scholarly journals Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window

2018 ◽  
Author(s):  
Emma S Lucas ◽  
Pavle Vrljicak ◽  
Joanne Muter ◽  
Maria M Diniz-da-Costa ◽  
Paul J Brighton ◽  
...  
Keyword(s):  
Single Cell ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Single Cell Analysis ◽  
Immune Surveillance ◽  
Marker Genes ◽  
Implantation Window ◽  
Decidual Cells

AbstractBreakdown of the feto-maternal interface in early pregnancy causes miscarriage. The cycling endometrium becomes poised to transition to a pregnant state during the midluteal implantation window, coinciding with differentiation of stromal cells into decidual cells (DC) and emergence of senescent decidual cells (snDC). Emerging evidence suggests that DC engage uterine natural killer cells to eliminate their senescent counterparts, thus enabling formation of a robust decidual matrix in pregnancy. To examine if failure to constrain snDC during the peri-implantation window increases the risk of miscarriage, we reconstructed the decidual pathway at single-cell levelin vitroand demonstrated that, without immune surveillance, secondary senescence rapidly transforms DC into progesterone-resistant cells that abundantly express extracellular matrix remodelling factors. Additional single-cell analysis of midluteal endometrium identifiedDIO2andSCARA5as marker genes of a diverging decidual responsein vivo. Finally, we report a conspicuous link between a pro-senescent decidual response in luteal phase endometrium and recurrent pregnancy loss, suggesting that pre-pregnancy screening and intervention may reduce the burden of miscarriage.

scholarly journals Single Cell Analysis Reveals That IL-4 Receptor/Stat6 Signaling Is Not Required for the In Vivo or In Vitro Development of CD4+Lymphocytes with a Th2 Cytokine Profile

2000 ◽  
Vol 164 (6) ◽  
pp. 3047-3055 ◽  
Author(s):  
Dragana Jankovic ◽  
Marika C. Kullberg ◽  
Nancy Noben-Trauth ◽  
Patricia Caspar ◽  
William E. Paul ◽  
...  
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Cytokine Profile ◽  
Cell Analysis ◽  
In Vitro Development ◽  
Th2 Cytokine ◽  
Vitro Development ◽  
Cd4 Lymphocytes

scholarly journals LEFTY, a Member of the Transforming Growth Factor-β Superfamily, Inhibits Uterine Stromal Cell Differentiation: A Novel Autocrine Role

Endocrinology ◽  
2010 ◽  
Vol 151 (3) ◽  
pp. 1320-1330 ◽  
Author(s):  
Meiyi Tang ◽  
Devendra Naidu ◽  
Patrick Hearing ◽  
Stuart Handwerger ◽  
Siamak Tabibzadeh
Keyword(s):  
Medroxyprogesterone Acetate ◽  
Transforming Growth Factor ◽  
Marker Genes ◽  
Specific Marker ◽  
Normal Endometrium ◽  
Ovariectomized Mice ◽  
Decidual Cells ◽  
Pregnant Mice

LEFTY is expressed in normal endometrium in cells that decidualize. To understand the importance of this expression, we have studied the effect of LEFTY on decidualization in vitro and in vivo. Exposure of human uterine fibroblast (HuF) cells to recombinant LEFTY blocked the induction of the decidual differentiation-specific marker genes, IGFBP1 (IGF-binding protein 1) and PRL (prolactin) in response to medroxyprogesterone acetate, estradiol, and prostaglandin E2. The inhibitory effect was associated with decreased induction of the transcription factors ETS1 and FOXO1, both of which are essential for decidualization. Overexpression of LEFTY in decidualized HuF cells with an adenovirus that transduced LEFTY caused a marked decrease in IGFBP1 secretion, and withdrawal of medroxyprogesterone acetate from decidualized cells resulted in a decrease in IGFBP1 secretion and an increase in LEFTY expression. Moreover, overexpression of LEFTY in decidualized cells reprogrammed the cells to a less differentiated state and attenuated expression of decidual markers. Uterine decidualization was markedly attenuated and litter size was significantly reduced by retroviral transduction of LEFTY in the uterine horns of pregnant mice or by induction of LEFTY expression by doxycycline treatment in Tet-On conditional LEFTY transgenic pregnant mice. In addition, administration of the contraceptive agent drospirenone to ovariectomized mice induced a marked increase in LEFTY expression and inhibited decidualization. Taken together, these finding indicate that LEFTY acts as a molecular switch that modulates both the induction of decidual differentiation and the maintenance of a decidualized state. Because decidual cells express abundant amounts of LEFTY, the action of LEFTY on decidualization occurs by an autocrine mechanism.

Single-cell analysis of prostaglandin E2-induced human decidual cell in vitro differentiation: A minimal ancestral deciduogenic signal

2021 ◽  
Author(s):  
Daniel J Stadtmauer ◽  
Günter P Wagner
Keyword(s):  
Cyclic Amp ◽  
Prostaglandin E2 ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Core Gene ◽  
Decidual Cell ◽  
A Genome ◽  
Decidual Cells ◽  
Activated State

Abstract The decidua is a hallmark of reproduction in many placental mammals. Differentiation of decidual stromal cells is known to be induced by progesterone and the cyclic AMP/protein kinase A (cAMP/PKA) pathway. Several candidates have been identified as the physiological stimulus for adenylyl cyclase activation, but their relative importance remains unclear. To bypass this uncertainty, the standard approach for in vitro experiments uses membrane-permeable cyclic AMP and progestin. We phylogenetically infer that prostaglandin E2 (PGE2) likely was the signal that ancestrally induced decidualization in conjunction with progesterone. This suggests that PGE2 and progestin should be able to activate the core gene regulatory network of decidual cells. To test this prediction we performed a genome-wide study of gene expression in human endometrial fibroblasts decidualized with PGE2 and progestin. Comparison to a cAMP-based protocol revealed shared activation of core decidual genes, and decreased induction of senescence-associated genes. Single-cell transcriptomics of PGE2-mediated decidualization revealed a distinct early activated state transitioning to a differentiated decidual state. PGE2-mediated decidualization was found to depend upon progestin-dependent induction of PGE2 receptor 2 (PTGER2) which in turn leads to PKA activation upon PGE2 stimulation. Progesterone-dependent induction of PTGER2 is absent in opossum, an outgroup taxon of placental mammals which is incapable of decidualization. Together, these findings suggest that the origin of decidualization involved the evolution of progesterone-dependent activation of the PGE2/PTGER2/PKA axis, facilitating entry into a PKA-dominant rather than AKT-dominant cellular state. We propose the use of PGE2 for in vitro decidualization as an alternative to 8-Br-cAMP.

scholarly journals Single Cell RNA Sequencing Identifies Subsets of Hepatic Stellate Cells and Myofibroblasts in Liver Fibrosis

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 503 ◽  
Author(s):  
Oliver Krenkel ◽  
Jana Hundertmark ◽  
Thomas Ritz ◽  
Ralf Weiskirchen ◽  
Frank Tacke
Keyword(s):  
Liver Fibrosis ◽  
Single Cell ◽  
Rna Sequencing ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Marker Genes ◽  
Gene And Protein Expression ◽  
Single Cell Rna Sequencing

Activation of hepatic stellate cells (HSCs) and their trans-differentiation towards collagen-secreting myofibroblasts (MFB) promote liver fibrosis progression. During chronic liver disease, resting HSCs become activated by inflammatory and injury signals. However, HSCs/MFB not only produce collagen, but also secrete cytokines, participate in metabolism, and have biomechanical properties. We herein aimed to characterize the heterogeneity of these liver mesenchymal cells by single cell RNA sequencing. In vivo resting HSCs or activated MFB were isolated from C57BL6/J mice challenged by carbon tetrachloride (CCl4) intraperitoneally for 3 weeks to induce liver fibrosis and compared to in vitro cultivated MFB. While resting HSCs formed a homogenous population characterized by high platelet derived growth factor receptor β (PDGFRβ) expression, in vivo and in vitro activated MFB split into heterogeneous populations, characterized by α-smooth muscle actin (α-SMA), collagens, or immunological markers. S100 calcium binding protein A6 (S100A6) was a universal marker of activated MFB on both the gene and protein expression level. Compared to the heterogeneity of in vivo MFB, MFB in vitro sequentially and only transiently expressed marker genes, such as chemokines, during culture activation. Taken together, our data demonstrate the heterogeneity of HSCs and MFB, indicating the existence of functionally relevant subsets in hepatic fibrosis.

scholarly journals Single-cell analysis of RORα tracer mouse lung reveals ILC progenitors and effector ILC2 subsets

2019 ◽  
Vol 217 (3) ◽  
Author(s):  
Maryam Ghaedi ◽  
Zi Yi Shen ◽  
Mona Orangi ◽  
Itziar Martinez-Gonzalez ◽  
Lisa Wei ◽  
...  
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Retinoic Acid Receptor ◽  
Allergic Inflammation ◽  
Lymphoid Cells ◽  
Orphan Receptor ◽  
Mouse Lung ◽  
Mouse Lungs

Lung group 2 innate lymphoid cells (ILC2s) drive allergic inflammation and promote tissue repair. ILC2 development is dependent on the transcription factor retinoic acid receptor–related orphan receptor (RORα), which is also expressed in common ILC progenitors. To elucidate the developmental pathways of lung ILC2s, we generated RORα lineage tracer mice and performed single-cell RNA sequencing, flow cytometry, and functional analyses. In adult mouse lungs, we found an IL-18Rα+ST2− population different from conventional IL-18Rα−ST2+ ILC2s. The former was GATA-3intTcf7EGFP+Kit+, produced few cytokines, and differentiated into multiple ILC lineages in vivo and in vitro. In neonatal mouse lungs, three ILC populations were identified, namely an ILC progenitor population similar to that in adult lungs and two distinct effector ILC2 subsets that differentially produced type 2 cytokines and amphiregulin. Lung ILC progenitors might actively contribute to ILC-poiesis in neonatal and inflamed adult lungs. In addition, neonatal lung ILC2s include distinct proinflammatory and tissue-repairing subsets.

scholarly journals Single-cell analysis reveals a nestin+ tendon stem/progenitor cell population with strong tenogenic potentiality

2016 ◽  
Vol 2 (11) ◽  
pp. e1600874 ◽  
Author(s):  
Zi Yin ◽  
Jia-jie Hu ◽  
Long Yang ◽  
Ze-Feng Zheng ◽  
Cheng-rui An ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Cell Population ◽  
Single Cell Analysis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Analysis ◽  
Nestin Expression

The repair of injured tendons remains a formidable clinical challenge because of our limited understanding of tendon stem cells and the regulation of tenogenesis. With single-cell analysis to characterize the gene expression profiles of individual cells isolated from tendon tissue, a subpopulation of nestin+ tendon stem/progenitor cells (TSPCs) was identified within the tendon cell population. Using Gene Expression Omnibus datasets and immunofluorescence assays, we found that nestin expression was activated at specific stages of tendon development. Moreover, isolated nestin+ TSPCs exhibited superior tenogenic capacity compared to nestin− TSPCs. Knockdown of nestin expression in TSPCs suppressed their clonogenic capacity and reduced their tenogenic potential significantly both in vitro and in vivo. Hence, these findings provide new insights into the identification of subpopulations of TSPCs and illustrate the crucial roles of nestin in TSPC fate decisions and phenotype maintenance, which may assist in future therapeutic strategies to treat tendon disease.

scholarly journals The Trends of Single-Cell Analysis: A Global Study

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Hua Tian ◽  
Haifeng Liu ◽  
Yuanyuan Zhu ◽  
Dan Xing ◽  
Bin Wang
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Bibliographic Coupling ◽  
In Vivo Studies ◽  
Cell Analysis ◽  
The Usa ◽  
Visualization Of Data ◽  
Number Of Publications

Objective. The field of single-cell analysis has rapidly grown worldwide, and a bibliometric analysis and visualization of data and publications pertaining to such single-cell research has the potential to offer insights into the development of this field over the past two decades while also highlighting future avenues of research. Methods. Single-cell analysis-related studies published from 2000-2019 were identified through searches of the Web of Science, Scopus, and PubMed databases, and corresponding bibliometric data were systematically compiled. Extracted data from each study included author names, country of origin, and affiliations. GraphPad Prism was used to analyze these data, while VOSviewer was used to perform global analyses of bibliographic coupling, coauthorship, cocitation, and co-occurrence. Results. In total, 4,071 relevant studies were included in this analysis. The number of publications increased substantially with time, suggesting that single-cell analyses are becoming increasingly more prevalent in recent years. Studies from the USA had the greatest impact in this field, with higher H -index values and numbers of citations relative to other countries, whereas Israel exhibited the highest average number of citations per publication. Bibliographic coupling, coauthorship, cocitation, and co-occurrence analyses revealed that Analytical Chemistry was associated with the highest number of publications in this field, and the University of Stanford contributed the most to this field. The most cited study included in this analysis was published by Macosko et al. in 2015 in Cell. Co-occurrence analyses revealed that the most common single-cell research topics included “mechanistic studies,” “in vitro studies,” “in vivo studies,” and “fabrication studies.” Conclusions. Single-cell analyses are a rapidly growing area of scientific interest, and higher volumes of publications in this field are expected in the coming years, particularly for studies conducting fabrication and in vivo single-cell analyses.

scholarly journals Assessing the Heterogeneity of Cardiac Non-myocytes and the Effect of Cell Culture with Integrative Single Cell Analysis

2020 ◽  
Author(s):  
Brian S. Iskra ◽  
Logan Davis ◽  
Henry E. Miller ◽  
Yu-Chiao Chiu ◽  
Alexander R. Bishop ◽  
...  
Keyword(s):  
Cell Culture ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Cell Types ◽  
Cell Analysis ◽  
Mass Cytometry ◽  
Single Cell Rna Sequencing ◽  
High Depth

AbstractCardiac non-myocytes comprise a diverse and crucial cell population in the heart that plays dynamic roles in cardiac wound healing and growth. Non-myocytes broadly fall into four cell types: endothelium, fibroblasts, leukocytes, and pericytes. Here we characterize the diversity of the non-myocytes in vivo and in vitro using mass cytometry. By leveraging single-cell RNA sequencing we inform the design of a mass cytometry panel. To aid in annotation of the mass cytometry datasets, we utilize data integration with a neural network. We introduce approximately 460,000∼ single cell proteomes of non-myocytes as well as 5,000∼ CD31 negative single cell transcriptomes. Using our data, as well as previously reported datasets, we characterize cardiac non-myocytes with high depth in six mice, characterizing novel surface markers (CD9, CD200, Notch3, and FolR2). Further, we find that extended cell culture promotes the proliferation of CD45+CD11b+FolR2+IAIE- myeloid cells in addition to fibroblasts.

scholarly journals Single-cell analysis of RORα tracer mouse lung reveals ILC progenitors and effector ILC2 subsets

2019 ◽  
Author(s):  
Maryam Ghaedi ◽  
Mona Orangi ◽  
Itziar Martinez-Gonzalez ◽  
Lisa Wei ◽  
Xiaoxiao Lu ◽  
...  
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Retinoic Acid Receptor ◽  
Allergic Inflammation ◽  
Lymphoid Cells ◽  
Orphan Receptor ◽  
Mouse Lung ◽  
Mouse Lungs

Lung group 2 innate lymphoid cells (ILC2s) drive allergic inflammation and promote tissue repair. ILC2 development is dependent on the transcription factor retinoic acid receptor–related orphan receptor (RORα), which is also expressed in common ILC progenitors. To elucidate the developmental pathways of lung ILC2s, we generated RORα lineage tracer mice and performed single-cell RNA sequencing, flow cytometry, and functional analyses. In adult mouse lungs, we found an IL-18Rα+ST2− population different from conventional IL-18Rα−ST2+ ILC2s. The former was GATA-3intTcf7EGFP+Kit+, produced few cytokines, and differentiated into multiple ILC lineages in vivo and in vitro. In neonatal mouse lungs, three ILC populations were identified, namely an ILC progenitor population similar to that in adult lungs and two distinct effector ILC2 subsets that differentially produced type 2 cytokines and amphiregulin. Lung ILC progenitors might actively contribute to ILC-poiesis in neonatal and inflamed adult lungs. In addition, neonatal lung ILC2s include distinct proinflammatory and tissue-repairing subsets.

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