Expression of miRNAs from the Imprinted DLK1/DIO3 Locus Signals the Osteogenic Potential of Human Pluripotent Stem Cells

Barrault, Laetitia; Gide, Jacqueline; Qing, Tingting; Lesueur, Léa; Tost, Jörg; Denis, Jérôme Alexandre; Cailleret, Michel; Aubry, Laëtitia; Peschanski, Marc; Martinat, Cécile; Baghdoyan, Sandrine

doi:10.3390/cells8121523

Cited by 4 publications

(2 citation statements)

References 68 publications

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“…Others have also suggested that the MAPK and SHH pathways modulate DIO3 expression in papillary thyroid carcinomas and in an MTC cell line [ 32 ]. Recently, it was demonstrated that the osteogenic fate of human pluripotent stem cell lines is associated with the methylation status and the expression of miRNAs from the imprinted DLK1/DIO3 locus [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Assessment of Copy Number Alterations Uncovers Recurrent AIFM3 and DLK1 Copy Gain in Medullary Thyroid Carcinoma

Araújo

Camacho

Mendes

et al. 2021

Cancers

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Medullary thyroid carcinoma (MTC) is a malignant tumor originating from thyroid C-cells that can occur either in sporadic (70–80%) or hereditary (20–30%) form. In this study we aimed to identify recurrent copy number alterations (CNA) that might be related to the pathogenesis or progression of MTC. We used Affymetrix SNP array 6.0 on MTC and paired-blood samples to identify CNA using PennCNV and Genotyping Console software. The algorithms identified recurrent copy number gains in chromosomes 15q, 10q, 14q and 22q in MTC, whereas 4q cumulated losses. Coding genes were identified within CNA regions. The quantitative PCR analysis performed in an independent series of MTCs (n = 51) confirmed focal recurrent copy number gains encompassing the DLK1 (14q32.2) and AIFM3 (22q11.21) genes. Immunohistochemistry confirmed AIFM3 and DLK1 expression in MTC cases, while no expression was found in normal thyroid tissues and few MTC samples were found with normal copy numbers. The functional relevance of CNA was also assessed by in silico analysis. CNA status correlated with protein expression (DLK1, p = 0.01), tumor size (DLK1, p = 0.04) and AJCC staging (AIFM3p = 0.01 and DLK1p = 0.05). These data provide a novel insight into MTC biology, and suggest a common CNA landscape, regardless of if it is sporadic or hereditary MTC.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Assessment of Copy Number Alterations Uncovers Recurrent AIFM3 and DLK1 Copy Gain in Medullary Thyroid Carcinoma

Araújo

Camacho

Mendes

et al. 2021

Cancers

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“…hiPSCs were derived by Phenocell® from human primary fibroblasts reprogrammed using sendai virus vectors carrying OCT4, KLF4, SOX2 and c-Myc ( 56 ). Two DM1 hiPSC lines were generated from two independent patients’ fibroblasts containing ~2500 CTG repeats.…”

Section: Methodsmentioning

confidence: 99%

CRISPR gene editing in pluripotent stem cells reveals the function of MBNL proteins during humanin vitromyogenesis

Mérien

Tahraoui-Bories

Cailleret

et al. 2021

Human Molecular Genetics

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Alternative splicing has emerged as a fundamental mechanism for the spatiotemporal control of development. A better understanding of how this mechanism is regulated has the potential not only to elucidate fundamental biological principles, but also to decipher pathological mechanisms implicated in diseases where normal splicing networks are mis-regulated. Here, we took advantage of human pluripotent stem cells to decipher during human myogenesis the role of MBNL proteins, a family of tissue-specific splicing regulators whose loss of function is associated with Myotonic Dystrophy type 1 (DM1), an inherited neuromuscular disease. Thanks to the CRISPR/Cas9 technology, we generated human-induced pluripotent stem cells (hiPSCs) depleted in MBNL proteins and evaluated the consequences of their losses on the generation of skeletal muscle cells. Our results suggested that MBNL proteins are required for the late myogenic maturation. In addition, loss of MBNL1 and MBNL2 recapitulated the main features of DM1 observed in hiPSC-derived skeletal muscle cells. Comparative transcriptomic analyses also revealed the muscle-related processes regulated by these proteins that are commonly mis-regulated in DM1. Together, our study reveals the temporal requirement of MBNL proteins in human myogenesis and should facilitate the identification of new therapeutic strategies capable to cope with the loss of function of these MBNL proteins.

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Interaction of PGC7 and HP1BP3 Maintains Meg3‐DMR Methylation by Regulating Chromatin Configuration

Liu,

Hao,

Huang

et al. 2024

J of Cellular Biochemistry

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Genomic imprinting is essential for mammalian development. PGC7, an important maternal factor, binds to dimethylated histone H3K9 (H3K9me2), maintaining DNA methylation in zygotes and stem cells. However, the underlying molecular mechanisms of PGC7‐maintained genomic imprinting in stem cells are not clear. Our previous study has identified that PGC7 interacts with HP1BP3, a novel member of the histone H1 family. In this study, we found that PGC7 interacts with the central globular domain of HP1BP3 through its C‐terminal tail and that HP1BP3 is responsible for the recruitment of PGC7 at the Meg3 differentially methylated region (DMR) in the Dlk1–Dio3 imprinted domain. HP1BP3 or PGC7 depletion decreases enrichment in the Meg3‐DMR, leading to DNA hypermethylation in this region. Moreover, the cooperative binding of PGC7 and HP1BP3 can antagonize the enrichment of DNMT3A in the Meg3‐DMR, and the depletion of HP1BP3 or PGC7 separately induces chromosome decondensation in this region. In summary, this is the first study demonstrating that PGC7 and HP1BP3 synergistically maintain the methylation status of the Meg3‐DMR by enabling a chromatin configuration that interferes with the binding of the de novo DNA methyltransferase DNMT3A.

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Expression of miRNAs from the Imprinted DLK1/DIO3 Locus Signals the Osteogenic Potential of Human Pluripotent Stem Cells

Cited by 4 publications

References 68 publications

Comprehensive Assessment of Copy Number Alterations Uncovers Recurrent AIFM3 and DLK1 Copy Gain in Medullary Thyroid Carcinoma

Comprehensive Assessment of Copy Number Alterations Uncovers Recurrent AIFM3 and DLK1 Copy Gain in Medullary Thyroid Carcinoma

CRISPR gene editing in pluripotent stem cells reveals the function of MBNL proteins during humanin vitromyogenesis

Interaction of PGC7 and HP1BP3 Maintains Meg3‐DMR Methylation by Regulating Chromatin Configuration

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