bioRxiv Science⌕ Search

Biology subjects

Batan, D.

Publications and source records attributed to Batan, D..

4 recordsLinked to original sources

Integration and harmonization of cell shape images for generative modeling

As cell imaging grows in scale, precision, and complexity, data integration and harmonization become increasingly important for studying cell-material interactions. Quantitative understanding of how cells respond to mechanical cues, such as substrate stiffness and topography, is often limited by differences in experimental conditions and imaging formats. This study presents a framework that combines compact, interpretable cell shape models with generative artificial intelligence to harmonize 2D and 3D immunofluorescent datasets within defined experimental contexts. By efficiently capturing morphology and associated biological features, the approach enables generation of realistic synthetic cells, including rare or intermediate phenotypes, to augment machine-learning analyses and support scalable in silico studies. This work advances data-driven investigation of cellular responses to biomaterial-derived mechanical cues.

bioengineering↗

PTEN Regulates Myofibroblast Activation in Valvular Interstitials Cells based on Subcellular Localization

Aortic valve stenosis (AVS) is characterized by altered mechanics of the valve leaflets, which disrupts blood flow through the aorta and can cause left ventricle hypotrophy. These changes in the valve tissue result in activation of resident valvular interstitial cells (VICs) into myofibroblasts, which have increased levels of SMA in their stress fibers. The persistence of VIC myofibroblast activation is a hallmark of AVS. In recent years, the tumor suppressor gene phosphatase and tensin homolog (PTEN) has emerged as an important player in the regulation of fibrosis in various tissues (e.g., lung, skin), which motivated us to investigate PTEN as a potential protective factor against matrix-induced myofibroblast activation in VICs. In aortic valve samples from humans, we found high levels of PTEN in healthy tissue and low levels of PTEN in diseased tissue. Then, using pharmacological inducers to treat VIC cultures, we observed PTEN overexpression prevented stiffness-induced myofibroblast activation, whereas genetic and pharmacological inhibition of PTEN further activated myofibroblasts. We also observed increased nuclear PTEN localization in VICs cultured on stiff matrices, and nuclear PTEN also correlated with smaller nuclei, altered expression of histones and a quiescent fibroblast phenotype. Together, these results suggest that PTEN not only suppresses VIC activation, but functions to promote quiescence, and could serve as a potential pharmacological target for the treatment of AVS.

cell biology↗

Automated Prediction of Fibroblast Phenotypes Using Mathematical Descriptors of Cellular Features

Fibrosis is caused by pathological activation of resident fibroblasts to myofibroblasts that leads to aberrant tissue stiffening and diminished function of affected organs with limited pharmacological interventions. Despite the prevalence of myofibroblasts in fibrotic tissue, existing methods to grade fibroblast phenotypes are typically subjective and qualitative, yet important for screening of new therapeutics. Here, we develop mathematical descriptors of cell morphology and intracellular structures to identify quantitative and interpretable cell features that capture the fibroblast-to-myofibroblast phenotypic transition in immunostained images. We train and validate models on features extracted from over 2,500 primary heart valve interstitial cells (VICs) and test their predictive performance on VICs treated with the small molecule drug 5-azacytidine, which inhibited myofibroblast activation. Collectively, this work introduces an analytical framework that unveils key features associated with distinct fibroblast phenotypes via quantitative image analysis and is broadly applicable for high-throughput screening assays of candidate treatments for fibrotic diseases.

bioengineering↗

Development of a riboswitch-based platform for live cell imaging of RNAs in mammalian cells

RNAs directly regulate a vast array of critical cellular processes, emphasizing the need for robust approaches to fluorescently tag and track RNAs in living cells. Here, we develop an RNA imaging platform using the cobalamin riboswitch as an RNA tag and a series of probes containing cobalamin as a fluorescence quencher. This highly modular Riboglow platform leverages different color fluorescent dyes, linkers and riboswitch RNA tags to elicit fluorescent turn-on upon binding RNA. We demonstrate the ability of two different Riboglow probes to track mRNA and small non-coding U RNA in live mammalian cells. A direct side-by-side comparison revealed that Riboglow outperformed the dye binding aptamer Broccoli and performed on par with the current gold standard RNA imaging system, the MS2-fluorescent protein system, while featuring a much smaller RNA tag. Together, the versatility of the Riboglow platform and ability to track diverse RNAs suggest broad applicability for a variety of imaging approaches.\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=85 SRC=\"FIGDIR/small/199240_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (29K):\norg.highwire.dtl.DTLVardef@11b5e3borg.highwire.dtl.DTLVardef@1c78fc0org.highwire.dtl.DTLVardef@aeba74org.highwire.dtl.DTLVardef@1531e3a_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗