scholarly journals Cell-specific Characterization of the Placental Methylome

2020 ◽  
Author(s):  
Victor Yuan ◽  
Desmond Hui ◽  
Yifan Yin ◽  
Maria Peñaherrera ◽  
Alexander Beristain ◽  
...  
Keyword(s):  
Placental Tissue ◽  
Cell Types ◽  
First Trimester ◽  
R Package ◽  
Cell Populations ◽  
Placental Development ◽  
Methylation Array ◽  
Cell Composition ◽  
Distinct Cell ◽  
Hofbauer Cells

Abstract Background: DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n=9) and term (n=19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at >850,000 CpGs.Results: The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare fetal-derived macrophage population. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation.Conclusions: Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from dbGAP (phs002013.v1.p1), through interactive exploration from the web browser (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.

scholarly journals Cell-specific characterization of the placental methylome

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Victor Yuan ◽  
Desmond Hui ◽  
Yifan Yin ◽  
Maria S. Peñaherrera ◽  
Alexander G. Beristain ◽  
...  
Keyword(s):  
Placental Tissue ◽  
Cell Types ◽  
First Trimester ◽  
R Package ◽  
Cell Populations ◽  
Placental Development ◽  
Methylation Array ◽  
Cell Composition ◽  
Distinct Cell ◽  
Hofbauer Cells

Abstract Background DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n = 9) and term (n = 19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at > 850,000 CpGs. Results The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare fetal-derived macrophage population. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation. Conclusions Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from GEO (GSE159526), through interactive exploration from the web browser (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.

scholarly journals Cell-specific Characterization of the Placental Methylome

2020 ◽  
Author(s):  
Victor Yuan ◽  
Desmond Hui ◽  
Yifan Yin ◽  
Maria Peñaherrera ◽  
Alexander Beristain ◽  
...  
Keyword(s):  
Placental Tissue ◽  
Cell Types ◽  
First Trimester ◽  
R Package ◽  
Cell Populations ◽  
Placental Development ◽  
Methylation Array ◽  
Cell Composition ◽  
Distinct Cell ◽  
Hofbauer Cells

Abstract Background: DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n=9) and term (n=19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at >850,000 CpGs.Results: The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare fetal-derived macrophage population. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation.Conclusions: Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from GEO (GSE159526), through interactive exploration from the web browser (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.

scholarly journals Cell-specific Characterization of the Placental Methylome

2020 ◽  
Author(s):  
Victor Yuan ◽  
Desmond Hui ◽  
Yifan Yin ◽  
Maria Peñaherrera ◽  
Alexander Beristain ◽  
...  
Keyword(s):  
Placental Tissue ◽  
Cell Types ◽  
First Trimester ◽  
R Package ◽  
Cell Populations ◽  
Placental Development ◽  
Methylation Array ◽  
Cell Composition ◽  
Distinct Cell ◽  
Hofbauer Cells

Abstract Background DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n = 9) and term (n = 19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at > 850,000 CpGs. Results The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare understudied macrophage population thought to derive from fetal monocytes. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation. Conclusions Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from dbGAP (phs002013.v1.p1), through interactive exploration from the web browser (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.

scholarly journals Chemogenetic Tools for Causal Cellular and Neuronal Biology

2018 ◽  
Vol 98 (1) ◽  
pp. 391-418 ◽  
Author(s):  
Deniz Atasoy ◽  
Scott M. Sternson
Keyword(s):  
G Protein ◽  
Ex Vivo ◽  
Cell Types ◽  
Cell Populations ◽  
Specific Cell ◽  
Cellular Processes ◽  
Distinct Cell ◽  
G Protein Coupled ◽  
Pharmacological Control

Chemogenetic technologies enable selective pharmacological control of specific cell populations. An increasing number of approaches have been developed that modulate different signaling pathways. Selective pharmacological control over G protein-coupled receptor signaling, ion channel conductances, protein association, protein stability, and small molecule targeting allows modulation of cellular processes in distinct cell types. Here, we review these chemogenetic technologies and instances of their applications in complex tissues in vivo and ex vivo.

scholarly journals Sexually Dimorphic Crosstalk at the Maternal-Fetal Interface

2020 ◽  
Vol 105 (12) ◽  
pp. e4831-e4847 ◽  
Author(s):  
Tianyanxin Sun ◽  
Tania L Gonzalez ◽  
Nan Deng ◽  
Rosemarie DiPentino ◽  
Ekaterina L Clark ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Types ◽  
First Trimester ◽  
Sexually Dimorphic ◽  
Receptor Ligand ◽  
Fetal Sex ◽  
Ligand Interactions ◽  
Hofbauer Cells ◽  
The Impact ◽  
Maternal Fetal Interface

Abstract Context Crosstalk through receptor ligand interactions at the maternal-fetal interface is impacted by fetal sex. This affects placentation in the first trimester and differences in outcomes. Sexually dimorphic signaling at early stages of placentation are not defined. Objective Investigate the impact of fetal sex on maternal-fetal crosstalk. Design Receptors/ligands at the maternal-fetal surface were identified from sexually dimorphic genes between fetal sexes in the first trimester placenta and defined in each cell type using single-cell RNA-Sequencing (scRNA-Seq). Setting Academic institution. Samples Late first trimester (~10-13 weeks) placenta (fetal) and decidua (maternal) from uncomplicated ongoing pregnancies. Main outcome measures Transcriptomic profiling at tissue and single-cell level; immunohistochemistry of select proteins. Results We identified 91 sexually dimorphic receptor-ligand pairs across the maternal-fetal interface. We examined fetal sex differences in 5 major cell types (trophoblasts, stromal cells, Hofbauer cells, antigen-presenting cells, and endothelial cells). Ligands from the CC family chemokine ligand (CCL) family were most highly representative in females, with their receptors present on the maternal surface. Sexually dimorphic trophoblast transcripts, Mucin-15 (MUC15) and notum, palmitoleoyl-protein carboxylesterase (NOTUM) were also most highly expressed in syncytiotrophoblasts and extra-villous trophoblasts respectively. Gene Ontology (GO) analysis using sexually dimorphic genes in individual cell types identified cytokine mediated signaling pathways to be most representative in female trophoblasts. Upstream analysis demonstrated TGFB1 and estradiol to affect all cell types, but dihydrotestosterone, produced by the male fetus, was an upstream regulator most significant for the trophoblast population. Conclusions Maternal-fetal crosstalk exhibits sexual dimorphism during placentation early in gestation.

scholarly journals Single-cell Transcriptomics Identify Extensive Heterogeneity in the Cellular Composition of Mouse Achilles Tendons

2019 ◽  
Author(s):  
Andrea J De Micheli ◽  
Jacob B Swanson ◽  
Nathaniel P Disser ◽  
Leandro M Martinez ◽  
Nicholas R Walker ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Types ◽  
Tissue Homeostasis ◽  
Cellular Heterogeneity ◽  
Cell Populations ◽  
Cellular Composition ◽  
Matrix Assembly ◽  
Distinct Cell ◽  
Single Cell Rna Sequencing ◽  
Additional Support

AbstractTendon is a connective tissue that transmits forces between muscles and bones. Cellular heterogeneity is increasingly recognized as an important factor in the biological basis of tissue homeostasis and disease, but little is known about the diversity of cells that populate tendon. Our objective was to explore the heterogeneity of cells in mouse Achilles tendons using single-cell RNA sequencing. We assembled a transcriptomic atlas and identified 11 distinct cell types in tendons, including 3 previously undescribed populations of fibroblasts. Using trajectory inference analysis, we provide additional support for the notion that pericytes are progenitor cells for the fibroblasts that compose adult tendons. We also modeled cell-interactions and identified ligand-receptor pairs involved in tendon homeostasis. Our findings highlight notable heterogeneity between and within tendon cell populations, which may contribute to our understanding of tendon extracellular matrix assembly and maintenance, and inform the design of therapies to treat tendinopathies.

scholarly journals spicyR: Spatial analysis of in situ cytometry data in R

2021 ◽  
Author(s):  
Nicolas Paolo Canete ◽  
Sourish Suresh Iyengar ◽  
John T Ormerod ◽  
Andrew N Harman ◽  
Ellis Patrick
Keyword(s):  
Spatial Analysis ◽  
Disease Process ◽  
Simulated Data ◽  
High Sensitivity ◽  
Cell Types ◽  
R Package ◽  
Comprehensive Overview ◽  
Histological Techniques ◽  
Disease States ◽  
Distinct Cell

Motivation: High parameter histological techniques have allowed for the identification of a variety of distinct cell types within an image, providing a comprehensive overview of the tissue environment. This allows the complex cellular architecture and environment of diseased tissue to be explored. While spatial analysis techniques have revealed how cell-cell interactions are important within the disease pathology, there remains a gap in exploring changes in these interactions within the disease process. Specifically, there are currently no established methods for performing inference on cell localisation changes across images, hindering an understanding of how cellular environments change with a disease pathology. Results: We have developed the spicyR R package to perform inference on changes in the spatial localisation of cell types across groups of images. Application to simulated data demonstrates a high sensitivity and specificity. We demonstrate the utility of spicyR by applying it to a type 1 diabetes imaging mass cytometry dataset, revealing changes in cellular associations that were relevant to the disease progression. Ultimately, spicyR allows changes in cellular environments to be explored under different pathologies or disease states.

Immunocytochemical identification of cytotrophoblast from other mononuclear cell populations isolated from first-trimester human chorionic villi

1985 ◽  
Vol 76 (1) ◽  
pp. 189-197
Author(s):  
B.H. Butterworth ◽  
Y.W. Loke
Keyword(s):  
Monoclonal Antibodies ◽  
Mononuclear Cell ◽  
Chorionic Villus ◽  
Cell Types ◽  
First Trimester ◽  
Cell Populations ◽  
Double Labelling ◽  
Chorionic Villi ◽  
Isolation Methods ◽  
Human Placental Cells

Trophoblast biologists are often uncertain as to what cell types they are investigating because the mononuclear cell populations prepared from trypsinization of human first-trimester chorionic villi are morphologically very similar. In the present study, immunocytochemical and phagocytic markers have been used to distinguish cytotrophoblast populations from cell types derived from the mesenchyme of the chorionic villus. Two anti-trophoblast monoclonal antibodies generated in our own laboratory (18B/A5 and 18A/C4) were found to be very efficient in identifying cytotrophoblast, which made up 35–40% of the cells in a smear. Most cytotrophoblast cells did not stain with a monoclonal anti-HLA-A,B,C antibody but a few cells (5%) were found to express both trophoblast and HLA-A,B,C antigens by a double-labelling technique. Endothelial cells from villous capillaries could be identified by a rabbit anti-factor VIII antibody. These cells formed 28% of the population in a cytospin smear. Macrophages from the villous mesenchyme were less readily separable as neither specific monoclonal antibodies nor localization of enzymes were found to be effective. However, these cells could be identified by their ability to phagocytose carmine. About 15% of the cells in a smear consisted of macrophages. The procedure described should prove useful in judging the efficiency of isolation methods from human placental cells.

scholarly journals Insulin-like growth factor I and II regulate the life cycle of trophoblast in the developing human placenta

2008 ◽  
Vol 294 (6) ◽  
pp. C1313-C1322 ◽  
Author(s):  
Karen Forbes ◽  
Melissa Westwood ◽  
Philip N. Baker ◽  
John D. Aplin
Keyword(s):  
Mapk Pathway ◽  
Indirect Evidence ◽  
First Trimester ◽  
Cell Populations ◽  
Placental Development ◽  
Igf I ◽  
Signaling Inhibitors ◽  
Phosphoinositide 3 Kinase ◽  
Kinase Pathway ◽  
Insulin Like Growth Factors

The main disorders of human pregnancy are rooted in defective placentation. Normal placental development depends on proliferation, differentiation, and fusion of cytotrophoblasts to form and maintain an overlying syncytiotrophoblast. There is indirect evidence that the insulin-like growth factors (IGFs), which are aberrant in pregnancy disorders, are involved in regulating trophoblast turnover, but the processes that control human placental growth are poorly understood. Using an explant model of human first-trimester placental villus in which the spatial and ontological relationships between cell populations are maintained, we demonstrate that cytotrophoblast proliferation is enhanced by IGF-I/IGF-II and that both factors can rescue cytotrophoblast from apoptosis. Baseline cytotrophoblast proliferation ceases in the absence of syncytiotrophoblast, although denuded cytotrophoblasts can proliferate when exposed to IGF and the rate of cytotrophoblast differentiation/fusion and, consequently, syncytial regeneration, increases. Use of signaling inhibitors suggests that IGFs mediate their effect on cytotrophoblast proliferation/syncytial formation through the MAPK pathway, whereas effects on survival are regulated by the phosphoinositide 3-kinase pathway. These results show that directional contact between cytotrophoblast and syncytium is important in regulating the relative amounts of the two cell populations. However, IGFs can exert an exogenous regulatory influence on placental growth/development, suggesting that manipulation of the placental IGF axis may offer a potential therapeutic route to the correction of inadequate placental growth.

scholarly journals Zika Virus Infection at Different Pregnancy Stages: Anatomopathological Findings, Target Cells and Viral Persistence in Placental Tissues

2018 ◽  
Author(s):  
Lucia de Noronha ◽  
Camila Zanluca ◽  
Marion Burger ◽  
Andreia Akemi Suzukawa ◽  
Marina Azevedo ◽  
...  
Keyword(s):  
Zika Virus ◽  
Congenital Malformations ◽  
Acute Infection ◽  
Histological Finding ◽  
Placental Tissue ◽  
Cell Types ◽  
Target Cells ◽  
Third Trimester ◽  
Zikv Infection ◽  
Hofbauer Cells

ABSTRACTZika virus (ZIKV) infection in humans has been associated with congenital malformations and other neurological disorders, such as Guillain-Barré syndrome. The mechanism(s) of ZIKV intrauterine transmission, the cell types involved, the most vulnerable period of pregnancy for severe outcomes from infection and other physiopathological aspects remain unknown. In this study, we analyzed placental samples obtained at the time of delivery from a group of twenty-four women diagnosed with ZIKV infection during the first, second or third trimesters of pregnancy. Villous immaturity was the main histological finding in the placental tissues, although placentas without alterations were also frequently observed. Significant enhancement of the number of syncytial sprouts was observed in the placentas of women infected during the third trimester, indicating the development of placental abnormalities after ZIKV infection. Hyperplasia of Hofbauer cells (HCs) was also observed in these third-trimester placental tissues, and remarkably, HCs were the only ZIKV-positive fetal cells found in the placentas studied that persisted until birth, as revealed by immunohistochemical (IHC) analysis. Thirty-three percent of women infected during pregnancy delivered infants with congenital abnormalities, although no pattern correlating the gestational stage at infection, the IHC positivity of HCs in placental tissues and the presence of congenital malformations at birth was observed. Placental tissue analysis enabled us to confirm maternal ZIKV infection in cases where serum from the acute infection phase was not available, which reinforces the importance of this technique in identifying possible causal factors of birth defects. The results we observed in the samples from naturally infected pregnant women may contribute to the understanding of some aspects of the pathophysiology of ZIKV.

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