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TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE168587 | GEO | 2022/02/15

REPOSITORIES: GEO

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TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling.

Project description:Aneuploidy, defective differentiation, and inactivation of the tumor suppressor TP53 all occur frequently during tumorigenesis. Here, we probe the potential links among these cancer traits by inactivating TP53 in human embryonic stem cells (hESCs). TP53-/- hESCs exhibit increased proliferation rates, mitotic errors, and low-grade structural aneuploidy; produce poorly differentiated immature teratomas in mice; and fail to differentiate into neural progenitor cells (NPCs) in vitro. Genome-wide CRISPR screen reveals requirements of ciliogenesis and sonic hedgehog (Shh) pathways for hESC differentiation into NPCs. TP53 deletion causes abnormal ciliogenesis in neural rosettes. In addition to restraining cell proliferation through CDKN1A, TP53 activates the transcription of BBS9, which encodes a ciliogenesis regulator required for proper Shh signaling and NPC formation. This developmentally regulated transcriptional program of TP53 promotes ciliogenesis, restrains Shh signaling, and commits hESCs to neural lineages.

| S-EPMC8904926 | biostudies-literature

TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling [RNA-Seq]

Project description:H9 WT ESCs or TP53 KO (Clone 1) ESCs were injected subcutaneously into mice for teratoma formation. 6-8 weeks later, teratomas were isolated and total RNA was purified. TruSeq library preparation kit from Illumina was used to make libraries for RNA-Seq. NGS sequencing on Illumina NextSeq 500 was performed and data was analyzed to determine changes in transcriptome between WT and TP53 KO teratoma cells.

2022-02-16 | GSE168678 | GEO

TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling [CRISPR screen]

Project description:CRISPR-Cas9 screen was done to identify genes required for NPC differentiation. Sox1 is an established NPC marker. Human ESCs were infected with GecKO v2 library, selected with puromycin and then allowed to differentiate into Neural progenitor cells (NPC) using StemDiff monolayer protocol (Stem cell Technologies). Day 7 NPCs were collected and FACS sorted to obtain bottom 1% of Sox1 expressing cells. NGS was used to identify guide sequences in cell population and determine the genes required for Sox1 expression during NPC differentiation.

2022-02-16 | GSE168585 | GEO

TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling [ChIP-seq]

Project description:NGS was used to analyze role of TP53 in differentiation of human embryonic stem cells. TP53, a transcription factor, binds DNA and regulates transcription of specific genes. Chipseq of TP53 was done on WT ESCs and NPCs to identify direct targets of TP53 during differentiation of hESCs into neuronal lineage.

2022-02-16 | GSE168584 | GEO

TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling [RNA-Seq 2]

Project description:NGS was used to analyze role of TP53 in differentiation of human embryonic stem cells. RNAseq and was done in WT and p53 KO embryonic stem cells (ESCs) and in in vitro differentiated Neural progenitor cells (NPCs).

2022-02-16 | GSE168752 | GEO

TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling

Project description:TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling

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TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling [ChIP-seq]

Project description:TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling [ChIP-seq]

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TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling [CRISPR screen]

Project description:TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling [CRISPR screen]

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TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling [RNA-Seq]

Project description:TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling [RNA-Seq]

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TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling [RNA-Seq 2]

Project description:TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling [RNA-Seq 2]

| PRJNA713815 | ENA