Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Patient specific iPSC-based model of Hydatidiform mole reveals abnormal BMP4 signaling caused by NLRP7 deficiency

ABSTRACT: Complete Hydatidiform Mole (HM) is a gestational trophoblastic disease resulting in hyper proliferation of trophoblast cells and absence of embryo development. Mutations in NLRP7 gene is a major cause of familial recurrent complete HM, where no embryonic tissue is present during the pregnancy. NLRP7 is a novel protein and its function is poorly understood. Lack of NLRP7 in the mouse genome and challenges in studying human embryogenesis as well as human trophoblast differentiation has prevented elucidation of the pathophysiology of this disease and the function of NLRP7 in HM. Here, we established an in vitro model of HM using NLRP7 deficient patient-derived human induced pluripotent stem cells (iPSCs). Whole transcriptome profiling during trophoblast differentiation revealed that NLRP7 deficiency results in precocious downregulation of pluripotency factors, activation of trophoblast genes and promotes maturation of differentiated extraembryonic cell types such as syncytiotrophoblasts. We further showed that these phenotypes are dependent on BMP4 signaling and BMP pathway inhibition prevented excessive trophoblast differentiation of HM-iPSCs. Taken together, this novel human iPSC model of a genetic placental disease recapitulates aspect of trophoblast biology and sheds light on early human embryogenesis by identifying NLRP7 as an important regulator of this process.

ORGANISM(S): Homo sapiens

PROVIDER: GSE125592 | GEO | 2021/09/09

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

1H NMR metabolite monitoring during the differentiation of human induced pluripotent stem cells provides new insights into the molecular events that regulate embryonic chondrogenesis

Project description:The integration of cell metabolism with signalling pathways, transcription factor networks and epigenetic mediators is critical in coordinating molecular and cellular events during embryogenesis. Induced pluripotent stem cells (IPSCs) are an established model for embryogenesis, germ layer specification and cell lineage differentiation, advancing the study of human embryonic development and the translation of innovations in drug discovery, disease modelling and cell-based therapies. The metabolic regulation of IPSC pluripotency is mediated by balancing glycolysis and oxidative phosphorylation, but there is a paucity of data regarding the influence of individual metabolite changes during cell lineage differentiation. We used <sup>1</sup>H NMR metabolite fingerprinting and footprinting to monitor metabolite levels as IPSCs are directed in a three-stage protocol through primitive streak/mesendoderm, mesoderm and chondrogenic populations. Metabolite changes were associated with central metabolism, with aerobic glycolysis predominant in IPSC, elevated oxidative phosphorylation during differentiation and fatty acid oxidation and ketone body use in chondrogenic cells. Metabolites were also implicated in the epigenetic regulation of pluripotency, cell signalling and biosynthetic pathways. Our results show that <sup>1</sup>H NMR metabolomics is an effective tool for monitoring metabolite changes during the differentiation of pluripotent cells with implications on optimising media and environmental parameters for the study of embryogenesis and translational applications.

2023-05-24 | MTBLS4854 | MetaboLights

Genome-wide DNA methylation analysis of diploid hydatidiform moles with androgenetic or biparental genomic origin

Project description:Only very few studies have investigated methylation patterns of different types of hydatidiform moles (HMs). Methylation patterns of androgenetic HMs (AnHMs) are abnormal due to the fact that the nuclear genome in AnHMs is inherited from the father, only. Diploid biparental HMs (BiHM) have been suggested to display the same methylation patterns of imprinted genes as AnHMs, and the methylation patterns are suspected to be a consequence of a failure to establish maternal methylation at multiple genome-wide loci. We have investigated the methylation patterns of AnHMs, BiHM-like placentas with a chr. 11p15.5 deletion and a BiHM from a woman with NLRP7 mutations and compared these to methylation patterns of normal placentas. Using the Next Generation Sequencing (NGS) technique Reduced Representation Bisulfite Sequencing (RRBS) we instigated the genome-wide CpG methylation of 32 samples, including nine normal placentas, 20 androgenetic diploid HMs (AnHMs), and three diploid biparental HMs/HM-like placentas. This dataset contains RRBS data from 12 samples, including the nine normal placentas and the three diploid biparental HMs/HM-like placentas.The RRBS data from 20 androgenetic diploid HMs (AnHMs) was deposited in GSE65881:http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65881

2015-06-01 | GSE67412 | GEO

Homo sapiens

Project description:NLRP7 promotes trophoblast lineage differentiation, YY1 binding and alters CpG methylation

| PRJNA196136 | ENA

NLRP7 promotes trophoblast lineage differentiation, YY1 binding and alters CpG methylation

Project description:Genome wide DNA methylation profiling of hESC in the untransduced, scrambled control and with knockdown of NLRP7 in undifferentiated and BMP4 differentiated states using the Illumina HumanMethylation 450 BeadChip. Several genomic sites exhibit altered methylation upon knocking down NLRP7. Bisulphite converted DNA from 3 replicates of untransduced, scrambled control and NLRP7 knockdown in the undifferentiated and BMP differentiated groups were hybridised to the Illumina Human Methylation 450 Beadchip.

2013-11-04 | E-GEOD-45727 | biostudies-arrayexpress

EGAS00001004722-2-sc-2023-02-01T09:39:21Z - samples

Project description:This dataset is part of a study that aims to compare in vivo human trophoblast differentiation into EVTs to different in vitro trophoblast organoids using single-cell and single-nuclei RNA sequencing. This specific dataset includes scRNA-seq and snRNA-seq data from trophoblast stem cells (TSCs). Trophoblast stem cell (TSC) lines BTS5 and BTS11 derived by Okae and colleagues were grown as described previously (Okae et al. 2018) together with EVT differentiation media. This study shows that the main regulatory programs mediating EVT invasion in vivo are preserved in in vitro models of EVT differentiation from primary trophoblast organoids and trophoblast stem cells. Data for primary trophoblast organoids is available under E-MTAB-12650.

| EGAD00001010017 | EGA

Human embryo and trophoblast proteome

Project description:Comprehensive quantitative proteomic study of human pre-implantation embryo stages reveal dynamic proteome landscape from M2, 8-cell and blastocyst stage, and during trophoblast stem cell (TS) differentiation. Identified key factors in early human embryos and lineage-specific trophoblast proteome profiles, correlated with transcriptomic analyses. This direct proteomic analysis provides a comprehensive analysis of the dynamic protein expression in human embryos during pre-implantation development and a powerful resource to enable further mechanistic studies on human trophoblast development and function.

2023-07-05 | MSV000092349 | MassIVE

Extensive Nuclear Reprogramming Underlies Lineage Conversion into Functional Trophoblast Stem-like Cells

Project description:The generation of induced pluripotent stem cells (iPSCs) and the direct conversion approach provide an invaluable resource of cells for disease modeling, drug screening, and patient-specific cell-based therapy. However, while iPSCs are stable and resemble ESCs in their transcriptome, methylome and function, the vast majority of the directly converted cells represent an incomplete reprogramming state as evident by their aberrant transcriptome and transgene dependency. This raises the question of whether complete and stable nuclear reprogramming can be achieved only in pluripotent cells. Here we demonstrate the generation of stable and fully functional induced trophoblast stem cells (iTSCs) by transient expression of Gata3, Tfap2c and Eomes. Similarly to iPSCs, iTSCs underwent a complete and stable reprogramming process as assessed by transcriptome and methylome analyses and functional assays such as the formation of hemorrhagic lesion and placenta contribution. Careful examination of the conversion process indicated that the cells did not go through a transient pluripotent state. These results suggest that complete nuclear reprograming can be attained in non-pluripotent cells.

2015-10-01 | GSE64684 | GEO

Naïve-like pluripotency to pave the way for saving the northern white rhinoceros from extinction

Project description:The northern white rhinoceros (NWR) is probably the earth’s most endangered mammal. To rescue the functionally extinct species, we aim to employ induced pluripotent stem cells (iPSCs) to generate gametes and subsequently embryos in vitro. To elucidate the regulation of pluripotency and differentiation of NWR PSCs, we generated iPSCs from a deceased NWR female using episomal reprogramming, and observed surprising similarities to human PSCs. NWR iPSCs exhibit a broad differentiation potency into the three germ layers and trophoblast, and acquire a naïve-like state of pluripotency, which is pivotal to differentiate PSCs into primordial germ cells (PGCs). Naïve culturing conditions induced a similar expression profile of pluripotency related genes in NWR iPSCs and human ESCs. Furthermore, naïve-like NWR iPSCs displayed increased expression of naïve and PGC marker genes, and a higher integration propensity into developing mouse embryos. As the conversion process was aided by ectopic BCL2 expression, and we observed integration of reprogramming factors, the NWR iPSCs presented here are unsuitable for gamete production. However, the gained insights into the developmental potential of both primed and naïve-like NWR iPSCs are fundamental for in future PGC-specification in order to rescue the species from extinction using cryopreserved somatic cells.

2021-12-01 | GSE161173 | GEO

scRNA-seq and snucRNA-seq of human primary trophoblast organoids (PTO) and trophoblast stem cells (TSCs) differentiation into extravillous trophoblast organoids (EVTs)

Project description:This study aims to compare in vivo human trophoblast differentiation into EVTs to different in vitro trophoblast organoids using single-cell and single-nuclei RNA sequencing. The study includes two type of systems: human primary trophoblast organoids (PTO) and trophoblast stem cells (TSCs). Trophoblast stem cell (TSC) lines BTS5 and BTS11 derived by Okae and colleagues were grown as described previously (Okae et al. 2018) and together with EVT media. Primary trophoblast organoids (PTO) were grown and differentiated into EVT as previously described by Turco & Sheridan (Turco et al 2018; Sheridan et al 2020). This study shows that the main regulatory programs mediating EVT invasion in vivo are preserved in in vitro models of EVT differentiation from primary trophoblast organoids and trophoblast stem cells.

2023-02-09 | E-MTAB-12650 | biostudies-arrayexpress

Examining serotonergic neuron differentiation from human iPSCs

Project description:Examining serotonergic neuron differentiation from human iPSCs

| PRJNA483556 | ENA