Biology subjects

Kurukuti, S.

Publications and source records attributed to Kurukuti, S..

4 recordsLinked to original sources

bioRxiv2025

MicroRNA-mRNA Gene Regulatory Circuitry Orchestrates the Epigenetic and Transcriptional Reprogramming from Pluripotency to Murine Mammary Epithelial stem-like-Cells lactogenic differentiation

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression via mRNA degradation or translational repression. While miRNAs are established regulators of development and differentiation, their role in the dynamic mRNA transitions during lactogenic differentiation of mammary epithelial cells remains incompletely characterized. In this study, we profiled miRNA expression across four distinct developmental states: embryonic stem cells (ESCs), and three progressive stages of HC11 murine mammary epithelial differentiation, including undifferentiated growth factor-maintained cells (HC11-N), glucocorticoid-primed cells (HC11-P), and prolactin-induced lactogenic cells (HC11-PRL). By integrating these signatures with parallel mRNA expression profiles, we identified stage-specific miRNA-mRNA regulatory axes. Our analysis revealed miRNAs coordinate networks of transcription factors and epigenetic regulators to shape the lactogenic transcriptome. While ESCs and undifferentiated HC11 cells were characterized by pathways associated with pluripotency and oncogenic signalling, the pregnancy-like priming stage showed enrichment in, neurotrophin signalling. Crucially, the lactation-like state was dominated by PI3K-Akt and mTOR signalling-- critical drivers of epithelial proliferation and milk synthesis. Furthermore, the integration of miRNAs with transcriptional and epigenetic regulators highlighted the modulation of prolactin signalling and extracellular matrix-receptor interactions during lactation. This study provides a comprehensive map of the miRNA-associated post-transcriptional landscape of lactogenesis, offering a mechanistic framework for understanding mammary gland development and associated pathologies.

genomics↗

bioRxiv2021

I-M-150847, a novel GLP-1 and GIP receptor dual agonist, reduces body weight gain and improves glycemic control in the rodent model of type 2 diabetes and obesity.

We report the discovery of a novel unimolecular glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor dual agonist that exhibits potent glycemic control and weight loss in diet-induced obese mice. The dual agonism of GLP-1 and GIP receptor was achieved by replacing the tryptophan cage of exendin-4 with the C-terminal undecapeptide sequence of oxyntomodulin along with a single amino acid substitution from histidine to tyrosine at the amino terminus of the peptide. The structural modification places lysine 30 of the novel incretin agonist in frame with the corresponding lysine residue in the native GIP sequence. The novel incretin receptor dual agonist, named I-M-150847, induces rapid redistribution of GLP-1R at the plasma membrane following activation ensuring the maintenance of the receptor in a sensitized state. I-M-150847 promotes glucose-stimulated insulin exocytosis in cultured pancreatic beta cells and augments insulin-stimulated glucose uptake in mouse adipocytes. Chronic administration of I-M-150847 enhances insulin sensitivity, improves glycemic control, and achieves significant weight loss relative to the control or exendin-4-treated DIO-mice demonstrating the therapeutic efficacy of dual agonist in ameliorating type 2 Diabetes and Obesity. Significance statement.O_LIReplacement of the Trp-cage with the C-terminal oxyntomodulin undecapeptide along with the tyrosine substitution at the amino terminus converts the selective GLP-1R agonist exendin-4 to a novel GLP-1R and GIPR dual agonist I-M-150847. C_LIO_LIThe GLP-1R and GIPR dual agonist I-M-150847 induces the expeditious redistribution of GLP-1R at the plasma membrane following initial activation thereby maintaining the receptor in a sensitized state. C_LIO_LIThe incretin receptor dual agonist I-M-150847 enhances insulin sensitivity and delivers superior glycemic control and weight loss compared to exendin-4 in the rodent model of diabetes and obesity. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=197 HEIGHT=200 SRC="FIGDIR/small/471325v2_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1e27480org.highwire.dtl.DTLVardef@4e88acorg.highwire.dtl.DTLVardef@1eee9e7org.highwire.dtl.DTLVardef@3e41c9_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2018

Biased visibility in HiC datasets marks dynamically regulated condensed and decondensed chromatin states genome-wide.

Proximity ligation based techniques, like HiC, involve restriction digestion followed by ligation of formaldehyde cross-linked chromatin. We showed that the HiC datasets have significant bias due to differential accessibility of chromatin domains to restriction endonucleases. Through analysis of lamina-associated domains (LADs), inactive X-chromosome in mammals and polytene bands in fly, we established that the DNA in condensed chromatin had lesser accessibility to nucleases used in HiC as compared to that in decondensed chromatin. The observed bias was independent of known systematic biases attributed to length and GC content of the restriction fragments and was not appropriately corrected by computational methods. We identified novel condensed domains outside LADs, which were bordered by insulators and were dynamically associated with the developmentally regulated epigenetic and transcriptional states. Our observations suggested that the corrected read counts of existing HiC datasets can be reliably repurposed to study the dynamics of chromatin condensation and decondensation and that the existing HiC datasets should be interpreted with cautions.

genomics↗

bioRxiv2017

Polymorphic Dynamics of Ribosomal Proteins′ Gene Expression during Induced Pluripotency

Factor induced pluripotent stem cells (iPSCs) offer great promise in regenerative medicine. However, accumulating evidence suggests that iPSCs are heterogeneous in comparison with embryonic stem cells (ESCs), and that is attributed to various genetic and epigenetic states of donor cells. In the light of the discovery of cell-type specialized ribosomal protein composition, its role as the cells transit through different stages of reprogramming and when iPSCs differentiate into specialized cell-types has not been explored to understand its influence in the reprogramming and differentiation process and outcome. By re-analyzing the publicly available gene expression datasets among ESCs, various sources of iPSCs and somatic cells and by studying the ribosomal protein gene expression during different stages of reprogramming of somatic cells and different passages of established iPSCs we found distinct patterns of their expression across multiple cell-types. We experimentally validated these results on the cells undergoing reprogramming from human dermal fibroblasts. Finally, by comparing publicly available data from iPSCs, iPSCs derived specialized cells and its in vivo counterparts, we show alterations in ribosomal gene expression during differentiation of specialized cells from iPSCs which may have Implications in the context of ribosomopathies. Our results provide an informatics framework for researchers in efficient generation of iPSCs that are equivalent to ESCs.

developmental biology↗