Biology subjects

Chera, S.

Publications and source records attributed to Chera, S..

3 recordsLinked to original sources

bioRxiv2025

MODY mutations in transcription factors HNF1A and HNF1B affect the production of interferon signaling proteins: evidence at the proteome level

We investigated the proteomic consequences of MODY-associated mutations in the transcription factors HNF1A and HNF1B using two cell line models. Quantitative label-free mass spectrometry, employing both data-dependent and data-independent acquisition methods, revealed consistent suppression of energy metabolism and interferon signaling pathways. Pathway and protein interaction analyses confirmed these findings. In cells with the HNF1A frameshift mutation, several predicted transcriptional targets, including A1CF, were significantly downregulated. These results reinforce the link between HNF1A/HNF1B function and mitochondrial activity as well as innate immune signaling, providing a foundation for further mechanistic studies and causal inference research.

systems biology↗

bioRxiv2021

Islet transplantation tolerance in animals with defined histocompatibility and diabetes

Advances in organ transplantation benefit from development of genetically inbred animal strains with defined histocompatibility and cell-specific markers to distinguish donor and host cell subsets. For studies of pancreatic islet transplantation tolerance in diabetes, an invariant method to ablate host {beta} cells and induce diabetes would provide an immense additional advantage. Here we detail development and use of B6 RIP-DTR mice, an immunocompetent line permitting diabetes induction with 100% penetrance. This inbred line is homozygous for the C57BL/6J major histocompatibility complex (MHC) haplotype and expresses the mutant CD45.1 allele in the hematopoietic lineage. {beta} cell-specific expression of a high-affinity receptor for diphtheria toxin (DT) permits experimental {beta} cell ablation and diabetes induction after DT administration. Diabetes reversal for over one year was achieved after transplantation with congenic C57BL/6J islets, but not with MHC-mismatched BALB/c islets, which were rapidly rejected. In summary, the generation of a C57BL/6J congenic line harboring the CD45.1 allele and Ins2-HBEGF transgene should advance studies of islet transplantation tolerance and mechanisms to improve islet engraftment and function, thereby optimizing development of cell replacement strategies for diabetes mellitus.

immunology↗

bioRxiv2019

Encapsulation boosts islet-cell signature in differentiating human induced pluripotent stem cells via integrin signalling

Cell replacement therapies hold great therapeutic potential. Nevertheless, our knowledge of the mechanisms governing the developmental processes is limited, impeding the quality of differentiation protocols. Generating insulin-expressing cells in vitro is no exception, with the guided series of differentiation events producing heterogeneous cell populations that display mixed pancreatic islet phenotypes and immaturity. The achievement of terminal differentiation ultimately requires the in vivo transplantation of, usually, encapsulated cells. Here we show the impact of cell confinement on the pancreatic islet signature during the guided differentiation of alginate encapsulated human induced pluripotent stem cells (hiPSCs). Our results show that encapsulation improves differentiation by significantly reshaping the proteome landscape of the cells towards an islet-like signature. Pathway analysis is suggestive of integrins transducing the encapsulation effect into intracellular signalling cascades promoting differentiation. These analyses provide a molecular framework for understanding the confinement effects on hiPSCs differentiation while confirming its importance for this process.

molecular biology↗