Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ISRIB can temporarily maintain the cell fate of human trophoblast stem cell without activating WNT and inhibiting TGFβ

ABSTRACT: To investigate the role of ISRIB in human trophoblast stem cell(hTSC) maintenance without activation of WNT & TGFβ. We performed gene expression profiling analysis using data obtained from RNA-seq of hTSCs cultured in the medium contained 0.5 µM ISRIB and 10 µM Y27652, after removing CHIR99021, A83-01, SB431542.

ORGANISM(S): Homo sapiens

PROVIDER: GSE221409 | GEO | 2023/12/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Derivation of human trophoblast stem cells from placentas at birth

Project description:Human trophoblast stem cells (hTSCs) have emerged as a powerful tool for modeling the placental cytotrophoblast (CTB) in vitro. hTSCs were originally derived from CTBs of the first trimester or blastocyst-stage embryos in trophoblast stem cell medium (TSCM) that contains epidermal growth factor (EGF), the glycogen synthase kinase-beta (GSK3b) inhibitor CHIR99021, the transforming growth factor-beta (TGFb) inhibitors A83-01 and SB431542, valproic acid (VPA), and the Rho-associated protein kinase (ROCK) inhibitor Y27632. Here we show that hTSCs can be derived from CTBs isolated from the term placenta, using TSCM supplemented with a low concentration of mitochondrial pyruvate uptake inhibitor UK5099 and lipid-rich albumin (TUA medium). Notably, hTSCs could not be derived from term CTBs using TSCM alone, or in the absence of either UK5099 or lipid-rich albumin. Strikingly, hTSCs cultured in TUA medium for a few passages could be transitioned into TSCM and cultured thereafter in TSCM. hTSCs from term CTBs cultured in TUA medium as well as those transitioned into and cultured in TSCM thereafter could be differentiated to the extravillous trophoblast and syncytiotrophoblast lineages, and exhibited high transcriptome similarity with hTSCs derived from first trimester CTBs. We anticipate that these results will enable facile derivation of hTSCs from normal and pathological placentas at birth with diverse genetic backgrounds, and facilitate in vitro mechanistic studies in trophoblast biology.

2024-05-09 | GSE267112 | GEO

The Small Molecule ISRIB Reverses the Effects of eIF2α Phosphorylation on Translation and Stress Granule Assembly

Project description:We recently identified ISRIB as a potent inhibitor of the integrated stress response (ISR). ISRIB renders cells resistant to the effects of eIF2α phosphorylation and enhances long-term memory in rodents (10.7554/eLife.00498). Here we show by genome-wide in vivo ribosome profiling that translation of a restricted subset of mRNAs is induced upon ISR activation. ISRIB substantially reversed the translational effects elicited by phosphorylation of eIF2α and induced no major changes in translation or mRNA levels in unstressed cells. eIF2α phosphorylation-induced stress granule (SG) formation was blocked by ISRIB. Strikingly, ISRIB addition to stressed cells with pre-formed SGs induced their rapid disassembly, liberating mRNAs into the actively translating pool. Restoration of mRNA translation and modulation of SG dynamics may be an effective treatment of neurodegenerative diseases characterized by eIF2α phosphorylation, SG formation and cognitive loss. Ribosome profiling with paired RNA-seq

2015-02-27 | E-GEOD-65778 | biostudies-arrayexpress

The Small Molecule ISRIB Reverses the Effects of eIF2α Phosphorylation on Translation and Stress Granule Assembly

2015-02-27 | GSE65778 | GEO

ISRIB can temporarily maintain the cell fate of human trophoblast stem cell without activating WNT and inhibiting TGFβ

Project description:ISRIB can temporarily maintain the cell fate of human trophoblast stem cell without activating WNT and inhibiting TGFβ

| PRJNA914260 | ENA

Zika virus targets human trophoblast stem cells and prevents syncytialization in placental trophoblast organoids

Project description:Zika virus (ZIKV) infection during pregnancy results in an increased risk of spontaneous abortion and vertical transmission across placenta results in severe congenital defects in newborns. While the infectivity and pathological effects of ZIKV on the placental trophoblast progenitor cells in early human embryos remains largely unknown. Here, using the human trophoblast stem cells (hTSCs) isolated from human blastocyst, we showed that hTSCs were permissive to ZIKV infection, while resistance to ZIKV increased with differentiation. Combined CRISPR/Cas9-mediated gene knockout and RNA-seq assays, we demonstrated that the intrinsic expression of AXL and TIM-1, as well as the absence of potent interferon (IFN)-stimulated genes (ISGs), contributed to the high sensitivity of hTSCs to ZIKV. Furthermore, using our newly developed hTSC-derived 3 dimensional (3D) placental trophoblast organoid model, we demonstrated that ZIKV infection completely disrupted the structure of mature hTSC-organoids and inhibited syncytialization. Overall, our results clearly demonstrated that hTSCs represented the major target cells of ZIKV, and a possible reduced syncytialization may result from ZIKV infection of early developing placenta. These findings deepened our understanding of the characteristics and consequences of ZIKV infection of trophoblast stem cells in early human embryo.

2023-08-03 | GSE229702 | GEO

A genome-wide CRISPR-Cas9 knockout screen identifies essential and growth-restricting genes in human trophoblast stem cells

Project description:The recent derivation of bona fide human trophoblast stem cells (hTSCs) significantly improved our ability to study human placental biology and pathologies, but few studies have investigated the molecular regulators of hTSC identity. Therefore, we utilized a genome-wide CRISPR-Cas9 knockout screen to comprehensively define genes essential for or restricting the fitness of hTSCs. The resulting essential and growth-restricting genes include both well-established and potentially novel trophoblast regulators. We referenced our data to those of similar genetic screens performed in cancer cell lines and primed human pluripotent stem cells (hPSCs), as well as gene expression data of the early human embryos, to identify potential hTSC-specific and -enriched regulators. Among those are TEAD1, a gene previously reported to be dispensable for mouse placentation6. However, in the human trophoblast context, TEAD1 targets many hTSC regulators and plays a major role in its specification and maintenance. Overall, our study presents the first CRISPR/Cas9 knockout screen in a human extraembryonic lineage and provides a valuable resource for future trophoblast research.

2022-04-11 | GSE172329 | GEO

Long-term maintenance of functional primary human hepatocytes using small molecules

Project description:Primary human hepatocytes (PHHs) were cultured with or without a cocktail of four small molecules, Y-27632, PD0325901, A83-01 and CHIR99021 (termed YPAC), and their transcriptomes after a long-trm culture were compared.

2019-09-01 | GSE135011 | GEO

Rapid induction and long-term self-renewal of primitive neural precursors from human embryonic stem cells by small molecule inhibitors

Project description:Here, we report synergistic inhibition of glycogen synthase kinase 3 (GSK3), transforming growth factor β (TGF β), and Notch signaling pathways by small molecules can efficiently convert monolayer cultured hESCs into homogenous primitive neuroepithelium within one week under chemically defined condition. These primitive neuroepithelia can stably self-renew in the presence of leukemia inhibitory factor, GSK3 inhibitor (CHIR99021) and TGF β receptor inhibitor (SB431542); retain high neurogenic potential and responsiveness to instructive neural patterning cues toward midbrain and hindbrain neuronal subtypes; and exhibit in vivo integration. hESCs at about 20% confluence were treated with 3 μM CHIR99021, 2 μM SB431542, 0.1 μM Compound E (γ-Secretase Inhibitor XXI) in neural induction media containing Advanced DMEM/F12:Neurobasal (1:1), 1xN2, 1xB27, 1% Glutmax, 5 μg/ml BSA and 10 ng/ml hLIF, for 7 days. The culture was then split 1:3 for the next six passages using Accutase and cultured in neural induction media supplemented with 3 μM CHIR99021 and 2 μM SB431542 on X-ray inactivated MEF feeders or Matrigel-coated plates. After six passages, the cells were split 1:10 regularly.

2011-04-28 | GSE28595 | GEO

Molecular effects of ISRIB during asparagine deprivation

Project description:Molecular effects of ISRIB during asparagine deprivation

| PRJNA521363 | ENA

Rapid induction and long-term self-renewal of primitive neural precursors from human embryonic stem cells by small molecule inhibitors

2011-04-28 | E-GEOD-28595 | biostudies-arrayexpress