Vitamin D receptor–retinoid X receptor heterodimer signaling regulates oligodendrocyte progenitor cell differentiation

Fuente, Alerie Guzman de la; Errea, Oihana; Wijngaarden, Peter van; González, Ginez A.; Kerninon, Christophe; Jarjour, Andrew A.; Lewis, Hilary; Jones, Clare A.; Nait‐Oumesmar, Brahim; Zhao, Chao; Huang, Jeffrey K.; ffrench‐Constant, Charles; Franklin, Robin J.M.

doi:10.1083/jcb.201505119

Cited by 120 publications

(61 citation statements)

References 61 publications

(41 reference statements)

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“…In general, NFATC2 is believed to induce transcription, but multiple reports indicate a function as transcriptional repressor as well (Ranger et al 2000;Baksh et al 2002;Carvalho et al 2007;Baumgart et al 2012). And finally, RXRG is a member of the ligand-responsive transcription factor family of retinoic acid/X receptors and is able to activate a variety of cellular processes, depending on its partner nuclear receptor in the DNA-binding heterodimer complex (Altucci et al 2007; de la Fuente et al 2015). It promotes the dedifferentiation and invasion of tumor cells Papi et al 2010) and has been shown to be involved in minimal residual disease of melanoma (Rambow et al 2018).…”

Section: Discussionmentioning

confidence: 99%

Single-cell gene regulatory network analysis reveals new melanoma cell states and transition trajectories during phenotype switching

Wouters

Atak

Minnoye

et al. 2019

Preprint

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Melanoma is notorious for its cellular heterogeneity, which is at least partly due to its ability to transition between alternate cell states. Similarly to EMT, melanoma cells with a melanocytic phenotype can switch to a mesenchymal-like phenotype. However, scattered emerging evidence indicates that additional, intermediate state(s) may exist. In order to search for such new melanoma states and decipher their underlying gene regulatory network (GRN), we extensively studied ten patient-derived melanoma cultures by single-cell RNA-seq of >39,000 cells. Although each culture exhibited a unique transcriptome, we identified shared gene regulatory networks that underlie the extreme melanocytic and mesenchymal cell states, as well as one (stable) intermediate state. The intermediate state was corroborated by a distinct open chromatin landscape and governed by the transcription factors EGR3, NFATC2, and RXRG. Single-cell migration assays established that this "transition" state exhibits an intermediate migratory phenotype. Through a dense time-series sampling of single cells and dynamic GRN inference, we unraveled the sequential and recurrent arrangement of transcriptional programs at play during phenotype switching that ultimately lead to the mesenchymal cell state. We provide the scRNA-Seq data with 39,263 melanoma cells on our SCope platform and the ATAC-seq data on a UCSC hub to jointly serve as a resource for the melanoma field. Together, this exhaustive analysis of melanoma cell state diversity indicates that additional states exists between the two extreme melanocytic and mesenchymal-like states. The GRN we identified may serve as a new putative target to prevent the switch to mesenchymal cell state and thereby, acquisition of metastatic and drug resistant potential.

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Section: Discussionmentioning

confidence: 99%

Single-cell gene regulatory network analysis reveals new melanoma cell states and transition trajectories during phenotype switching

Wouters

Atak

Minnoye

et al. 2019

Preprint

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“…OPCs were isolated by shaking off loosely adherent cells from the astrocyte adherent cell monolayer. The supernatant (enriched in OPCs) was collected and microglial cells were removed by incubation in plastic Corning petri dishes (BD, Oxford, UK) 15 min at 37 C. As previously described, this procedure results in a relatively pure population of OPCs (de la Fuente et al, 2015). Indeed, we determined that 92 ± 4% of total cells were Olig2-expressing undifferentiated OPCs.…”

Section: Opcs Culturesmentioning

confidence: 99%

Aging restricts the ability of mesenchymal stem cells to promote the generation of oligodendrocytes during remyelination

Rivera

Fuente

Zhao

et al. 2019

Glia

Self Cite

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Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that leads to severe neurological deficits. Due to their immunomodulatory and neuroprotective activities and their ability to promote the generation of oligodendrocytes, mesenchymal stem cells (MSCs) are currently being developed for autologous cell therapy in MS. As aging reduces the regenerative capacity of all tissues, it is of relevance to investigate whether MSCs retain their pro‐oligodendrogenic activity with increasing age. We demonstrate that MSCs derived from aged rats have a reduced capacity to induce oligodendrocyte differentiation of adult CNS stem/progenitor cells. Aging also abolished the ability of MSCs to enhance the generation of myelin‐like sheaths in demyelinated cerebellar slice cultures. Finally, in a rat model for CNS demyelination, aging suppressed the capability of systemically transplanted MSCs to boost oligodendrocyte progenitor cell (OPC) differentiation during remyelination. Thus, aging restricts the ability of MSCs to support the generation of oligodendrocytes and consequently inhibits their capacity to enhance the generation of myelin‐like sheaths. These findings may impact on the design of therapies using autologous MSCs in older MS patients.

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“…Interestingly, two of the aforementioned transcriptional hubs, RXRA-NR1H3 complex and SREBF1, have been previously described as master regulators of lipid synthesis in mammary epithelial cells6162, corroborating our results. Among the remaining hubs, MXI1, NFE2, RXRA-VDR and RAD21 have known role in cell differentiation63646566. To the best of our knowledge, RFX5 does not have any previously known association with BC cell differentiation.…”

Section: Resultsmentioning

confidence: 81%

BGRMI: A method for inferring gene regulatory networks from time-course gene expression data and its application in breast cancer research

Iglesias-Martinez

Kölch

Santra

2016

Sci Rep

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Reconstructing gene regulatory networks (GRNs) from gene expression data is a challenging problem. Existing GRN reconstruction algorithms can be broadly divided into model-free and model–based methods. Typically, model-free methods have high accuracy but are computation intensive whereas model-based methods are fast but less accurate. We propose Bayesian Gene Regulation Model Inference (BGRMI), a model-based method for inferring GRNs from time-course gene expression data. BGRMI uses a Bayesian framework to calculate the probability of different models of GRNs and a heuristic search strategy to scan the model space efficiently. Using benchmark datasets, we show that BGRMI has higher/comparable accuracy at a fraction of the computational cost of competing algorithms. Additionally, it can incorporate prior knowledge of potential gene regulation mechanisms and TF hetero-dimerization processes in the GRN reconstruction process. We incorporated existing ChIP-seq data and known protein interactions between TFs in BGRMI as sources of prior knowledge to reconstruct transcription regulatory networks of proliferating and differentiating breast cancer (BC) cells from time-course gene expression data. The reconstructed networks revealed key driver genes of proliferation and differentiation in BC cells. Some of these genes were not previously studied in the context of BC, but may have clinical relevance in BC treatment.

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Vitamin D receptor–retinoid X receptor heterodimer signaling regulates oligodendrocyte progenitor cell differentiation

Abstract: Activation of retinoid X receptor γ and vitamin D receptor (VDR) heterodimer via vitamin D enhances oligodendrocyte progenitor differentiation, whereas blocking VDR impairs differentiation and myelination ex vivo.

Cited by 120 publications

References 61 publications

Single-cell gene regulatory network analysis reveals new melanoma cell states and transition trajectories during phenotype switching

Single-cell gene regulatory network analysis reveals new melanoma cell states and transition trajectories during phenotype switching

Aging restricts the ability of mesenchymal stem cells to promote the generation of oligodendrocytes during remyelination

BGRMI: A method for inferring gene regulatory networks from time-course gene expression data and its application in breast cancer research

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