Foxd1 is a mediator and indicator of the cell reprogramming process

Koga, Makito; Matsuda, Mitsuhiro; Kawamura, Teruhisa; Sogo, Takahiro; Shigeno, Asako; Nishida, Eisuke; Ebisuya, Miki

doi:10.1038/ncomms4197

Cited by 68 publications

(62 citation statements)

References 45 publications

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“…SIRT1 can induce deacetylation of FOXO1, one pluripotent regulator that directly regulates gene expression in either human or mouse ESCs (Zhang et al ., 2011). Another study showed that knockdown of FOXO1 reduced the reprogramming efficiency as well (Koga et al ., 2014). Additionally, the age‐dependent decline in reprogramming efficiency could be reversed by silencing p53 expression (Kawamura et al ., 2009).…”

Section: Discussionmentioning

confidence: 99%

Blockade of senescence‐associated micro RNA ‐195 in aged skeletal muscle cells facilitates reprogramming to produce induced pluripotent stem cells.

et al. 2015

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SummaryThe low reprogramming efficiency in cells from elderly patients is a challenge that must be overcome. Recently, it has been reported that senescence‐associated microRNA (miR)‐195 targets Sirtuin 1 (SIRT1) to advance cellular senescence. Thus, we hypothesized that a blockade of miR‐195 expression could improve reprogramming efficiency in old skeletal myoblasts (SkMs). We found that miR‐195 expression was significantly higher in old SkMs (24 months) isolated from C57BL/6 mice as compared to young SkMs (2 months, 2.3‐fold). Expression of SIRT1 and telomerase reverse transcriptase (TERT) was downregulated in old SkMs, and transduction of old SkMs with lentiviral miR‐195 inhibitor significantly restored their expression. Furthermore, quantitative in situ hybridization analysis demonstrated significant telomere elongation in old SkMs transduced with anti‐miR‐195 (1.7‐fold increase). It is important to note that blocking miR‐195 expression markedly increased the reprogramming efficiency of old SkMs as compared to scramble (2.2‐fold increase). Transduction of anti‐miR‐195 did not alter karyotype or pluripotency marker expression. Induced pluripotent stem cells (iPSCs) from old SkMs transduced with anti‐miR‐195 successfully formed embryoid bodies that spontaneously differentiated into three germ layers, indicating that deletion of miR‐195 does not affect pluripotency in transformed SkMs. In conclusion, this study provided novel evidence that the blockade of age‐induced miR‐195 is a promising approach for efficient iPSC generation from aging donor subjects, which has the potential for autologous transplantation of iPSCs in elderly patients.

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Section: Discussionmentioning

confidence: 99%

Blockade of senescence‐associated micro RNA ‐195 in aged skeletal muscle cells facilitates reprogramming to produce induced pluripotent stem cells.

et al. 2015

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“…Brn2 is therefore an upstream regulator of a network specifying neuronal identity of differentiating ESCs. In the absence of Brn2, surviving cells showed a loss of the axonal network, reduced expression of many neurogenic genes and, instead, expressed a diverse set of genes associated with mesoderm and endoderm differentiation and showed upregulated expression of Foxd1, a marker for reprogramming of cell fate (Koga et al, 2014). These cells also show a more general defect characterised by the activation of the interferon response.…”

Section: Brn2 Is Essential For the Neuronal Identity Of Retinoic-acidmentioning

confidence: 97%

A Brn2–Zic1 axis specifies the neuronal fate of retinoic-acid-treated embryonic stem cells

Urban

Kobi

Ennen

et al. 2015

Journal of Cell Science

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Mouse embryonic stem cells (ESCs) treated with all-trans retinoic acid differentiate into a homogenous population of glutamatergic neurons. Although differentiation is initiated through activation of target genes by the retinoic acid receptors, the downstream transcription factors specifying neuronal fate are less well characterised. Here, we show that the transcription factor Brn2 (also known as Pou3f2) is essential for the neuronal differentiation programme. By integrating results from RNA-seq following Brn2 silencing with results from Brn2 ChIP-seq, we identify a set of Brn2 target genes required for the neurogenic programme. Further integration of Brn2 ChIP-seq data from retinoicacid-treated ESCs and P19 cells with data from ESCs differentiated into neuronal precursors by Fgf2 treatment and that from fibroblasts trans-differentiated into neurons by ectopic Brn2 expression showed that Brn2 occupied a distinct but overlapping set of genomic loci in these differing conditions. However, a set of common binding sites and target genes defined the core of the Brn2-regulated neuronal programme, among which was that encoding the transcription factor Zic1. Small hairpin RNA (shRNA)-mediated silencing of Zic1 prevented ESCs from differentiating into neuronal precursors, thus defining a hierarchical Brn2-Zic1 axis that is essential to specify neural fate in retinoic-acid-treated ESCs.

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“…Furthermore, FOXD1 was found to be a mediator and indicator of cell reprogramming by mediating self-renewal and differentiation [6,7]. Increasing evidence has indicated that cell reprogramming is associated with tumor initiation and progress [8].…”

Section: Introductionmentioning

confidence: 99%

FOXD1 Promotes Cell Growth and Metastasis by Activation of Vimentin in NSCLC

Fan

et al. 2018

Cell Physiol Biochem

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Background/Aims: Forkhead box D1 (FOXD1) has a well-established role in early embryonic development and organogenesis and functions as an oncogene in several cancers. However, the clinical significance and biological roles of FOXD1 in non-small cell lung cancer (NSCLC) remain largely unknown. Methods: A total of 264 primary NSCLC tissue samples were collected. The expression levels of FOXD1 in these samples were examined by immunohistochemical staining. The expression of FOXD1 was knocked down by lentiviral shRNA. The relative expression of FOXD1 was determined by qRT-PCR, Western blotting and immunofluorescence image. The functional roles of FOXD1 in NSCLC were demonstrated cell viability CCK-8 assay, colony formation, cell invasion and migration assays, and cell apoptosis assay in vitro. In vivo mouse xenograft and metastasis models were used to assess tumorigenicity and metastatic ability. The Chi-square test was used to assess the correlation between FOXD1 expression and the clinicopathological characteristics. Survival curves were estimated by Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was used for univariate and multivariate analyses. Results: We determined that higher levels of FOXD1 were present in NSCLC tissues, especially in metastatic NSCLC tissues. FOXD1 was also higher in all NSCLC cells compared with normal human bronchial epithelial cells. A higher expression level of FOXD1 was associated with malignant behavior and poor prognosis in NSCLC patients. Knockdown of FOXD1 significantly inhibited proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo, and it increased the apoptosis rates of NSCLC cells. Mechanistic analyses revealed that FOXD1 expressed its oncogenic characteristics through activating Vimentin in NSCLC. Multivariate Cox regression analysis indicated that FOXD1 was an independent prognostic factor both for overall survival (OS) and disease-free survival (DFS) in NSCLC patients. Conclusion: Our results indicated that FOXD1 might be involved in the development and progression of NSCLC as an oncogene, and thereby might be a potential therapeutic target for NSCLC patients.

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Foxd1 is a mediator and indicator of the cell reprogramming process

Cited by 68 publications

References 45 publications

Blockade of senescence‐associated micro RNA ‐195 in aged skeletal muscle cells facilitates reprogramming to produce induced pluripotent stem cells.

Blockade of senescence‐associated micro RNA ‐195 in aged skeletal muscle cells facilitates reprogramming to produce induced pluripotent stem cells.

A Brn2–Zic1 axis specifies the neuronal fate of retinoic-acid-treated embryonic stem cells

FOXD1 Promotes Cell Growth and Metastasis by Activation of Vimentin in NSCLC

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