Biology subjects

Virk, R.

Publications and source records attributed to Virk, R..

3 recordsLinked to original sources

bioRxiv2025

Turning blood to brain cells: a plasma mediated reprograming model

The lack of effective stem cell protocols for generating personalized neurovascular niches poses a critical challenge in precision medicine. While iPSC-based methods are explored, their clinical use is hindered by high costs, long timelines, and cancer risks. Recent advancements in plasma-driven differentiation, using circulating monocytes, offer a promising solution as they can be reprogrammed into neuron-like, endothelial-like, and hematopoietic cells without genetic manipulation, by inducing growth factors mediated transdifferentiation. Vasculature is integral to neurodevelopment, with early blood supply transitioning from the perineural to intrinsic vascular plexus, driven by neuro-hematovascular signaling. The choroid plexus selectively transports proteins and growth factors from blood to CSF, supporting neural proliferation and differentiation. Building on these insights, we leveraged the innate reprograming potential of blood-derived cells to generate neuro-hematovascular niches using a novel PITTRep methodology, devoid of transgene and growth factor mediated transdifferentiation opening new avenues for regenerative and investigative neurovascular studies.

cell biology↗

bioRxiv2020

Exposure of mammary cells to lipid activates gene expression changes associated with ER-negative breast cancer via chromatin remodeling.

Improved understanding of local breast biology that favors the development of estrogen receptor negative (ER-) breast cancer (BC) would foster better prevention strategies. We have previously shown that overexpression of specific lipid metabolism genes is associated with the development of ER- BC. We now report results of exposure of MCF-10A cells and mammary organoids to representative medium- and long-chain polyunsaturated fatty acids. This exposure caused a dynamic and profound change in gene expression, accompanied by changes in chromatin packing density, chromatin accessibility and histone posttranslational modifications (PTMs). We identified 38 metabolic reactions that showed significantly increased activity, including reactions related to one-carbon metabolism. Among these reactions are those that produce S-adenosyl-L-methionine for histone PTMs. Utilizing both an in-vitro model and samples from women at high risk for ER- BC, we show that lipid exposure engenders gene expression, signaling pathway activation, and histone marks associated with the development of ER- BC.

cancer biology↗

bioRxiv2020

Nanoscale Chromatin Imaging and Analysis (nano-ChIA) platform bridges 4-D chromatin organization with molecular function

In eukaryotic cells, chromatin structure is linked to transcription processes through the regulation of genome organization. Extending across multiple length-scales - from the nucleosome to higher-order three-dimensional structures - chromatin is a dynamic system which evolves throughout the lifetime of a cell. However, no individual technique can fully elucidate the behavior of chromatin organization and its relation to molecular function at all length- and timescales at both a single-cell and a cell population level. Herein, we present a multi-technique nanoscale Chromatin Imaging and Analysis (nano-ChIA) platform that bridges electron tomography and optical superresolution imaging of chromatin conformation and transcriptional processes, with resolution down to the level of individual nucleosomes, with high-throughput, label-free analysis of chromatin packing and its dynamics in live cells. Utilizing nano-ChIA, we observed that chromatin is localized into spatially separable packing domains, with an average diameter of around 200 nm, sub-Mb genomic size, and an internal fractal structure. The chromatin packing behavior of these domains is directly influenced by active gene transcription. Furthermore, we demonstrated that the chromatin packing domain structure is correlated among progenitor cells and all their progeny, indicating that the organization of chromatin into fractal packing domains is heritable across cell division. Further studies employing the nano-ChIA platform have the potential to provide a more coherent picture of chromatin structure and its relation to molecular function.

genomics↗