scholarly journals Zfp281 Shapes the Transcriptome of Trophoblast Stem Cells and Is Essential for Placental Development

Cell Reports ◽  
2019 ◽  
Vol 27 (6) ◽  
pp. 1742-1754.e6 ◽  
Author(s):  
Takashi Ishiuchi ◽  
Hiroaki Ohishi ◽  
Tetsuya Sato ◽  
Satoshi Kamimura ◽  
Masayoshi Yorino ◽  
...  
Keyword(s):  
Stem Cells ◽  
Placental Development ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem

scholarly journals Skp2 contributes to cell cycle progression in trophoblast stem cells and to placental development

2020 ◽  
Vol 25 (6) ◽  
pp. 427-438 ◽  
Author(s):  
Yuhei Yamauchi ◽  
Akihiro Nita ◽  
Masaaki Nishiyama ◽  
Yoshiharu Muto ◽  
Hideyuki Shimizu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Cycle Progression ◽  
Placental Development ◽  
Cycle Progression ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem

scholarly journals Connexin31-deficient trophoblast stem cells: a model to analyze the role of gap junction communication in mouse placental development

2004 ◽  
Vol 273 (1) ◽  
pp. 63-75 ◽  
Author(s):  
Mark Kibschull ◽  
Mariam Nassiry ◽  
Caroline Dunk ◽  
Alexandra Gellhaus ◽  
Jennifer A Quinn ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gap Junction ◽  
Placental Development ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem ◽  
Gap Junction Communication

scholarly journals Efficient derivation of human trophoblast stem cells from primed pluripotent stem cells

2021 ◽  
Vol 7 (33) ◽  
pp. eabf4416
Author(s):  
Yanxing Wei ◽  
Tianyu Wang ◽  
Lishi Ma ◽  
Yanqi Zhang ◽  
Yuan Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Chromatin Accessibility ◽  
Placental Development ◽  
Differentiation Potential ◽  
Human Trophoblast ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem ◽  
Early Placenta ◽  
And Function

Human trophoblast stem cells (hTSCs) provide a valuable model to study placental development and function. While primary hTSCs have been derived from embryos/early placenta, and transdifferentiated hTSCs from naïve human pluripotent stem cells (hPSCs), the generation of hTSCs from primed PSCs is problematic. We report the successful generation of TSCs from primed hPSCs and show that BMP4 substantially enhances this process. TSCs derived from primed hPSCs are similar to blastocyst-derived hTSCs in terms of morphology, proliferation, differentiation potential, and gene expression. We define the chromatin accessibility dynamics and histone modifications (H3K4me3/H3K27me3) that specify hPSC-derived TSCs. Consistent with low density of H3K27me3 in primed hPSC-derived hTSCs, we show that knockout of H3K27 methyltransferases (EZH1/2) increases the efficiency of hTSC derivation from primed hPSCs. Efficient derivation of hTSCs from primed hPSCs provides a simple and powerful model to understand human trophoblast development, including the pathogenesis of trophoblast-related disorders, by generating disease-specific hTSCs.

scholarly journals Isolation and characterisation of a novel trophoblast side-population from first trimester placentae

Reproduction ◽  
2015 ◽  
Vol 150 (5) ◽  
pp. 449-462 ◽  
Author(s):  
J L James ◽  
D G Hurley ◽  
T K J B Gamage ◽  
T Zhang ◽  
R Vather ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Side Population ◽  
First Trimester ◽  
Placental Development ◽  
Human Trophoblast ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem ◽  
Future Work ◽  
Extravillous Trophoblasts

The placenta is responsible for all nutrient and gas exchange between mother and baby during pregnancy. The differentiation of specialised placental epithelial cells called trophoblasts is essential for placental function, but we understand little about how these populations arise. Mouse trophoblast stem cells have allowed us to understand many of the factors that regulate murine trophoblast lineage development, but the human placenta is anatomically very different from the mouse, and it is imperative to isolate a human trophoblast stem cell to understand human placental development. Here we have developed a novel methodology to isolate a Hoechst side-population of trophoblasts from early gestation placentae and compared their transcriptome to differentiated trophoblast populations (cytotrophoblasts and extravillous trophoblasts) using microarray technology. Side-population trophoblasts clustered as a transcriptomically distinct population but were more closely related to cytotrophoblasts than extravillous trophoblasts. Side-population trophoblasts up-regulated a number of genes characteristic of trophectoderm and murine trophoblast stem cells in comparison to cytotrophoblasts or extravillous trophoblasts and could be distinguished from both of these more mature populations by a unique set of 22 up-regulated genes, which were enriched for morphogenesis and organ development and the regulation of growth functions. Cells expressing two of these genes (LAMA2 and COL6A3) were distributed throughout the cytotrophoblast layer at the trophoblast/mesenchymal interface. Comparisons to previously published trophoblast progenitor populations suggest that the side-population trophoblasts isolated in this work are a novel human trophoblast population. Future work will determine whether these cells exhibit functional progenitor/stem cell attributes.

scholarly journals Esrrb plays important roles in maintaining self-renewal of trophoblast stem cells (TSCs) and reprogramming somatic cells to induced TSCs

2018 ◽  
Vol 11 (6) ◽  
pp. 463-473 ◽  
Author(s):  
Haibo Gao ◽  
Rui Gao ◽  
Linfeng Zhang ◽  
Wenchao Xiu ◽  
Ruge Zang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Cell Model ◽  
Embryonic Stem ◽  
Placental Development ◽  
Self Renewal ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem

Abstract Trophoblast stem cells (TSCs), which can be derived from the trophoectoderm of a blastocyst, have the ability to sustain self-renewal and differentiate into various placental trophoblast cell types. Meanwhile, essential insights into the molecular mechanisms controlling the placental development can be gained by using TSCs as the cell model. Esrrb is a transcription factor that has been shown to play pivotal roles in both embryonic stem cell (ESC) and TSC, but the precise mechanism whereby Esrrb regulates TSC-specific transcriptome during differentiation and reprogramming is still largely unknown. In the present study, we elucidate the function of Esrrb in self-renewal and differentiation of TSCs, as well as during the induced TSC (iTSC) reprogramming. We demonstrate that the precise level of Esrrb is critical for stem state maintenance and further trophoblast differentiation of TSCs, as ectopically expressed Esrrb can partially block the rapid differentiation of TSCs in the absence of fibroblast growth factor 4. However, Esrrb depletion results in downregulation of certain key TSC-specific transcription factors, consequently causing a rapid differentiation of TSCs and these Esrrb-deficient TSCs lose the ability of hemorrhagic lesion formation in vivo. This function of Esrrb is exerted by directly binding and activating a core set of TSC-specific target genes including Cdx2, Eomes, Sox2, Fgfr4, and Bmp4. Furthermore, we show that Esrrb overexpression can facilitate the MEF-to-iTSC conversion. Moreover, Esrrb can substitute for Eomes to generate GEsTM-iTSCs. Thus, our findings provide a better understanding of the molecular mechanism of Esrrb in maintaining TSC self-renewal and during iTSC reprogramming.

scholarly journals The Impact of Hypoxia in Early Pregnancy on Placental Cells

2021 ◽  
Vol 22 (18) ◽  
pp. 9675
Author(s):  
Hui Zhao ◽  
Ronald J. Wong ◽  
David K. Stevenson
Keyword(s):  
Stem Cells ◽  
First Trimester ◽  
Low Oxygen ◽  
Placental Development ◽  
Trophoblast Stem Cells ◽  
Oxygen Levels ◽  
Trophoblast Stem ◽  
Adverse Pregnancy ◽  
And Function ◽  
The Impact

Oxygen levels in the placental microenvironment throughout gestation are not constant, with severe hypoxic conditions present during the first trimester. This hypoxic phase overlaps with the most critical stages of placental development, i.e., blastocyst implantation, cytotrophoblast invasion, and spiral artery remodeling initiation. Dysregulation of any of these steps in early gestation can result in pregnancy loss and/or adverse pregnancy outcomes. Hypoxia has been shown to regulate not only the self-renewal, proliferation, and differentiation of trophoblast stem cells and progenitor cells, but also the recruitment, phenotype, and function of maternal immune cells. In this review, we will summarize how oxygen levels in early placental development determine the survival, fate, and function of several important cell types, e.g., trophoblast stem cells, extravillous trophoblasts, syncytiotrophoblasts, uterine natural killer cells, Hofbauer cells, and decidual macrophages. We will also discuss the cellular mechanisms used to cope with low oxygen tensions, such as the induction of hypoxia-inducible factor (HIF) or mammalian target of rapamycin (mTOR) signals, regulation of the metabolic pathway, and adaptation to autophagy. Understanding the beneficial roles of hypoxia in early placental development will provide insights into the root cause(s) of some pregnancy disorders, such as spontaneous abortion, preeclampsia, and intrauterine growth restriction.

scholarly journals Characterization of primary models of human trophoblast

Development ◽  
2021 ◽  
Author(s):  
Megan A. Sheridan ◽  
Xiaohui Zhao ◽  
Ridma C. Fernando ◽  
Lucy Gardner ◽  
Vicente Perez-Garcia ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extravillous Trophoblast ◽  
Suitable Model ◽  
Placental Development ◽  
Human Trophoblast ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem

Although understanding of human placental development is still limited, two models, trophoblast organoids and trophoblast stem cells (TSC) provide new useful tools to study this. Both differentiate from villous cytotrophoblast (VCT) to either extravillous trophoblast (EVT) or syncytiotrophoblast (SCT). Here, we compare transcriptomes and miRNA profiles of these models to identify which trophoblast they resemble in vivo. Our findings indicate that TSC do not readily undergo SCT differentiation and closely resemble cells at the base of the cell columns from where EVT are derived. In contrast, organoids are similar to VCT and undergo spontaneous SCT differentiation. A defining feature of human trophoblast is that VCT and SCT are HLA null whilst EVT express HLA-C, -G, -E molecules. We find that trophoblast organoids retain these in vivo characteristics. In contrast, TSC do express classical HLA-A and HLA-B molecules and still maintain their expression after EVT differentiation with upregulation of HLA-G. Furthermore, HLA expression in TSC differs when grown in 3D rather than 2D suggesting mechanical cues are important. Our results will allow choice of the most suitable model to study trophoblast development, function and pathology.

scholarly journals MSX2 safeguards syncytiotrophoblast fate of human trophoblast stem cells

2021 ◽  
Author(s):  
Ruth Hornbachner ◽  
Andreas Lackner ◽  
Sandra Haider ◽  
Martin Knöfler ◽  
Karl Mechtler ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Placental Development ◽  
Human Trophoblast ◽  
Trophoblast Stem Cells ◽  
Cell Fate Decisions ◽  
Trophoblast Stem ◽  
And Function ◽  
Strong Interactors

AbstractThe majority of placental pathologies are associated with failures in trophoblast differentiation, yet the underlying transcriptional regulation is poorly understood. Here, we use human trophoblast stem cells to elucidate the function of the transcription factor MSX2 in trophoblast specification. We show that depletion of MSX2 de-represses the syncytiotrophoblast program, while forced expression of MSX2 blocks it. We demonstrate that a large proportion of the affected genes are directly bound and regulated by MSX2 and identify components of the SWI/SNF complex as its strong interactors. Our findings uncover the pivotal role of MSX2 in cell fate decisions that govern human placental development and function.

scholarly journals Trophoblast Stem Cells: Models for Investigating Trophectoderm Differentiation and Placental Development

2009 ◽  
Vol 30 (3) ◽  
pp. 228-240 ◽  
Author(s):  
Gordon C. Douglas ◽  
Catherine A. VandeVoort ◽  
Priyadarsini Kumar ◽  
Tien-Cheng Chang ◽  
Thaddeus G. Golos
Keyword(s):  
Stem Cells ◽  
Molecular Diversity ◽  
Diverse Populations ◽  
Future Prospects ◽  
Placental Development ◽  
Trophoblast Stem Cells ◽  
Experimental Systems ◽  
Trophoblast Stem ◽  
Shed Light ◽  
Maternal Decidua

Abstract The placenta is an ephemeral organ containing diverse populations of trophoblasts that are all derived from the embryonic trophectoderm but have morphological, functional, and molecular diversity within and across species. In hemochorial placentation, these cells play especially important roles, interfacing with and modifying the cells of the maternal decidua. Within the rapidly growing placenta, it has been shown that there are trophoblast stem cells well characterized in the mouse and postulated but not well understood in primates. This review will discuss the characteristics of candidates for human and nonhuman primate trophoblast stem cells, present the diverse methods of their generation, and propose future prospects for experimental systems in which they can shed light on developmental and pathophysiological processes in human pregnancy.

scholarly journals Human trophoblast stem cells: Real or not real?

Placenta ◽  
2017 ◽  
Vol 60 ◽  
pp. S57-S60 ◽  
Author(s):  
Ching-Wen Chang ◽  
Mana M. Parast
Keyword(s):  
Stem Cells ◽  
Human Trophoblast ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem
Sign in / Sign up

Export Citation Format

Share Document