Establishment of Human Trophoblast Stem Cells from Term Smooth Chorion
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE292125 | GEO | 2025/07/31
REPOSITORIES: GEO
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Project description:Purpose: To understand the regulatiory mechanisms of trophoblast stemness and differentiation gene expression. Methods: Three trophoblast stem cell lines were derived from individual term placnta, TSTerm #1 and TSTerm #2 TSTerm #3. The three TSTerm cell lines were differentiated into syncytiotrophoblasts (STB：ST-TSTerm #1, ST-TSTerm #2, and ST-TSTerm #3) and extravillous trophoblasts (EVT：EVT-TSTerm #1, EVT-TSTerm #2 and EVT-TSTerm #3). TS#1GCM1-KO cell line was derived from TSTerm #1 cells by depletion of GCM1 gene. ST-TS#1GCM1-KO cells were differentiated from TS#1GCM1-KO cells. Additionally, CTBTerm #1, CTBTerm #2, and CTBTerm #3 were isolated from individual placentae. The mRNA profiles of tatal fourteen samples as mentioned above were generated by sequencing, using NovaSeq Sequencing System. The raw data were analyzed by CLC Genomics Workbench v10. Conclusion: We elucidated reciprocal regulation of trophoblast stemness and differentiation gene expression, which facilitated the derivation of TS cells from term placentas.
2021-12-21 | GSE158901 | GEO
Project description:Invasive trophoblast cells are critical to spiral artery remodeling in hemochorial placentation. Insufficient trophoblast invasion and vascular remodeling can lead to pregnancy disorders including preeclampsia, preterm birth, and intrauterine growth restriction. Previous studies in the mouse identified achaete-scute homolog 2 (ASCL2) as essential to extraembryonic development. We hypothesized that ASCL2 is a critical and conserved regulator of invasive trophoblast lineage development. In contrast to the mouse, the rat possesses deep intrauterine trophoblast cell invasion and spiral artery remodeling similar to human placentation. In this report, we investigated invasive/extravillous trophoblast (EVT) cell differentiation using human trophoblast stem (TS) cells and a loss-of-function mutant Ascl2 rat model. ASCL2 transcripts are expressed in the EVT column and junctional zone, which represent tissue sources of invasive trophoblast progenitor cells within human and rat placentation sites, respectively. Differentiation of human TS cells into EVT cells resulted in significant upregulation of ASCL2 and several other transcripts indicative of EVT cell differentiation. Disruption of ASCL2 impaired EVT cell differentiation as indicated by cell morphology and transcript profiles. RNA sequencing analysis of ASCL2-deficient trophoblast cells identified both downregulation of EVT cell-associated transcripts and upregulation of syncytiotrophoblast-associated transcripts, indicative of dual activating and repressing functions. ASCL2 deficiency in the rat impacted placental morphogenesis resulting in junctional zone dysgenesis and failed intrauterine trophoblast cell invasion. ASCL2 acts as a critical and conserved regulator of invasive trophoblast cell lineage development and a species-specific modulator of the syncytiotrophoblast lineage.
2021-03-01 | GSE154350 | GEO
Project description:WNT activated signal transduction is a conserved regulator of morphogenesis of many organ systems, including the placenta. In human trophoblast stem (TS) cells, activation of canonical WNT signaling is a key to maintenance of the TS cell stem state. NOTUM, a negative regulator of canonical WNT signaling, was prominently expressed in first trimester EVT cells developing in situ and upregulated in EVT cells derived from human TS cells. Furthermore, NOTUM was required for human TS cell differentiation to EVT cells. Canonical WNT signaling is essential for maintaining human trophoblast cell stemness and prevention of human TS cell differentiation. Downregulation of canonical WNT signaling via the actions of NOTUM is required for EVT cell differentiation.
2024-03-06 | GSE206034 | GEO
Project description:WNT activated signal transduction is a conserved regulator of morphogenesis of many organ systems, including the placenta. In human trophoblast stem (TS) cells, activation of canonical WNT signaling is a key to maintenance of the TS cell stem state. NOTUM, a negative regulator of canonical WNT signaling, was prominently expressed in first trimester EVT cells developing in situ and upregulated in EVT cells derived from human TS cells. Furthermore, NOTUM was required for human TS cell differentiation to EVT cells. Canonical WNT signaling is essential for maintaining human trophoblast cell stemness and prevention of human TS cell differentiation. Downregulation of canonical WNT signaling via the actions of NOTUM is required for EVT cell differentiation.
2024-03-06 | GSE206035 | GEO
Project description:Embryonic stem (ES) cells and trophoblast stem (TS) cells are both derived from early embryos, yet these cells have distinct differentiation properties. ES cells can differentiate into all three germ layer cell types, whereas TS cells can only differentiate into placental cells. It has not been determined whether TS cells can be converted into ES-like pluripotent stem (PS) cells. Here we report that overexpression of a single transcription factor, Oct4, in TS cells is sufficient to convert TS cells into a pluripotent state. These Oct4 induced pluripotent stem (OiPS) cells have the epigenetic characteristics of ES cells, including X chromosome reactivation and elevated H3K27 me3 modifications. The gene expression profile of OiPS cells and ES cells was very similar. Moreover, OiPS cells can differentiate into the three germ layer cell types in vitro and in vivo. More importantly, chimeric mice with germline transmission could be efficiently produced from OiPS cells. To our knowledge, this is the first evidence showing that only one single transcription factor could convert the non-embryonic TS cells into pluripotent stem cells with pluripotency. Gene expression profile of iPS cells and trophoblast stem cells were generated by Affymetrix Mouse Gene 1.0 ST Array. The Gene expression profile of ES cell R1 in GSE17004 was used as control. Three biological repeats were included for each line.
2010-11-12 | E-GEOD-25255 | biostudies-arrayexpress
Project description:Placental trophoblasts are key determinants of in utero development. Mouse trophoblast stem cells (mTSCs), which were first derived over a decade ago, are a powerful cell culture model for studying their self-renewal or differentiation. Our attempts to isolate an equivalent population from the trophectoderm of human blastocysts generated colonies that quickly differentiated in vitro. This finding suggested that the human placenta has another progenitor niche. Here we show that the chorion is one such site. Initially, we immunolocalized pluripotency factors and trophoblast fate determinants in the early-gestation placenta, amnion and chorion. Immunoreactive cells were numerous in the chorion. We isolated these cells and plated them in medium containing FGF and an inhibitor of activin/nodal signaling, which is required for human embryonic SC self-renewal. Colonies of polarized cells with a limited lifespan emerged. Trypsin dissociation yielded continuously self-replicating monolayers. Colonies and monolayers formed the two major human trophoblast lineages—multinucleate syncytiotrophoblasts and invasive cytotrophoblasts (CTBs). Transcriptional profiling experiments revealed the factors associated with the self-renewal or differentiation of human chorionic trophoblast progenitor cells (TBPCs). They included imprinted genes, NR2F1/2, HMGA2 and adhesion molecules that were required for TBPC differentiation. Together, the results of these experiments suggested that the chorion is one source of epithelial CTB progenitors. These findings explain why CTBs of fully formed chorionic villi have a modest mitotic index and identify the chorionic mesoderm as a niche for TBPCs that support placental growth. TBPC colonies (3 biological replicates), TPBC monolayers (2 biological replicates), CTB (3 biological replicates), hESC (3 biological replicates)
2011-06-22 | E-GEOD-30127 | biostudies-arrayexpress
Project description:Trophoblast is the primary epithelial cell type in the placenta, a transient organ required for proper fetal growth and development. We have identified a CDX2+/p63+ cytotrophoblast (CTB) subpopulation in the early post-implantation human placenta, which is significantly reduced later in gestation. CTB differentiate into different trophoblast subtypes, which are responsible for gas/nutrient exchange (syncytiotrophoblast/STB) and invasion and maternal vascular remodeling (extravillous trophoblast/EVT). Study of early human placental development is severely hampered by lack of a representative trophoblast stem cell (TSC) model, with the capacity for self-renewal and the ability to differentiate into both STB and EVT. We describe a reproducible protocol, using defined media containing BMP4, by which human embryonic stem cells (hESC) can be differentiated into CDX2+/p63+ CTB-like cells. These cells can be replated to further differentiate into STB- and EVT-like cells, based on marker expression, hormone secretion and invasive ability. Differentiation of hPSC-derived CTB in hypoxia leads to reduced hCG secretion and STB-associated gene expression, instead inducing EVT differentiation in a hypoxia-inducible factor-dependent manner.
2016-06-16 | GSE76090 | GEO
Project description:The human placenta (the extra-embryonic organ in which the fetus is made) is essential for conception and protection of the fetus during pregnancy. Extravillous trophoblasts (EVT) from placental villi infiltrate the decidua and convert maternal arteries into high-conductance vessels. Defects in trophoblast invasion and arterial conversion in early pregnancy are at the root of common pregnancy disorders such as preeclampsia. Here, we generated ecdysone and chorionic monocytic profiles across different gestational weeks spanning the 22-45 year age range, which allowed us to resolve the differentiation trajectory of trophoblast cells at implantation and its relationship with maternal age. We used this age atlas to identify age nodes of placental implantation change, revealing patterns of EVT implantation in advanced versus normal maternal age. Our data provide a comprehensive analysis of post-bedding trophoblast cell differentiation and may inform the design of experimental models of the placenta in early human pregnancy.
2025-09-02 | GSE240922 | GEO
Project description:Zika virus (ZIKV) infection at the maternal-placental interface is associated with adverse pregnancy outcomes including fetal demise and pregnancy loss. To determine how infection impacts placental trophoblasts, we utilized rhesus macaque trophoblast stem cells (TSC) that can be differentiated into early gestation syncytiotrophoblasts (ST) and extravillous trophoblasts (EVT). TSCs and STs, but not EVTs, were highly permissive to productive infection with ZIKV strain DAK AR 41524. The impact of ZIKV on the cellular transcriptome showed that infection of TSCs and STs increased expression of immune related genes, including those involved in type I and type III interferon responses. ZIKV exposure altered extracellular vesicle (EV) protein, mRNA, and miRNA cargo, regardless of productive infection. These findings suggest that early gestation macaque TSCs and STs are permissive to ZIKV infection, and that EV analysis may provide a foundation for identifying non-invasive biomarkers of placental infection in a highly translational model.
2022-05-20 | PXD033289 | Pride
Project description:We used trophoblast organoids differentiating to extravillous trophoblast (EVT) to study the effects of key cytokines secreted by uterine Natural Killer (uNK) cells on EVT behaviour. Specifically, we exposed the organoids to four uNK-derived cytokines (CSF1, CSF2, XCL1, CCL5) and collected cells at different time points along the EVT differentiation pathway for scRNA-seq. We observe enhanced EVT differentiation in cytokine-treated organoids demonstrated by the increased proportion of late EVT subtypes and regulation of related pathways such as epithelial-mesenchymal transition. Moreover, uNK cytokines affect other processes important during early pregnancy including dampening of inflammatory and adaptive immune responses, regulation of blood flow, and placental access to nutrients.
2024-01-10 | E-MTAB-13382 | biostudies-arrayexpress