Jakub Mieczkowski

Jakub Mieczkowski
Nencki Institute of Experimental Biology | NENCKI · Neurobiology Center

PhD

About

81
Publications
7,733
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1,044
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Additional affiliations
October 2008 - March 2013
Nencki Institute of Experimental Biology
Position
  • PhD Student

Publications

Publications (81)
Preprint
Local hypoxia (low oxygen) occurs in most solid tumors and is associated with aggressive disease and therapy resistance. Widespread changes in gene expression play a critical role in the biological response to hypoxia. However, most of the prior research has focused on hypoxia-inducible genes in hypoxia as opposed to those which are decreased. Usin...
Preprint
Full-text available
Visium Spatial Gene Expression (ST) is a method combining histological spatial information with transcriptomics profiles directly from tissue sections. The use of spatial information has made it possible to discover novel modes of gene expression regulations. However, in the ST experiment, the nucleus size of cells may exceed the thickness of a tis...
Article
Full-text available
Chronic and acute myeloid leukemia (CML, AML) evade immune system surveillance and induce immunosuppression by expanding pro-leukemic Foxp3+ regulatory T cells (Tregs). High levels of immunosuppressive Tregs predict inferior response to chemotherapy, leukemia relapse and shorter survival. However, mechanisms that promote Tregs in myeloid leukemias...
Preprint
Visium Spatial Gene Expression (ST) is a method combining histological spatial information with transcriptomics profiles directly from tissue sections. The use of spatial information has made it possible to discover new modes of gene expression regulations. However, in the ST experiment, the nucleus size of cells may exceed the thickness of a tissu...
Article
Full-text available
Somatic mutations in histone encoding genes result in gross alterations in the epigenetic landscape. Diffuse intrinsic pontine glioma (DIPG) is a pediatric high-grade glioma (pHGG) and one of the most challenging cancers to treat, with only 1% surviving for 5 years. Due to location in the brainstem, DIPGs are difficult to resect and rapidly turn in...
Article
BACKGROUND Chromatin structure is often dysregulated in cancers, including glioblastoma (GBM), the most aggressive type of primary brain tumor. GBM has the poorest prognosis with no efficient cure to date due to diffusive growth into the brain, resistance to treatments and the immunosuppressive tumor microenvironment (TME). The growth and invasiven...
Article
Full-text available
Chromatin structure is often dysregulated in cancers, including glioblastoma (GBM), the most common primary brain tumor in adults. GBM has the poorest prognosis and no efficient cure to date due to diffusive growth into the surrounding brain, preventing complete surgical resection and leading to inevitable tumor relapse. Tumor microenvironment (TME...
Article
Full-text available
Malignant gliomas represent over 70% of primary brain tumors and the most deadly is glioblastoma (GBM, WHO grade IV), due to frequent dysfunctions of tumor suppressors or/and oncogenes. Recent whole genome studies of gliomas demonstrated that besides genetic alterations, epigenetic dysfunctions contribute to tumor development and progression. Alter...
Article
Full-text available
Chromatin structure and accessibility, and combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations in genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics and result in alterations in gene expression contributing to cancer develop...
Article
Full-text available
Microglia are resident myeloid cells in the central nervous system (CNS) that control homeostasis and protect CNS from damage and infections. Microglia and peripheral myeloid cells accumulate and adapt tumor supporting roles in human glioblastomas that show prevalence in men. Cell heterogeneity and functional phenotypes of myeloid subpopulations in...
Article
Full-text available
Accumulating evidence suggests that glioma stem cells (GSCs), which are rare cells characterized by pluripotency and self-renewal ability, are responsible for glioblastoma (GBM) propagation, recurrence and resistance to therapies. Bone morphogenic proteins (BMPs) induce GSC differentiation, which leads to elimination of GSCs and sensitization of gl...
Article
Full-text available
Remyelination, a highly efficient central nervous system (CNS) regenerative process, is performed by oligodendrocyte progenitor cells (OPCs), which are recruited to the demyelination sites and differentiate into mature oligodendrocytes to form a new myelin sheath. Microglia, the specialized CNS-resident phagocytes, were shown to support remyelinati...
Preprint
Full-text available
Chromatin structure and accessibility, and combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations in genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics and result in alterations in gene expression contributing to cancer develop...
Conference Paper
Glioblastoma (GBM) is the most aggressive primary brain tumor showing the poorest prognosis. Despite extensive research, no significant improvement in glioma therapy. GBM microenvironment has been shown to contribute to the aggressiveness of the tumor and influences overall survival. Tumor associated microglia and macrophages (TAMs) contribute to t...
Preprint
Full-text available
Brain resident and infiltrating innate immune cells adapt a tumor-supportive phenotype in the glioma microenvironment. Flow cytometry analysis supported by a single-cell RNA sequencing study of human gliomas indicate considerable cell type heterogeneity. It remains disputable whether microglia and infiltrating macrophages have the same or distinct...
Article
Transcription factor signal transducer and activator of transcription 3 (STAT3) is constitutively activated in many cancers and promotes uncontrolled tumor growth and progression through multiple mechanisms. Compelling evidence shows tissue and cell-specific sets of STAT3 targets. Transcriptional targets of STAT3 in melanoma cells are largely unkno...
Article
Background Glioma is the most common primary brain tumour and often confers a grave prognosis. In low-grade gliomas seizures occur frequently (70–80%) and usually are pharmacoresistant. While genes coding for interleukins and implicated in neurotransmitters signalling have been associated with focal seizures, a molecular profile of glioma-associate...
Article
Full-text available
Following CNS demyelination, oligodendrocyte progenitor cells (OPCs) are able to differentiate into either remyelinating oligodendrocytes (OLs) or remyelinating Schwann cells (SCs). However, the signals that determine which type of remyelinating cell is generated and the underlying mechanisms involved have not been identified. Here, we show that di...
Data
Genes significantly regulated in the vascular niche. Dots represent level of expression for individual animal sample.
Data
Genes significantly regulated in the non-vascular areas. Dots represent level of expression for individual animal sample.
Data
Genes significantly regulated only in the vascular niche. Dots represent level of expression for individual animal sample.
Chapter
Assays profiling nucleosome positioning and occupancy are often coupled with high-throughput sequencing, which results in generation of large data sets. These data sets require processing in specialized computational pipelines to yield useful information. Here, we describe main steps of such a pipeline, and discuss bioinformatic and statistical asp...
Data
Correlation of gene expression patterns in various datasets. A heatmap shows Spearman’s correlation coefficients between microglia activation (log2 fold changes) for samples collected from human, mouse, and rat samples.
Data
Western blot analysis of total extracts from microglia polarized with glioma cells for active components of transforming growth factor beta signaling pathway revealed the increased levels of active, phosphorylated SMAD2 proteins accumulating at 3 and 6 h after glioma-conditioned medium (GCM) treatment. Immunoblots were stripped and re-probed first...
Data
Matrigel assay was performed to determine invasion of different human glioma cells in the presence of SV40 immortalized human microglia. Data are calculated as fold change in relation to basal invasion in the absence of microglia. Matrigel invasion data are calculated as means ± SD, n = 3 and were analyzed by one-sided paired sample t-test; n ≥ 3....
Data
Microarray gene expression validation. Five genes were selected for validation of the microarray gene expression analysis (Tgm2, Cx3cr1, Tgfbi, Tmem37, and Socs2). Expression is presented as delta Ct values in control, glioma-conditioned medium (GCM) LN18, and GCM U87-MG treated for 6 h. Validation was performed on separate experiments n = 4; **p <...
Article
Full-text available
Immune cells accumulating in the microenvironment of malignant tumors are tumor educated and contribute to its growth, progression, and evasion of antitumor immune responses. Glioblastoma (GBM), the common and most malignant primary brain tumor in adults, shows considerable accumulation of resident microglia and peripheral macrophages, and their po...
Conference Paper
Full-text available
Introduction Personalised oncology revolutionises the way how eligible therapies are selected to treat cancer patients. With the help of next-generation sequencing technology, cancer can be understood at the molecular level. This enables clinicians to match cancer patients to drugs that precisely target the driver mutations of the tumour. The found...
Conference Paper
Full-text available
Introduction Glioblastoma (GBM) is the most aggressive primary brain tumour, with a median patient survival of 14 months. Accumulating evidence suggests that glioma stem-like cells (GSCs) are responsible for glioblastoma propagation, recurrence and resistance to therapy. Differentiation therapy is consider as a promising approach to eliminate this...
Article
Full-text available
In glioma, microglia and infiltrating macrophages are exposed to factors that force them to produce cytokines and chemokines, contributing to tumor growth and maintaining a pro-tumorigenic, immunosuppressed microenvironment. We demonstrate that housing glioma-bearing mice in enriched environment (EE) reverts the immunosuppressive phenotype of infil...
Data
Raw data and detailed statistical analysis report. Raw data of Gene Ontology over-representation analysis (Bonferroni corrected p-values <0.05) of the genes that are upregulated in microglia after EE exposure.Image: raw data refer to Figure 1 data.
Article
Full-text available
Glioblastoma (GBM) is the most aggressive primary brain tumor, with ineffective anti-tumor responses and a poor prognosis despite aggressive treatments. GBM immune microenvironment is heterogenous and activation of specific immune populations in GBM is not fully characterized. Reliable animal models are critical for defining mechanisms of anti-tumo...
Chapter
This unit describes a method for determining the accessibility of chromatinized DNA and nucleosome occupancy in the same assay. Enzymatic digestion of chromatin using micrococcal nuclease (MNase) is optimized for liberation, retrieval, and characterization of DNA fragments from chromatin. MNase digestion is performed in a titration series, and the...
Article
Full-text available
Activation of transcription requires alteration of chromatin by complexes that increase the accessibility of nucleosomal DNA. Removing nucleosomes from regulatory sequences has been proposed to play a significant role in activation. We tested whether changes in nucleosome occupancy occurred on the set of genes that is activated by the unfolded prot...
Article
Full-text available
SMARCB1 (also known as SNF5, INI1, and BAF47), a core subunit of the SWI/SNF (BAF) chromatin-remodeling complex, is inactivated in nearly all pediatric rhabdoid tumors. These aggressive cancers are among the most genomically stable, suggesting an epigenetic mechanism by which SMARCB1 loss drives transformation. Here we show that, despite having ind...
Data
Top 1000 regions with highest turnover in ESCs. DOI: http://dx.doi.org/10.7554/eLife.15316.021
Data
Top 1000 regions with highest turnover in NSCs. DOI: http://dx.doi.org/10.7554/eLife.15316.022
Data
Primer sequences. DOI: http://dx.doi.org/10.7554/eLife.15316.026
Data
External datasets used. DOI: http://dx.doi.org/10.7554/eLife.15316.024
Data
Spike-in controls. DOI: http://dx.doi.org/10.7554/eLife.15316.025
Data
Differences in turnover between ESCs and NSCs. DOI: http://dx.doi.org/10.7554/eLife.15316.023
Article
Full-text available
Chromatin accessibility plays a fundamental role in gene regulation. Nucleosome placement, usually measured by quantifying protection of DNA from enzymatic digestion, can regulate accessibility. We introduce a metric that uses micrococcal nuclease (MNase) digestion in a novel manner to measure chromatin accessibility by combining information from s...
Data
Supplementary Figures 1-26 and Supplementary Tables 1-2
Article
Full-text available
Glioblastoma (GBM) is an aggressive malignancy associated with profound host immunosuppression. Microglia and macrophages infiltrating GBM acquire the pro-tumorigenic, M2 phenotype and support tumor invasion, proliferation, survival, angiogenesis and block immune responses both locally and systematically. Mechanisms responsible for immunological de...
Data
Sequences of primers for ChIP-PCR and quantitative PCR used in this work.
Article
Full-text available
Unlabelled: Most neurological diseases are associated with chronic inflammation initiated by the activation of microglia, which produce cytotoxic and inflammatory factors. Signal transducers and activators of transcription (STATs) are potent regulators of gene expression but contribution of particular STAT to inflammatory gene expression and STAT-...
Article
Full-text available
An important step prior to constructing a classifier for a very large data set is feature selection. With many problems it is possible to find a subset of attributes that have the same discriminative power as the full data set. There are many feature selection methods but in none of them are Rough Set models tied up with statistical argumentation....
Article
Full-text available
Signaling pathways belong to a complex system of communication that governs cellular processes. They represent signal transduction from an extracellular stimulus via a receptor to intracellular mediators, as well as intracellular interactions. Perturbations in signaling cascade often lead to detrimental changes in cell function and cause many disea...
Data
An R code used to perform ACST. (R)
Data
This document shows (i) list of analyzed pathways; (ii) results obtained with SPIA, BPA and GSEA; (iii) lists of eliminated.CEL files; (iv) correlations (with p{values) between results obtained for different datasets. (XLS)
Data
Full-text available
Fragments of pathways containing all consistent subgraphs of signifcantly deregulated pathways in both RCC datasets as well as in both BC datasets. Additionally, this file contains also table which contain a summary of results obtained with each of tested methods. (PDF)
Article
JAK (Janus kinase)/STAT (signal transducers and activators of transcription) signaling is involved in the regulation of cell growth, differentiation and apoptosis. Constitutive activation of STATs, in particular STAT3, is observed in a large number of human tumors, including gliomas and may contribute to oncogenesis by stimulating cell proliferatio...
Article
s: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 12-16, 2011; San Francisco, CA Aberrant activation of signal transducer and activator of transcription 3 (STAT3) occurs frequently in diverse human tumors. Constitutively activated STAT3 induces specific target genes that stimulate cell proliferation, preven...
Article
Tuberous sclerosis complex (TSC) is characterized by the formation of benign tumors in many organs (mainly brain, heart, kidneys, skin or lungs) and is often associated with epilepsy, mental retardation and autism. Brain lesions include subependymal giant cell astrocytomas (SEGAs), low-grade tumors of a mixed glioneuronal lineage, which are the maj...
Data
Full-text available
Sequence logos and transcription factors binding to the motifs identified by BN analysis.
Data
Full-text available
Assessment of the normality of the linear regression residua.
Data
Full-text available
The nomenclature of SVD applied to gene expression data.