Elevated p53 Activities Restrict Differentiation Potential of MicroRNA-Deficient Pluripotent Stem Cells

Liu, Zhong; Zhang, Cheng; Skamagki, Maria; Khodadadi‐Jamayran, Alireza; Zhang, Wei; Kong, Dexin; Chang, Chia Wei; Feng, Jing; Han, Xiaosi; Townes, Tim M.; Li, Hu; Kim, Kitai; Zhao, Rui

doi:10.1016/j.stemcr.2017.10.006

Cited by 15 publications

(10 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Teratoma formation assay was performed as described [20,27]. In brief, 2−5×10 6 iPSCs were suspended in 100 μl of DMEM/F12 medium containing 30% of human ESC-qualified Geltrex membrane matrix (Thermo Fisher) and injected subcutaneously into 4–6 week-old NOD scid gamma (NSG) mice (005557, Jackson Laboratory).…”

Section: Methodsmentioning

confidence: 99%

“…All experiments involving lab animals were conducted in accordance with guidelines from the University of Alabama at Birmingham (UAB) and National Institute of Health. Teratoma formation assay was performed as described [20,27]. In brief, 2−5×10 6 iPSCs were suspended in 100 μl of DMEM/F12 medium containing 30% of human ESC-qualified Geltrex membrane matrix (Thermo Fisher) and injected subcutaneously into 4–6 week-old NOD scid gamma (NSG) mice (005557, Jackson Laboratory).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of iPSCs derived from low grade gliomas revealed early regional chromosomal amplifications during gliomagenesis

et al. 2018

Self Cite

View full text Add to dashboard Cite

Introduction. IDH1 mutation has been identified as a early genetic event driving low grade gliomas (LGGs) and it has been proven to exerts a powerful epigenetic effect. Cells containing IDH1 mutation are refractory to epigenetical reprogramming to iPSC induced by expression of Yamanaka transcription factors, a feature that we employed to study early genetic amplifications or deletions in gliomagenesis. Methods. We made iPSC clones from freshly surgically resected IDH1 mutant LGGs by forced expression of Yamanaka transcription factors. We sequenced the IDH locus and analyzed the genetic composition of multiple iPSC clones by array-based comparative genomic hybridization (aCGH). Results. We hypothesize that the primary cell pool isolated from LGG tumor contains a heterogeneous population consisting tumor cells at various stages of tumor progression including cells with early genetic lesions if any prior to acquisition of IDH1 mutation. Because cells containing IDH1 mutation are refractory to reprogramming, we predict that iPSC clones should originate only from LGG cells without IDH1 mutation, i.e. cells prior to acquisition of IDH1 mutation. As expected, we found that none of the iPSC clones contains IDH1 mutation. Further analysis by aCGH of the iPCS clones reveals that they contain regional chromosomal amplifications which are also present in the primary LGG cells. Conclusions. These results indicate that there exists a subpopulation of cells harboring gene amplification but without IDH1 mutation in the LGG primary cell pool. Further analysis of TCGA LGG database demonstrates that these regional chromosomal amplifications are also present in some cases of low grade gliomas indicating they are reoccurring lesions in glioma albeit at a low frequency. Taken together, these data suggest that regional chromosomal alterations may exist prior to the acquisition of IDH mutations in at least some cases of LGGs.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Characterization of iPSCs derived from low grade gliomas revealed early regional chromosomal amplifications during gliomagenesis

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…By suppressing both the CDK2 and CCND‐CDK4/6 cell cycle pathways, this cluster can regulate iPSC tumorigenicity during the G 1 ‐S phase transition . Moreover, some researchers have found that differentiation ability can be inhibited by elevated p53 activity in miRNA‐deficient iPSCs . Interestingly, miR‐302 can repress the expression of NR2F2 , a target gene verified by reporter luciferase assays and RT‐PCR, and stimulate the expression of OCT4 to promote cell pluripotency …”

Section: Regulatory Role and Mechanisms Of Mir‐302/367 Cluster Regardmentioning

confidence: 99%

Application of the microRNA‐302/367 cluster in cancer therapy

Liu

Wang

et al. 2020

Cancer Science

View full text Add to dashboard Cite

This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. , glycogen synthase kinase-3β; HCC, hepatocellular carcinoma; HECC, human endometrial carcinoma cell; hESC, human embryonic stem cell; IGF-1R, insulin-like growth factor 1 receptor; iPSCs, induced pluripotent stem cells; JNK, c-Jun NH2-terminal kinase; KLF4, Kruppel Like Factor 4; KPNA2, NF-κB-inducing kinase and karyopherin α2; LATS2, large tumor suppressor kinase 2; lncRNA, long noncoding RNA; LSCC, laryngeal squamous cell carcinoma; Mcl-1, myeloid cell leukemia sequence 1; MIAT, myocardial infarction-associated transcript; miRNA, microRNA; mirPS, miRNA-induced pluripotent stem; MTDH, metadherin; ncRNA, noncoding RNA; NK, natural killer; Notch4, notch receptor 4; NR2F2, nuclear receptor subfamily 2 group F member 2; OC, ovarian cancer; OCT, organic cation/carnitine transporter; PCa, prostate cancer; P-gp, P-glycoprotein; PRP-1, proline-rich polypeptide 1; RACK1, receptor for activated C-kinase 1; S1pr1, sphingosine-1-phosphate receptor 1; SDC1, syndecan 1; SDF1, stromal cell-derived factor 1; SHH, sonic hedgehog; SOX2, SRY-box transcription factor 2; Tcf3, transcription factor 3; SSEA-4, stage-specific embryonic antigen-4; YAP, Yes-associated transcriptional regulator. AbstractAs a novel class of noncoding RNAs, microRNAs (miRNAs) can effectively silence their target genes at the posttranscriptional level. Various biological processes, such as cell proliferation, differentiation, and motility, are regulated by miRNAs. In different diseases and different stages of disease, miRNAs have various expression patterns, which makes them candidate prognostic markers and therapeutic targets.Abnormal miRNA expression has been detected in numerous neoplastic diseases in humans, which indicates the potential role of miRNAs in tumorigenesis. Previous studies have indicated that miRNAs are involved in nearly the entire process of tumor development. MicroRNA-302a, miR-302b, miR-302c, miR-302d, and miR-367 are members of the miR-302/367 cluster that plays various biological roles in diverse neoplastic diseases by targeting different genes. These miRNAs have been implicated in several unique characteristics of cancer, including the evasion of growth suppressors, the sustained activation of proliferative signaling, the evasion of cell death and senescence, and the regulation of angiogenesis, invasion, and metastasis.This review provides a critical overview of miR-302/367 cluster dysregulation and the subsequent effects in cancer and highlights the vast potential of members of this cluster as therapeutic targets and novel biomarkers. K E Y W O R D Sbiological phenomena, cell dedifferentiation, MIRN302, neoplasm, therapy

show abstract

“…34 In mouse iPSCs, p53 accumulation was shown to cause impaired neural differentiation, which was successfully overcome by p53 inactivation. 35 In summary, our findings suggest that augmented p53 signaling is the common process underlying HUWE1-promoted XLID syndromes. Our previous work showed that depending on the type of HUWE1 mutation, its stability and activity are differentially affected, which in turn can have specific impacts on p53 levels.…”

Section: Discussionmentioning

confidence: 64%

Increased p53 signaling impairs neural differentiation in HUWE1-promoted intellectual disabilities

Aprigliano

Aksu

Bradamante

et al. 2021

Cell Reports Medicine

View full text Add to dashboard Cite

Increased p53 signaling impairs neural differentiation in HUWE1-promoted intellectual disabilitiesGraphical abstract Highlights d p53 signaling is hyperactivated in HUWE1-promoted intellectual disabilities d Neural differentiation is impaired in Juberg-Marsidi syndrome with HUWE1 p.G4310R d Juberg-Marsidi brain organoids have reduced size and aberrant cellular organization d Restored p53 signaling rescues neural development in Juberg-Marsidi syndrome

show abstract

Elevated p53 Activities Restrict Differentiation Potential of MicroRNA-Deficient Pluripotent Stem Cells

Cited by 15 publications

References 76 publications

Characterization of iPSCs derived from low grade gliomas revealed early regional chromosomal amplifications during gliomagenesis

Characterization of iPSCs derived from low grade gliomas revealed early regional chromosomal amplifications during gliomagenesis

Application of the microRNA‐302/367 cluster in cancer therapy

Increased p53 signaling impairs neural differentiation in HUWE1-promoted intellectual disabilities

Contact Info

Product

Resources

About