Biology subjects

Kattler, K.

Publications and source records attributed to Kattler, K..

4 recordsLinked to original sources

bioRxiv2023

Mutual regulation of transcriptomes between pneumocytes and fibroblasts mediates alveolar regeneration

Alveolar type 2 (AT2) and club cells are part of the stem cell niche of the lung and their differentiation is required for pulmonary homeostasis and tissue regeneration. A disturbed crosstalk between fibroblasts and epithelial cells contributes to the loss of lung structure in chronic lung diseases. Therefore, it is important to understand how fibroblasts and lung epithelial cells interact during regeneration. Here we analyzed the interaction of fibroblasts and the alveolar epithelium modelled in air-liquid interface cultures. Single-cell transcriptomics showed that co-cultivation with fibroblasts leads to increased expression of type 2 markers in pneumocytes, activation of regulons associated with maintenance of alveolar type 2 cells, and trans-differentiation of club cells towards pneumocytes. This was accompanied by an intensified transepithelial barrier. Vice versa, activation of NF{kappa}B pathways and the CEBPB regulon as well as the expression of IL-6 and other differentiation factors (e.g. FGFs) were increased in fibroblasts co-cultured with epithelial cells. Recombinant IL-6 enhanced epithelial barrier formation. Therefore, in our co-culture model, regulatory loops were identified by which lung epithelial cells mediate regeneration and differentiation of the alveolar epithelium in a cooperative manner with the mesenchymal compartment.

cell biology↗

bioRxiv2019

Unique and assay specific features of NOMe-, ATAC- and DNase I-seq data

Chromatin accessibility maps are important for the functional interpretation of the genome. Here, we systematically analysed assay specific differences between DNase I-Seq, ATAC-Seq and NOMe-Seq in a side by side experimental and bioinformatic setup. We observe that most prominent nucleosome depleted regions (NDRs, e.g. in promoters) are roboustly called by all three or at least two assays. However we also find a high proportion of assay specific NDRs that are often "called" by only one of the assays. We show evidence that these assay specific NDRs are indeed genuine open chromatin sites and contribute important information for accurate gene expression prediction. While technically ATAC-Seq and DNAse I-Seq provide a high NDR calling rate for relatively low sequencing costs in comparison to NOMe-Seq, NOMe-Seq singles out as it provides a multitude of information: it allows to not only detect NDRs but also endogenous DNA methylation, genome wide segmentation into heterochromatic A/B domains and local phasing of nucleosomes outside of NDRs. In summary our comparison strongly suggest to consider assay specific differences for the experimental desgin and for generalized and comparative functional interpretations.

genomics↗

bioRxiv2018

Integrative analysis of single cell expression data reveals distinct regulatory states in bidirectional promoters

BackgroundBidirectional promoters (BPs) are prevalent in eukaryotic genomes. However, it is poorly understood how the cell integrates different epigenomic information, such as transcription factor (TF) binding and chromatin marks, to drive gene expression at BPs. Single cell sequencing technologies are revolutionizing the field of genome biology. Therefore, this study focuses on the integration of single cell RNA-seq data with bulk ChIP-seq and other epigenetics data, for which single cell technologies are not yet established, in the context of BPs.\n\nResultsWe performed integrative analyses of novel human single cell RNA-seq (scRNA-seq) data with bulk ChIP-seq and other epigenetics data. scRNA-seq data revealed distinct transcription states of BPs that were previously not recognized. We find associations between these transcription states to distinct patterns in structural gene features, DNA accessibility, histone modification, DNA methylation and TF binding profiles.\n\nConclusionsOur results suggest that a complex interplay of all of these elements is required to achieve BP-specific transcriptional output in this specialized promoter configuration. Further, our study implies that novel statistical methods can be developed to deconvolute masked subpopulations of cells measured with different bulk epigenomic assays using scRNA-seq data.

genomics↗

bioRxiv2018

Partially methylated domains are hallmarks of a cell specific epigenome topology

BackgroundPartially methylated domains, PMDs, are extended regions in the genome exhibiting a reduced average DNA-methylation level. PMDs cover gene-poor and transcriptionally inactive regions and tend to be heterochromatic. Here, we present a first comprehensive comparative analysis of PMDs across more than 190 WGBS methylomes of human and mouse cells providing a deep insight into structural and functional features associated with PMDs.\n\nResultsPMDs are ubiquitous signatures covering up to 75% of the genome in human and mouse cells irrespective of their tissue or cell origin. Additionally, each cell type comes with a distinct set of specific PMDs, and genes expressed in such PMDs show a strong cell type effect. Demethylation strength varies in PMDs with a tendency towards a more pronounced effect in differentiating and replicating cells. The strongest demethylation is observed in highly proliferating and immortal cancer cell lines. A decrease of DNA-methylation within PMDs tends to be linked to an increase in heterochromatic histone marks and a decrease of gene expressions. Characteristic combinations of heterochromatic signatures in PMDs are linked to domains of early, middle and late DNA-replication.\n\nConclusionPMDs are prominent signatures of long-range epigenomic organization. Integrative analysis identifies PMDs as important general, lineage- and cell-type specific topological features. PMD changes are hallmarks of cell differentiation. Demethylation of PMDs combined with increased heterochromatic marks is a feature linked to enhanced cell proliferation. In combination with broad histone marks PMDs demarcate distinct domains of late DNA-replication.

bioinformatics↗