Transduction of Oct6 or Oct9 gene concomitant with Myc family gene induced osteoblast-like phenotypic conversion in normal human fibroblasts

Mizoshiri, Naoki; Kishida, Tsunao; Yamamoto, Kenta; Shirai, Toshiharu; Terauchi, Ryu; Tsuchida, Shinji; Mori, Yuki; Ejima, Akika; Satô, Yoshiki; Fujiwara, Hiroyoshi; Yamamoto, Toshiro; Kanamura, Narisato; Mazda, Osam; Kubo, Toshikazu

doi:10.1016/j.bbrc.2015.10.098

Cited by 16 publications

(18 citation statements)

References 35 publications

(37 reference statements)

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“…Mycn is known to play an essential role in the maintenance of pluripotency ( 38 ). Mycn can cooperate with other TFs to reprogram adult cells into other differentiated cells ( 39 ) or into iPS cells ( 40 ). Msx2, another transcription factor identified in our enrichment analysis, is a major driver of de-differentiation in mammalian muscle cells ( 41 ).…”

Section: Resultsmentioning

confidence: 99%

SEASTAR: systematic evaluation of alternative transcription start sites in RNA

Qin

Stoilov

Zhang

et al. 2018

Nucleic Acids Research

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Alternative first exons diversify the transcriptomes of eukaryotes by producing variants of the 5′ Untranslated Regions (5′UTRs) and N-terminal coding sequences. Accurate transcriptome-wide detection of alternative first exons typically requires specialized experimental approaches that are designed to identify the 5′ ends of transcripts. We developed a computational pipeline SEASTAR that identifies first exons from RNA-seq data alone then quantifies and compares alternative first exon usage across multiple biological conditions. The exons inferred by SEASTAR coincide with transcription start sites identified directly by CAGE experiments and bear epigenetic hallmarks of active promoters. To determine if differential usage of alternative first exons can yield insights into the mechanism controlling gene expression, we applied SEASTAR to an RNA-seq dataset that tracked the reprogramming of mouse fibroblasts into induced pluripotent stem cells. We observed dynamic temporal changes in the usage of alternative first exons, along with correlated changes in transcription factor expression. Using a combined sequence motif and gene set enrichment analysis we identified N-Myc as a regulator of alternative first exon usage in the pluripotent state. Our results demonstrate that SEASTAR can leverage the available RNA-seq data to gain insights into the control of gene expression and alternative transcript variation in eukaryotic transcriptomes.

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Section: Resultsmentioning

confidence: 99%

SEASTAR: systematic evaluation of alternative transcription start sites in RNA

Qin

Stoilov

Zhang

et al. 2018

Nucleic Acids Research

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“…Genetic approaches have successfully converted dermal fibroblasts into osteoblasts in several studies . For example, overexpression of the muscle master transcription factor MyoD in myoblasts can increase their sensitivity to bone morphogenetic protein (BMP‐2), thus enhancing BMP signaling to drive trans‐differentiation into OB.…”

Section: Discussionmentioning

confidence: 99%

“…Genetic approaches have successfully converted dermal fibroblasts into osteoblasts in several studies. [36][37][38][39] For example, overexpression of the muscle master transcription factor MyoD in F I G U R E 7 IGFBP7-induced osteoblastic reprogramming is dependent on Il-6. Fibroblasts were treated with IGFBP7 (1000 ng/mL) together with IgG control antibody (50 μg/mL) or IL-6 neutralizing antibody (5 μg/mL).…”

Section: Discussionmentioning

confidence: 99%

Reprogramming of human fibroblasts into osteoblasts by insulin-like growth factor-binding protein 7

Chiu

Lee

et al. 2020

Stem Cells Translational Medicine

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The induced pluripotent stem cell (iPSC) is a promising cell source for tissue regeneration. However, the therapeutic value of iPSC technology is limited due to the complexity of induction protocols and potential risks of teratoma formation. A trans‐differentiation approach employing natural factors may allow better control over reprogramming and improved safety. We report here a novel approach to drive trans‐differentiation of human fibroblasts into functional osteoblasts using insulin‐like growth factor binding protein 7 (IGFBP7). We initially determined that media conditioned by human osteoblasts can induce reprogramming of human fibroblasts to functional osteoblasts. Proteomic analysis identified IGFBP7 as being significantly elevated in media conditioned with osteoblasts compared with those with fibroblasts. Recombinant IGFBP7 induced a phenotypic switch from fibroblasts to osteoblasts. The switch was associated with senescence and dependent on autocrine IL‐6 signaling. Our study supports a novel strategy for regenerating bone by using IGFBP7 to trans‐differentiate fibroblasts to osteoblasts.

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“…In addition, iOBs did not require continuous expression of the exogenous genes to maintain their phenotypes. Mizoshiri et al reported that L-myc in combination with either Oct3/4, Oct6, or Oct9 enabled the conversion of fibroblasts to osteoblasts [ 96 ]. Alternatively, Oct9 plus N-myc had the strongest capability of inducing osteoblastic phenotype.…”

Section: Direct Reprogrammingmentioning

confidence: 99%

Cellular Reprogramming Using Defined Factors and MicroRNAs

Eguchi

Kuboki

2016

Stem Cells International

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Development of human bodies, organs, and tissues contains numerous steps of cellular differentiation including an initial zygote, embryonic stem (ES) cells, three germ layers, and multiple expertized lineages of cells. Induced pluripotent stem (iPS) cells have been recently developed using defined reprogramming factors such as Nanog, Klf5, Oct3/4 (Pou5f1), Sox2, and Myc. This outstanding innovation is largely changing life science and medicine. Methods of direct reprogramming of cells into myocytes, neurons, chondrocytes, and osteoblasts have been further developed using modified combination of factors such as N-myc, L-myc, Sox9, and microRNAs in defined cell/tissue culture conditions. Mesenchymal stem cells (MSCs) and dental pulp stem cells (DPSCs) are also emerging multipotent stem cells with particular microRNA expression signatures. It was shown that miRNA-720 had a role in cellular reprogramming through targeting the pluripotency factor Nanog and induction of DNA methyltransferases (DNMTs). This review reports histories, topics, and idea of cellular reprogramming.

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Transduction of Oct6 or Oct9 gene concomitant with Myc family gene induced osteoblast-like phenotypic conversion in normal human fibroblasts

Abstract: The present findings may greatly contribute to the elucidation of the roles of the Oct and Myc proteins in osteoblast direct reprogramming. The results may also lead to establishment of novel regenerative therapy for various bone resorption diseases.

Cited by 16 publications

References 35 publications

SEASTAR: systematic evaluation of alternative transcription start sites in RNA

SEASTAR: systematic evaluation of alternative transcription start sites in RNA

Reprogramming of human fibroblasts into osteoblasts by insulin-like growth factor-binding protein 7

Cellular Reprogramming Using Defined Factors and MicroRNAs

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