Biology subjects

Batada, N. N.

Publications and source records attributed to Batada, N. N..

3 recordsLinked to original sources

bioRxiv2021

Systemic influences of mammary cancer on monocytes in mice

There is a growing body of evidence that cancer causes systemic changes. These influences are most evident in the bone marrow and blood, particularly the myeloid compartment. Here we show using mouse models of breast cancer caused by the mammary epithelial expression of the Polyoma middle T antigen that there is an increase in the number of circulating and splenic monocytes. In the circulation, cancer does not affect ratios of classical to non-classical populations monocytes nor their halflives. Single cell RNA sequencing also indicates that cancer does not induce any new monocyte populations. In the bone marrow cancer does not change monocytic progenitor number is unaffected but the proliferation rate of monocytes is higher thus providing an explanation for expansion in the circulating number. Deep RNA sequencing of these monocytic populations reveals cancer causes changes in the classical monocyte compartment with changes evident in bone marrow monocytes but more in the blood suggesting influences in both compartments. Down regulation of interferon type 1 signalling and antigen presentation were the most prominent. Consistent with this analysis down regulated genes are enriched with STAT1/STAT2 binding sites in their promoter, transcription factors required for type 1 interferon signalling. However, these transcriptome changes in mice did not replicate those found in patients with breast cancer. Consequently, mouse models of cancer may be insufficient to study the systemic influences of human cancer.

cancer biology↗

bioRxiv2019

SET8 localization to chromatin flanking DNA damage is dependent on RNF168 ubiquitin ligase

The DNA damage response (DDR) associated post-translational modifications recruit chromatin remodelers, signaling proteins such as 53BP1 and repair factors to chromatin flanking DNA double strand breaks (DSBs) to promote its repair. Although localization of both RNF168 ubiquitin ligase and SET8 methyltransferase at DSBs is essential for 53BP1s recruitment to DSBs, it is unclear if they do so via the same pathways. Here we report that RNF168 mediates SET8s recruitment to DSBs. Depletion of cellular pool of ubiquitin through proteasome inhibition abolished RNF168 and SET8s localization to DNA damage. Knockdown of RNF8 or RNF168 abolished SET8s recruitment to DNA damage. Moreover, RNF168 and SET8 form stable complexes in vivo. Based on these results we propose a model in which SET8, which despite being a pan-chromatin binding protein, can accumulate several folds at chromatin flanking DSBs through tethering to other proteins that specifically localize to chromatin regions with specific modifications.

cell biology↗

bioRxiv2018

Mapping transcriptionally equivalent populations across single cell RNA-seq datasets

The power of single cell RNA sequencing (scRNA-seq) stems from its ability to uncover cell type-dependent phenotypes, which rests on the accuracy of cell type identification. However, resolving cell types within and, thus, comparison of scRNA-seq data across conditions is challenging due to technical factors such as sparsity, low number of cells and batch effect. To address these challenges we developed scID (Single Cell IDentification), which uses the framework of Fishers Linear Discriminant Analysis to identify transcriptionally related cell types between scRNA-seq datasets. We demonstrate the accuracy and performance of scID relative to existing methods on several published datasets. By increasing power to identify transcriptionally similar cell types across datasets, scID enhances investigators ability to extract biological insights from scRNA-seq data.

bioinformatics↗