Biology subjects

Bostan, H.

Publications and source records attributed to Bostan, H..

4 recordsLinked to original sources

bioRxiv2026

Increased chromatin accessibility following 1α,25-dihydroxyvitamin D3 treatment in human endometrial stromal cells

Vitamin D signaling has recognized roles in female reproductive physiology, but its effects at the chromatin level in endometrial stromal cells are still unclear. Here, we investigated how the active form of vitamin D, 1,25-dihydroxyvitamin D3, or calcitriol, influences the accessible chromatin landscape of human endometrial stromal cells. Assay for transposase-accessible chromatin using sequencing (ATAC-seq) was performed on T-HESCs treated with either a vehicle or 1,25(OH)2D3. Ligand treatment increased overall chromatin accessibility, shown by higher ATAC-seq signal intensity, while causing only minor changes in the total number of called peaks. Peak annotation revealed that accessible regions were spread across both promoter-proximal and distal genomic areas. Integrating this data with CUT&RUN and RNA sequencing showed that most vitamin D-responsive cistromic modifications and transcripts were linked to nearby open chromatin, though fewer were associated with regions that were significantly differentially accessible. These results suggest that 1,25(OH)2D3-dependent transcription mainly occurs within a permissive, pre-accessible chromatin environment. This study offers new evidence that active vitamin D influences the epigenomic landscape of human endometrial stromal cells, establishing the chromatin-based molecular response to a chemically-defined VDR ligand, 1,25(OH)2D3, relevant to stromal differentiation and preparation for decidualization. HighlightsO_LIFirst evidence suggesting the direct impact of active vitamin D, 1,25-dihydroxyvitamin D3, 1,25(OH)2D3, enhanced the signal intensity of chromatin accessibility in human endometrial stromal cells C_LIO_LIMost accessible chromatin regions were shared between vehicle and ligand-treated human endometrial stromal cells C_LIO_LI1,25(OH)2D3-responsive transcription occurs largely within pre-accessible chromatin in human endometrial stromal cells C_LIO_LIAssay for transposase-accessible chromatin sequencing (ATAC-seq) defines a chromatin-level pharmacologic response to a chemically defined VDR ligand in human endometrial stromal cells C_LI

molecular biology↗

bioRxiv2026

Comparative whole-genome analyses of articular chondrocytes and skin fibroblasts reveal distinct genome instability landscapes in mesenchymal cell types

DNA damage lesions can result in mutations and genome rearrangements that are associated with cellular aging and diseases. The landscape of somatic mutations in individual tissue and cell types are dictated by their unique physiological states, cellular functions, mutagenic exposures, and efficiency of DNA repair. Articular chondrocytes and skin fibroblasts are two cell types of mesodermal origin with distinct exposure to internal and external sources of DNA damage. While somatic genome instability features of skin fibroblasts have been well detailed, knowledge about mechanisms underlying genome changes in chondrocytes is scarce. Here, we took a whole-genome sequencing approach to evaluate the load, sources, and patterns of genome changes in 18 primary human chondrocyte clones from donors with and without osteoarthritis (OA). Findings in chondrocyte clones largely agreed with a recent study of 100 single-cell sequenced chondrocytes. We compared genome changes in chondrocytes with clonally-expanded human skin fibroblasts sequenced in our previous studies. We demonstrated that skin fibroblasts show a higher burden of somatic mutations, with an increased rate of mutation accumulation per cell division. Motif-centered analyses of mutation catalogues identified only endogenous sources of mutations in chondrocytes, as opposed to skin fibroblasts which also showed a heavy burden of UV-induced mutations. Spontaneous deamination of meCpG and mutagenesis by exposure to small epoxides and SN2 electrophiles showed higher mutagenic activities in chondrocytes compared to skin fibroblasts. Chondrocytes showed ubiquitous prevalence of indels in homonucleotide runs of [≥]5 bases, while skin fibroblasts showed high contributions of UV-associated deletions of [≥]5bp not in repeats. Structural variants in rearrangement hotspots colocalized with human common fragile sites in skin fibroblasts, but not in chondrocytes. Together, our study comprehensively recorded genome instability features in chondrocytes and highlighted the unique mutagenesis landscapes of two mesenchymal cell types.

genetics↗

bioRxiv2026

APOBEC3A is the predominant global editor of cytosines in human mRNAs and in single-strand RNA viruses

APOBEC cytidine deaminases can convert cytosines to uracils in DNA as well as in RNA. The knowledge of DNA deamination motifs preferred by individual APOBECs revealed APOBEC3A as a major source of hypermutation in cancer. However, the extent and relative contribution of specific APOBECs into RNA editing remains unclear as their preferred RNA-editing motifs have not been defined. Here, using a parallel DNA and RNA sequencing strategy, coupled with motif-centered statistical analyses, we sought to identify mRNA edits and diagnostic editing motifs in yeast and human cells overexpressing individual APOBEC enzymes. This approach revealed a prevailing global enrichment for the uCg trinucleotide motif with even greater preference to the motifs cytosines located in 3 base of a loop within a hairpin-loop secondary structure when APOBEC3A, but not any other tested APOBEC, was overexpressed. Further analysis revealed the APOBEC3A-like diagnostic motif enrichment in editing calls from human cancers and blood cells. The APOBEC3A-like editing motif also prevailed in the RNA genomes of SARS-CoV-2 pandemic isolates, as well as in infectious persistent rubella viruses, and in polioviruses emerging from live-attenuated vaccine strains. Together, our results indicate that APOBEC3A is the predominant global APOBEC RNA editor with a potential to impact cell physiology and viral evolution.

genetics↗

bioRxiv2023

Systematic assessment of long-read RNA-seq methods for transcript identification and quantification

AbstractThe Long-read RNA-Seq Genome Annotation Assessment Project (LRGASP) Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. The consortium generated over 427 million long-read sequences from cDNA and direct RNA datasets, encompassing human, mouse, and manatee species, using different protocols and sequencing platforms. These data were utilized by developers to address challenges in transcript isoform detection and quantification, as well as de novo transcript isoform identification. The study revealed that libraries with longer, more accurate sequences produce more accurate transcripts than those with increased read depth, whereas greater read depth improved quantification accuracy. In well-annotated genomes, tools based on reference sequences demonstrated the best performance. When aiming to detect rare and novel transcripts or when using reference-free approaches, incorporating additional orthogonal data and replicate samples are advised. This collaborative study offers a benchmark for current practices and provides direction for future method development in transcriptome analysis.

genomics↗