Transcription factor networks in trophoblast development

Papúchová, Henrieta; Latos, Paulina A.

doi:10.1007/s00018-022-04363-6

Cited by 46 publications

(39 citation statements)

References 131 publications

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“…Pathways of nutrient transport and mammary gland development were also identified (Figure 4D). In EVT, pathways such as the epithelial to mesenchyme transition pathway, epithelial development and differentiation, extracellular matrix organization were identified as previously described (Illsley et al, 2020;Papuchova and Latos, 2022), which were associated with the invasive activities of EVT (Figure 4D; Supplementary Table S5).…”

Section: Spatial Regulatory Activity Of Transcription Factors In Villimentioning

confidence: 64%

Resolving the gene expression maps of human first-trimester chorionic villi with spatial transcriptome

Liu

Zhai

Zhang

et al. 2022

Front. Cell Dev. Biol.

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The placenta is important for fetal development in mammals, and spatial transcriptomic profiling of placenta helps to resolve its structure and function. In this study, we described the landscape of spatial transcriptome of human placental villi obtained from two pregnant women at the first trimester using the modified Stereo-seq method applied for paraformaldehyde (PFA) fixation samples. The PFA fixation of human placenta villi was better than fresh villi embedded in optimum cutting temperature (OCT) compound, since it greatly improved tissue morphology and the specificity of RNA signals. The main cell types in chorionic villi such as syncytiotrophoblasts (SCT), villous cytotrophoblasts (VCT), fibroblasts (FB), and extravillous trophoblasts (EVT) were identified with the spatial transcriptome data, whereas the minor cell types of Hofbauer cells (HB) and endothelial cells (Endo) were spatially located by deconvolution of scRNA-seq data. We demonstrated that the Stereo-seq data of human villi could be used for sophisticated analyses such as spatial cell-communication and regulatory activity. We found that the SCT and VCT exhibited the most ligand-receptor pairs that could increase differentiation of the SCT, and that the spatial localization of specific regulons in different cell types was associated with the pathways related to hormones transport and secretion, regulation of mitotic cell cycle, and nutrient transport pathway in SCT. In EVT, regulatory pathways such as the epithelial to mesenchyme transition, epithelial development and differentiation, and extracellular matrix organization were identified. Finally, viral receptors and drug transporters were identified in villi according to the pathway analysis, which could help to explain the vertical transmission of several infectious diseases and drug metabolism efficacy. Our study provides a valuable resource for further investigation of the placenta development, physiology and pathology in a spatial context.

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Section: Spatial Regulatory Activity Of Transcription Factors In Villimentioning

confidence: 64%

Resolving the gene expression maps of human first-trimester chorionic villi with spatial transcriptome

Liu

Zhai

Zhang

et al. 2022

Front. Cell Dev. Biol.

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“…( 49 ) reported that knockdown of ribosomal protein L39 ( RPL39 ) inhibited the proliferation, migration, and invasion of trophoblast cells in vitro . APO was closely related to abnormal biological function of trophoblasts, since trophoblast cells were vital to placental and fetus development ( 50 , 51 ). Therefore, the expression of SEZ6 and LPAR4 might play potential pathogenic role in APO.…”

Section: Discussionmentioning

confidence: 99%

Potential genetic biomarkers predict adverse pregnancy outcome during early and mid-pregnancy in women with systemic lupus erythematosus

et al. 2022

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BackgroundEffectively predicting the risk of adverse pregnancy outcome (APO) in women with systemic lupus erythematosus (SLE) during early and mid-pregnancy is a challenge. This study was aimed to identify potential markers for early prediction of APO risk in women with SLE.MethodsThe GSE108497 gene expression dataset containing 120 samples (36 patients, 84 controls) was downloaded from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was performed, and differentially expressed genes (DEGs) were screened to define candidate APO marker genes. Next, three individual machine learning methods, random forest, support vector machine-recursive feature elimination, and least absolute shrinkage and selection operator, were combined to identify feature genes from the APO candidate set. The predictive performance of feature genes for APO risk was assessed using area under the receiver operating characteristic curve (AUC) and calibration curves. The potential functions of these feature genes were finally analyzed by conventional gene set enrichment analysis and CIBERSORT algorithm analysis.ResultsWe identified 321 significantly up-regulated genes and 307 down-regulated genes between patients and controls, along with 181 potential functionally associated genes in the WGCNA analysis. By integrating these results, we revealed 70 APO candidate genes. Three feature genes, SEZ6, NRAD1, and LPAR4, were identified by machine learning methods. Of these, SEZ6 (AUC = 0.753) showed the highest in-sample predictive performance for APO risk in pregnant women with SLE, followed by NRAD1 (AUC = 0.694) and LPAR4 (AUC = 0.654). After performing leave-one-out cross validation, corresponding AUCs for SEZ6, NRAD1, and LPAR4 were 0.731, 0.668, and 0.626, respectively. Moreover, CIBERSORT analysis showed a positive correlation between regulatory T cell levels and SEZ6 expression (P < 0.01), along with a negative correlation between M2 macrophages levels and LPAR4 expression (P < 0.01).ConclusionsOur preliminary findings suggested that SEZ6, NRAD1, and LPAR4 might represent the useful genetic biomarkers for predicting APO risk during early and mid-pregnancy in women with SLE, and enhanced our understanding of the origins of pregnancy complications in pregnant women with SLE. However, further validation was required.

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“…The copyright holder for this preprint this version posted August 3, 2022. ; https://doi.org/10.1101/2022.08.02.502490 doi: bioRxiv preprint lineage-specific expression (Papuchova and Latos 2022). Starting with in-depth inspection of the primate-specific MER41 family followed by comprehensive analysis on candidate TFs and the entire ERVome, this study aims to better understand the regulation and function of ERV-associated enhancers in the human trophoblast regulatory network.…”

Section: Discussionmentioning

confidence: 99%

“…We recently demonstrated that dozens of ERV families – many are primate-specific – create numerous human placental enhancers (Sun et al 2021), yet the underlying regulatory mechanism remains to be explored. Furthermore, it is also highly desirable to delineate how ERV-associated enhancers participate in the trophoblast gene network, which is under the cooperative regulation of many TFs – including some with lineage-specific expression (Papuchova and Latos 2022). Starting with in-depth inspection of the primate-specific MER41 family followed by comprehensive analysis on candidate TFs and the entire ERVome, this study aims to better understand the regulation and function of ERV-associated enhancers in the human trophoblast regulatory network.…”

Section: Discussionmentioning

confidence: 99%

Prevalent regulation of GATA2/3 and MSX2 on endogenous retrovirus-derived regulatory elements in human trophoblast stem cells

Jiang

et al. 2022

Preprint

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The placenta is an organ with extraordinary phenotypic diversity in eutherian mammals. Recent evidence suggests that numerous human placental enhancers are evolved from lineage-specific insertions of endogenous retroviruses (ERVs), yet the transcription factors (TFs) underlying their regulation remain largely elusive. Here, by first focusing on MER41, a primate-specific ERV family previously linked to placenta and innate immunity, we uncover the binding motifs of multiple crucial trophoblast TFs (GATA2/3, MSX2, GRHL2) in addition to innate immunity TFs STAT1 and IRF1. Integration of ChIP-Seq data confirms the binding of GATA2/3 and MSX2 on the majority of MER41-derived enhancers in human trophoblast stem cells (TSCs). Notably, MER41-derived enhancers that are constitutively active in human TSCs are distinct from those activated upon interferon stimulation, which is determined by the binding of trophoblast TFs and their sub-family compositions. We further demonstrate that GATA2/3 and MSX2 have prevalent binding on numerous other ERV families – indicating their broad impact on ERV-derived placental enhancers. Functionally, the derepression of many syncytiotrophoblast genes after disruption of MSX2 is likely to be mediated by regulatory elements derived from ERVs – suggesting ERVs are also important for mediating transcriptional repression. Overall, this study characterized the prevalent binding of GATA2/3, MSX2 and their co-factors on ERV-derived regulatory elements in human TSCs and provided mechanistic insights into the importance of ERVs in human trophoblast regulatory network.

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Transcription factor networks in trophoblast development

Cited by 46 publications

References 131 publications

Resolving the gene expression maps of human first-trimester chorionic villi with spatial transcriptome

Resolving the gene expression maps of human first-trimester chorionic villi with spatial transcriptome

Potential genetic biomarkers predict adverse pregnancy outcome during early and mid-pregnancy in women with systemic lupus erythematosus

Prevalent regulation of GATA2/3 and MSX2 on endogenous retrovirus-derived regulatory elements in human trophoblast stem cells

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