MIcrophthalmia-associated Transcription Factor (MITF) regulates melanocyte and melanoma physiology. ShRNA-mediated silencing of the NURF subunit BPTF revealed its essential role in several melanoma cell lines and in untransformed melanocytes in vitro. Comparative RNA-seq shows that MITF and BPTF co-regulate overlapping gene expression programs in cell lines in vitro. Somatic and specific inactivation of Bptf in developing murine melanoblasts in vivo shows that Bptf regulates their proliferation, migration and morphology. Once born, Bptf-mutant mice display premature greying where the second post-natal coat is white. This second coat is normally pigmented by differentiated melanocytes derived from the adult melanocyte stem cell (MSC) population that is stimulated to proliferate and differentiate at anagen. An MSC population is established and maintained throughout the life of the Bptf- mutant mice, but these MSCs are abnormal and at anagen, give rise to reduced numbers of transient amplifying cells (TACs) that do not express melanocyte markers and fail to differentiate into mature melanin producing melanocytes. MSCs display a transcriptionally repressed chromatin state and Bptf is essential for reactivation of the melanocyte gene expression program at anagen, the subsequent normal proliferation of TACs and their differentiation into mature melanocytes. Overall design: 5 samples corresponding to mRNA profiles of 501Mel and Hermes3A after BPTF shRNA-mediated knockdown were generated by deep sequencing in triplicate (Hermes 3A) or duplicate (501Mel), using HiSeq2500.
Chromatin-Remodelling Complex NURF Is Essential for Differentiation of Adult Melanocyte Stem Cells.
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Cell growth in aggregates determines gene expression, proliferation, survival, chemoresistance, and sensitivity to immune effectors in follicular lymphoma.
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View SamplesFollicular Lymphomas are blood tumors growing as spheres in patients. Before this study, there was no experimental model mimicking the 3D organization of these in vivo tumors. We develop such a model, called MALC, and observed a progressive enrichment in quiescent cells in these with time of culture; these cells were sorted, as their cycling counterparts, and their transcriptomes were compared. We used microarrays to detail the differential global gene expression profile between quiescent and cycling cells isolated from MALC.
Cell growth in aggregates determines gene expression, proliferation, survival, chemoresistance, and sensitivity to immune effectors in follicular lymphoma.
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View SamplesFollicular Lymphomas are blood tumors growing as spheres in patients. Before this study, there was no experimental model mimicking the 3D organization of these in vivo tumors. We develop such a model, called MALC, and performed a pan-genomic comparative analysis between MALC and classical suspension cultures. We used microarrays to detail the global gene expression profile induced by aggregated growth of lymphoma cells.
Cell growth in aggregates determines gene expression, proliferation, survival, chemoresistance, and sensitivity to immune effectors in follicular lymphoma.
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View SamplesMicrophthalmia-associated transcription factor (MITF) is the master regulator of the melanocyte lineage. By tandem affinity purification and mass spectrometry, we present a comprehensive characterisation of the MITF interactome comprising multiple novel cofactors involved in transcription, DNA replication and repair and chromatin organisation, including a BRG1 chromatin remodelling complex comprising CHD7. BRG1 is essential for melanoma cell proliferation in vitro and for normal melanocyte development in vivo. MITF and SOX10 actively recruit BRG1 to a set of MITF-associated regulatory elements (MAREs) at active enhancers. MITF, SOX10 and YY1 bind between two BRG1-occupied nucleosomes thus defining both a combinatorial signature of transcription factors essential for the melanocyte lineage and a specific chromatin organisation of MAREs. Nevertheless, BRG1 silencing enhances MITF occupancy at MAREs showing that BRG1 acts to promote dynamic MITF interactions with chromatin. Overall design: 19 samples corresponding to mRNA profiles of 501Mel and Hermes3A after MITF, BRG1 or control shRNA-mediated knockdown were generated by deep sequencing in triplicate (in duplicate for 501_shMITF and corresponding control 501_shSCR2), using HiSeq2500.
Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells.
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View SamplesExhaustion markers are expressed by T lymphocytes in Follicular Lymphoma (FL). Through these, TIM-3 has been recently identified as a poor pronostic factor when expressed by FL CD4+ T cells.
Impaired functional responses in follicular lymphoma CD8<sup>+</sup>TIM-3<sup>+</sup> T lymphocytes following TCR engagement.
Specimen part, Subject
View SamplesRetinoic acid receptors (RARs) , and are key regulators of embryonic development. Hematopoietic differentiation is regulated by RAR, and several types of leukemia show aberrant RAR activity. We demonstrate that RAR plays an important role in cellular memory and imprinting by regulating the CpG methylation status of specific promoter regions.
Epigenetic regulation by RARα maintains ligand-independent transcriptional activity.
Cell line, Treatment
View SamplesThe t(12;21) translocation is the most common genetic rearrangement in childhood acute lymphoblastic leukemia (ALL) and gives rise to the TEL-AML1 fusion gene, which functions as a transcription factor.
The TEL-AML1 fusion protein of acute lymphoblastic leukemia modulates IRF3 activity during early B-cell differentiation.
Cell line, Treatment
View SamplesIntegrins have long been known to have a role in adhesion of neural stem cells within the neuroepithelium, but little is known about their role in regulating stem cell behaviour through signalling. We aimed to investigate the effect of integrin-beta 1 signalling (itgb1) on these cells by transfection of a constitutively active itgb1. This creates a heterogenous pattern of expression allowing the study of cell-autonomous and non-cell autonomous effects.
Integrin signalling regulates the expansion of neuroepithelial progenitors and neurogenesis via Wnt7a and Decorin.
Specimen part
View SamplesRetinoic acid receptors (RARs) , , and heterodimerize with Retinoid X receptors (RXR) , , and and bind the cis-acting response elements known as RAREs to execute the biological functions of retinoic acid during mammalian development. RAR mediates the anti-proliferative and apoptotic effects of retinoids in certain tissues and cancer cells, such as melanoma and neuroblastoma cells. Furthermore, ablation of RAR enhanced the tumor incidence of Ras transformed keratinocytes and was associated with resistance to retinoid mediated growth arrest and apoptosis.
RARγ is essential for retinoic acid induced chromatin remodeling and transcriptional activation in embryonic stem cells.
Specimen part, Treatment, Time
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