Biology subjects

Winiarczyk, D.

Publications and source records attributed to Winiarczyk, D..

3 recordsLinked to original sources

bioRxiv2025

The HNF4A Q164X Mutation Impairs Transcriptional Activation in Vitro but Its Heterozygosity Suppresses Liver Tumorigenesis in Vivo

Hepatocyte nuclear factor 4 alpha (HNF4A) is a master regulator of hepatic differentiation and metabolism. Here, we identify and characterize a truncating Q164X mutation that impairs HNF4A transcriptional activity in vitro and causes embryonic lethality when homozygous. Functional assays revealed that the Q164X protein retains nuclear localization but exhibits severely reduced DNA binding and transcriptional activation. CRISPR-generated Q164X mice showed no viable homozygotes, confirming the essential role of HNF4A in early embryogenesis. Unexpectedly, heterozygous Q164X mutants displayed reduced liver tumorigenesis following diethylnitrosamine and high-fat diet treatment, despite downregulation of HNF4A target genes such as ApoB and Hnf1a. These results suggest that partial HNF4A deficiency may trigger compensatory metabolic networks that protect against carcinogenic stress. Collectively, our study establishes Q164X as a loss-of-function HNF4A mutation with paradoxical tumor-suppressive effects in vivo.

cancer biology↗

bioRxiv2025

Protamine sequence determines species-specific nuclear shape and histone retention

Nuclear shape observed after the forced expression of mouse or human Protamine 1 (PRM1) in fibroblasts led us to propose the hypothesis that PRM1 sequence plays an important role in imposing the overall shape of the protaminized nucleus. Comparison of mouse and human PRM1 sequence pointed to cysteines 15 and 29 as potential critical residues in the mouse PRM1 sequence inducing the characteristic mouse "hooked" nuclear sperm shape. To explore this idea, mice with mutations in PRM1 Cys15 and Cys29 were generated. These mice remained fertile with no significant changes in sperm count or protamine expression levels. However, modifications in sperm head shape were observed. Transmission electron microscopy revealed disrupted chromatin condensation in mutant sperm, with several morphological changes and a remarkable increase in histone retention. Overall, the findings suggest that species-specific PRM1 cysteine residue positions are crucial for nuclear shape determination and histone retention in spermatozoa.

developmental biology↗

bioRxiv2019

Urinary proteome of dogs with kidney injury during babesiosis

This study aimed to identify proteins found in the urine of dogs with renal dysfunction leading to acute injury during the natural course of babesiosis (n=10) and to compare them with proteins of a control group (n=10) to reveal any potential biomarkers of renal damage. Pooled urine samples of both groups were separated by 2D electrophoresis (two dimensional electrophoresis), followed by the identification of all proteins using MALDI-TOF mass spectrometry (matrix assisted laser desorption ionization-time of flight). In total, 176 proteins were identified in the urine samples from healthy dogs, and 403 proteins were identified in the urine samples from dogs with babesiosis. Of the 176 proteins, 146 were assigned exclusively to healthy dogs, and 373 of the 403 proteins were assigned exclusively to dogs with babesiosis; 30 proteins were common to both groups. Characteristic analysis of the 373 proteins found in dogs with babesiosis led to the isolation of 8 proteins associated with 10 metabolic pathways that were attributed to immune and inflammatory response development. Furthermore, it was hypothesized that the epithelial-mesenchymal transition might play an important role in mechanisms underlying pathological renal tissue changes during babesiosis, as indicated by a causal relationship network built by combining 5 of the 10 selected metabolic pathways and 4 of the 8 proteins associated with these pathways. These included cadherins, gonadotropin releasing hormone receptors, inflammatory responses mediated by chemokine and cytokine signalling pathways, integrins, interleukin and TGF-{beta} (transforming growth factor {beta}) pathways. These pathways were linked by interleukin-13, bone morphogenetic protein 7, 2(1) collagen, and FER tyrosine kinase, which are potential damage biomarkers during babesiosis in dogs that might be assigned to early renal injury.

pathology↗