Constitutive High Expression of NOXA Sensitizes Human Embryonic Stem Cells for Rapid Cell Death

Basundra, Richa; Kapoor, Sahil; Hollville, Émilie; Kiapour, Nazanin; Lopez, Adriana Beltran; Melchiorre, Nicole Marie; Deshmukh, Mohanish

doi:10.1093/stmcls/sxab008

Cited by 4 publications

(3 citation statements)

References 35 publications

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“…Our findings suggest that MCL-1 could regulate hPSC survival after exposure to 1% O 2 and that depending on the hypoxia inducer, alternative gene expression programs become operative in hPSCs. In line with our findings, it was demonstrated that high expression of NOXA sensitizes hPSCs for rapid cell death 53 . It is then conceivable that the decrease in the expression levels of MCL-1 triggered by 1% O 2 or the reduction of MCL-1/NOXA complexes due to S63845 treatment may turn hPSCs more susceptible to dye.…”

Section: Discussionsupporting

confidence: 91%

Acute severe hypoxia induces apoptosis of human pluripotent stem cells by a HIF-1α and P53 independent mechanism

Mucci

Isaja

Rodríguez-Varela

et al. 2022

Sci Rep

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Human embryonic and induced pluripotent stem cells are self-renewing pluripotent stem cells (hPSCs) that can differentiate into a wide range of specialized cells. Although moderate hypoxia (5% O2) improves hPSC self-renewal, pluripotency, and cell survival, the effect of acute severe hypoxia (1% O2) on hPSC viability is still not fully elucidated. In this sense, we explore the consequences of acute hypoxia on hPSC survival by culturing them under acute (maximum of 24 h) physical severe hypoxia (1% O2). After 24 h of hypoxia, we observed HIF-1α stabilization concomitant with a decrease in cell viability. We also observed an increase in the apoptotic rate (western blot analysis revealed activation of CASPASE-9, CASPASE-3, and PARP cleavage after hypoxia induction). Besides, siRNA-mediated downregulation of HIF-1α and P53 did not significantly alter hPSC apoptosis induced by hypoxia. Finally, the analysis of BCL-2 family protein expression levels disclosed a shift in the balance between pro- and anti-apoptotic proteins (evidenced by an increase in BAX/MCL-1 ratio) caused by hypoxia. We demonstrated that acute physical hypoxia reduced hPSC survival and triggered apoptosis by a HIF-1α and P53 independent mechanism.

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Section: Discussionsupporting

confidence: 91%

Acute severe hypoxia induces apoptosis of human pluripotent stem cells by a HIF-1α and P53 independent mechanism

Mucci

Isaja

Rodríguez-Varela

et al. 2022

Sci Rep

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“…PMAIP1 is essential for cell death in hESCs. It is highly expressed in pluripotent stem cells but decreases during neuronal differentiation and is controlled by POU5F1 (Basundra et al, 2022). SEPHS1 is essential for the survival of hESC.…”

Section: Resultsmentioning

confidence: 99%

Deciphering the mRNA-lncRNA-miRNA interaction landscape in human pluripotency

Ghosh

Som

2022

Preprint

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Human embryonic stem cells offer a huge potential for the study of early human development and for application in biomedical sciences. Growing evidence has shown that besides the protein coding genes, the non-coding elements of the human genome play a crucial role in maintaining its property of self renewal and in cell fate determination. However, a clear understanding of this regulatory mechanism and the landscape of interactions between the coding and non-coding elements was still lacking. To fill in this void, we use transcriptomic data from RNA-seq and small RNA-seq experiments to reconstruct the core pluripotency circuitry involving mRNAs, lncRNAs and miRNAs. The overall interaction landscape revealed an alternate circuit for the maintenance of pluripotency devoid of the classic pluripotency transcription factors NANOG, SOX2 and POU5F1. We also identified networks specific to the naive and primed states of human pluripotency revealing a new set of transcriptomic markers that could not only be used to differentiate pluripotent state from non-pluripotent state but also to identify the intra-pluripotency state. The lncRNA DANT1 was found to be crucial in determination to the two pluripotency states as it formed a bridge between the naive and primed state specific pluripotency networks. Further, we also identified and computationally validated putative ceRNA mechanism involving DANT1, the miRNAs hsa-miR-30c-2-3p, hsa-miR-210-3p and hsa-let-7b-5p, and several key pluripotency related genes including PTPRZ1, SALL2, TOX3, ZNF695, and ZYG11A which warrants further experimental validation.

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Section: Identification Of Hub Genes In Plurimlminetmentioning

confidence: 99%

Network analysis of transcriptomic data uncovers molecular signatures and the interplay of mRNAs, lncRNAs, and miRNAs in human embryonic stem cells

Ghosh,

Som

2023

Differentiation

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Constitutive High Expression of NOXA Sensitizes Human Embryonic Stem Cells for Rapid Cell Death

Cited by 4 publications

References 35 publications

Acute severe hypoxia induces apoptosis of human pluripotent stem cells by a HIF-1α and P53 independent mechanism

Acute severe hypoxia induces apoptosis of human pluripotent stem cells by a HIF-1α and P53 independent mechanism

Deciphering the mRNA-lncRNA-miRNA interaction landscape in human pluripotency

Network analysis of transcriptomic data uncovers molecular signatures and the interplay of mRNAs, lncRNAs, and miRNAs in human embryonic stem cells

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