic

et al. 2020

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Key Points Question What key biological characteristics of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and placental function and pathology have implications for vertical transmission and neonatal protection? Findings In this prospective cohort study including 127 pregnancies, there was no maternal viremia, placental infection, or vertical transmission of SARS-CoV-2. Compromised transplacental transfer of anti–SARS-CoV-2 antibodies with robust transfer of influenza-specific immunity and nonoverlapping placental expression of SARS-CoV-2 receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 were noted. Meaning These findings suggest that, although low rates of maternal viremia and patterns of placental SARS-CoV-2 receptor distribution may underlie the rarity of vertical transmission, reduced transplacental transfer of anti–SARS-CoV-2 antibodies may leave neonates at risk for infection.

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Section: Methodsmentioning

confidence: 99%

Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic

et al. 2020

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“…reported the role that endometriosis played in oocytes from endometriotic ovaries by using scRNA-seq technology to calculate the global transcriptome behaviour [ 19 ]. Evidence from Saatcioglu et al proposed that Misr2 + cells could affect uterine hypoplasia and cause complete infertility through scRNA-seq [ 20 ]. Therefore, the scRNA-seq technique may be beneficial for researchers to identify the pathogenesis or diagnostic indicators of AM.…”

Section: Introductionmentioning

confidence: 99%

Single-cell transcriptomic analysis of eutopic endometrium and ectopic lesions of adenomyosis

Sun

Liu³

et al. 2021

Cell Biosci

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Background Adenomyosis (AM) is a common benign chronic gynaecological disorder; however, the precise pathogenesis of adenomyosis is still poorly understood. Single-cell RNA sequencing (scRNA-seq) can uncover rare subpopulations, explore genetic and functional heterogeneity, and reveal the uniqueness of each cell. It provides us a new approach to reveal biological issues from a more detailed and microscopic perspective. Here, we utilize this revolutionary technology to identify the changes of gene expression patterns between ectopic lesions and the eutopic endometrium at the single-cell level and explore a potential novel pathogenesis of AM. Methods A control endometrium (sample with leiomyoma excluding endometrial disorders, n = 1), eutopic endometrium and ectopic lesion (from a patient with adenomyosis, n = 1) samples were analysed by scRNA-seq, and additional leiomyoma (n = 3) and adenomyosis (n = 3) samples were used to confirm colocalization and vasculogenic mimicry (VM) formation. Protein colocalization was visualized by immunofluorescence, and CD34-periodic acid-Schiff (PAS) double staining was used to assess the formation of VM. Results The scRNA-seq results suggest that cancer-, cell motility- and inflammation- (CMI) associated terms, cell proliferation and angiogenesis play important roles in the progression of AM. Moreover, the colocalization of EPCAM and PECAM1 increased significantly in the ectopic endometrium group (P < 0.05), cell subpopulation with high copy number variation (CNV) levels possessing tumour-like features existed in the ectopic lesion sample, and VNN1- and EPCAM-positive cell subcluster displayed active cell motility in endometrial epithelial cells. Furthermore, during the transformation of epithelial cells to endothelial cells, we observed the significant accumulation of VM formation (positively stained with PAS but not CD34, P < 0.05) in ectopic lesions. Conclusions In the present study, our results support the theory of adenomyosis derived from the invasion and migration of the endometrium. Moreover, cell subcluster with high CNV level and tumour-associated characteristics is identified. Furthermore, epithelial-endothelial transition (EET) and the formation of VM in tumours, the latter of which facilitates the blood supply and plays an important role in maintaining cell growth, were also confirmed to occur in AM. These results indicated that the inhibition of EET and VM formation may be a potential strategy for AM management.

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“…© 2020 American Association for Cancer cancerdiscovery.aacrjournals.org Downloaded from Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on November 6, 2020; DOI: 10.1158/2159-8290.CD-20-0818tumors in comparison to KPCA in the omental tumors using RNA in situ (RNA-scope) methodology(59) (Figure 6F).…”

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confidence: 99%

Genetically Defined Syngeneic Mouse Models of Ovarian Cancer as Tools for the Discovery of Combination Immunotherapy

et al. 2021

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have patents pending. P.T.H. is a co-founder and member of the Board of Directors of LayerBio, Inc. She is on the Scientific Advisory Board of Moderna, Inc. and the Board of Directors of Alector, Inc., and she receives consulting fees and holds equity in these companies. P.T.H. is not aware of any conflicts of interest concerning the manuscript's content and topic and these entities. B.G.N. is a cofounder, holds equity in, and is a member of the Scientific Advisory Board at Navire Pharmaceuticals. He also has equity in and is a member of the Scientific Advisory Board at Avrinas, Inc. B.G.N. was an expert witness for the Johnson and Johnson ovarian cancer talc litigation in U.S. Federal Court. His spouse has equity in Amgen, Avrinas, Inc, Gilead Sciences, and Regeneron. R.A.W. is a scientific advisor for and holds an equity interest in Verastem, Inc. The other authors declare no conflicts of interest. Research.

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Single-cell sequencing of neonatal uterus reveals an Misr2+ endometrial progenitor indispensable for fertility

Cited by 43 publications

References 60 publications

Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic

Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic

Single-cell transcriptomic analysis of eutopic endometrium and ectopic lesions of adenomyosis

Genetically Defined Syngeneic Mouse Models of Ovarian Cancer as Tools for the Discovery of Combination Immunotherapy

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