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Modeling Preeclampsia using human induced pluripotent stem cells [methylation]

ABSTRACT: Modeling Preeclampsia using human induced pluripotent stem cells [methylation]

PROVIDER: PRJNA669029 | ENA |

REPOSITORIES: ENA

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Modeling Preeclampsia using human induced pluripotent stem cells

Project description:Modeling Preeclampsia using human induced pluripotent stem cells

| PRJNA669030 | ENA

Modeling Preeclampsia using human induced pluripotent stem cells [RNA-seq]

Project description:Modeling Preeclampsia using human induced pluripotent stem cells [RNA-seq]

| PRJNA668942 | ENA

Modeling Preeclampsia using human induced pluripotent stem cells [methylation]

Project description:Preeclampsia (PE) is a hypertensive disorder, which affects up to 10% of pregnancies worldwide. The primary etiology is considered to be abnormal development and function of placental cells called trophoblasts. We previously developed a two-step protocol for differentiation of human pluripotent stem cells, first into cytotrophoblast (CTB) progenitor-like cells, and then into both syncytiotrophoblast (STB)- and extravillous trophoblast (EVT)-like cells, and showed that this protocol can be used to model both normal and abnormal trophoblast differentiation. We have now applied this protocol to differentiate induced pluripotent stem cells (iPSC) derived from placentas of pregnancies with or without PE. While we did not note any differences in CTB induction, PE-iPSC-derived CTB showed a defect in syncytialization, and had a >180-fold reduction in expression of PSG4, a mature STB marker (p<0.02). While EVT formation did not appear to be altered, the invasive capacity of PE-iPSC-derived EVT was non-responsive to a decrease in oxygen tension, while that of non-PE-iPSC-derived EVT was enhanced 3.8-fold. RNA sequencing analysis showed gene expression changes consistent with defects in STB formation and response to hypoxia in PE-iPSC derived trophoblast. However, differences in DNA methylation were minimal, with only documented differences consistent with part of the response to hypoxia. Overall, PE-associated iPSC recapitulated multiple defects associated with placental dysfunction, with their lack of response to decreased oxygen tension emphasizing the importance of the interface with the maternal microenvironment in normal placentation.

2021-03-15 | GSE159479 | GEO

Modeling Preeclampsia using human induced pluripotent stem cells [RNA-seq]

2021-03-15 | GSE159437 | GEO

Modeling Preeclampsia using human induced pluripotent stem cells

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2021-03-15 | GSE159480 | GEO

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Modeling Alcohol-induced Neurotoxicity using Human Induced Pluripotent Stem Cell-derived Three-Dimensional Cerebral Organoids

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Human iPSC-based Modeling of Late-Onset Disease using Progerin-induced Aging

Project description:Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) sets their identity back to an embryonic age. This presents a fundamental hurdle for modeling late-onset disorders using iPSC-derived cells. We therefore developed a strategy to induce age-like features in multiple iPSC-derived lineages and tested its impact on modeling Parkinson’s disease (PD). We first describe markers that predict fibroblast donor age and observed the loss of these age-related markers following iPSC induction and re-differentiation into fibroblasts. Remarkably, age-related markers were readily induced in iPSC-derived fibroblasts or neurons following exposure to progerin including dopamine neuron-specific phenotypes such as neuromelanin accumulation. Induced aging in PD-iPSC-derived dopamine neurons revealed disease phenotypes requiring both aging and genetic susceptibility such as frank dendrite degeneration, progressive loss of tyrosine-hydroxylase expression and enlarged mitochondria or Lewy body-precursor inclusions. Our study presents a strategy for inducing age-related cellular properties and enables the modeling of late-onset disease features. Induced pluripotent stem cell-derived midbrain dopamine neurons from a young and old donor overexpressing either GFP or Progerin.

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In vitro modeling of human germ cell development using pluripotent stem cells

Project description:In vitro modeling of human germ cell development using pluripotent stem cells

| PRJNA427441 | ENA