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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Single cell RNA-sequencing experiment of human embryonic stem cells (hESCs) upon Wnt stimulation treatment at three time points (4 hours, 24 hours and 3 days)

ABSTRACT: Wnt/b-catenin signalling is an evolutionarily conserved mechanism for cell-cell communication implicated in both developmental processes and diseases such as cancer. A main part of this signalling pathway is the stabilization and nuclear translocation of b-catenin, driving the transcriptional regulation of target genes. However, while b-catenin target genes traditionally have been through to be collectively regulated upon Wnt pathway stimulation, this appears in contrast with the non-overlapping patterns of Wnt target gene expression in several contexts, including early mammalian embryogenesis. To address the question whether individual cells exhibits diverse responses to Wnt stimulation, we followed Wnt target gene activation in human embryonic stem cells (hESCs) via single cell RNA-sequencing (scRNAseq) after GSK3 inhibition at 4, 24 and 72 hours of stimulation.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Homo sapiens

SUBMITTER: Claudio Cantù

PROVIDER: E-MTAB-12598 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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ATAC-seq experiment at four time points in HEK293 and hESC cells, assessing the time-resolved response on chromatin accessibility upon Wnt/β-catenin signaling activation

Project description:Wnt/β-catenin signaling is a highly organized biochemical cascade that triggers a gene expression program in the signal-receiving cell. The Wnt/β-catenin -driven transcriptional response is involved in virtually all cellular processes during development, homeostasis, and its deregulation causes human disease. However, outstanding questions remain unanswered. Among these, one regards how the Wnt/β-catenin cascade modulates the chromatin behavior: to date, there exists no comprehensive genome-wide annotation of changing chromatin patterns upon Wnt pathway activation. This is important, as shifts in chromatin patterns might underlie how different cells promote diverging gene expression programs in response to Wnt. To address this question, we characterized how Wnt/β-catenin signaling shapes the genome-wide chromatin accessibility landscape in two human cell types, human embryonic kidney cells 293T (HEK293T) and human embryonic stem cells (hESCs), over time. To this end, we treated HEK293T and hESCs with the GSK3 inhibitor/Wnt activator CHIR99021 (10 mM) for 3 days and assessed chromatin accessibility via ATAC-sequencing 4 hours, 24 hours and 3 days after the onset of the stimulation. We found that hESCs respond to Wnt/β-catenin activation by progressively shaping their chromatin accessibility profile in a manner that is consistent with their gradual acquisition of a mesodermal identity: differentiation genes loci open over time, while pluripotency ones close. We refer to this genomic response as plastic. On the other hand, HEK293T, which are known to be highly responsive to Wnt activation, appear more resistant to a long-term Wnt/β-catenin-driven change in cell identity. In this context, the chromatin displays a temporary opening of relevant regions at 4 hours after stimulation, followed by a re-establishment of its pre-stimulation state: we define this transient response as elastic.

2022-09-30 | E-MTAB-12076 | biostudies-arrayexpress

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2022-09-30 | E-MTAB-12077 | biostudies-arrayexpress

RNA-seq experiment at four time points in HEK293 and hESC cells, assessing the time-resolved response on gene expression upon Wnt/β-catenin signaling activation

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2016-02-23 | E-GEOD-78159 | biostudies-arrayexpress

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2020-08-14 | PXD020478 | Pride

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2023-04-19 | PXD038811 | Pride

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2016-02-23 | GSE78159 | GEO

ChIP-seq analysis of M-NM-2-catenin in mouse embryonic stem cells treated with GSK3 inhibitor CHIR99021 under serum+LIF standard condition.

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