Biology subjects

Pranty, A. I.

Publications and source records attributed to Pranty, A. I..

3 recordsLinked to original sources

bioRxiv2024

Identification of novel evolutionarily conserved genes and pathways in human and mouse musculoskeletal progenitors

The axial skeletal system and skeletal muscles of the vertebrates arise from somites, the blocks of tissues flanking both sides of the neural tube. The progenitors of Somites, called the Presomitic Mesoderm (PSM) reside at the posterior end of a developing embryo. Most of our understanding about these two early developmental stages comes from the studies on chick and mouse, and in the recent past, there have been a few studies on human. Here, we have analysed and compared the RNA-sequencing data of PSM and somite tissues from Mouse and Human. The functional and pathway enrichment analysis identified the key Hub-genes that are evolutionarily conserved in the PSM and the somites of both the organisms that include 23 multifunctional genes likely to be associated with different developmental disorders in humans. Our analysis revealed that NOTCH, WNT, MAPK, BMP, Calcium, ErbB, cGMP-PKG, RAS and RAP1 signaling pathways are conserved in both human and mouse during the development of PSM and Somites. Furthermore, we validated the expression of representative conserved candidates in the hESCs-derived PSM and somite cells (NOG, BMP2, BMP7, BMP5, HES5 and MEF2C). Taken together, our study identifies putative gene interactions and pathways that are conserved across the mouse and human genomes, which may potentially have crucial roles in human PSM and somite development.

bioinformatics↗

bioRxiv2024

Hemozoin induces Malaria via activation of DNA damage, p38 MAPK and Neurodegenerative Pathways in Human iPSC-derived Neuronal Model of Cerebral Malaria

Malaria caused by Plasmodium falciparum infection results in severe complications including cerebral malaria (CM), in which approximately 30% of patients end up with neurological sequelae. Sparse in vitro cell culture-based experimental models which recapitulate the molecular basis of CM in humans has impeded progress in our understanding of its etiology. This study employed healthy human induced pluripotent stem cells (iPSCs) derived neuronal cultures stimulated with hemozoin (HMZ)-the malarial toxin as a model for CM. Secretome, qRT-PCR, Metascape, and KEGG pathway analyses were conducted to assess elevated proteins, genes, and pathways. Neuronal cultures treated with HMZ showed enhanced secretion of interferon-gamma (IFN-{gamma}), interleukin (IL)1-beta (IL-1{beta}), IL-8 and IL-16. Enrichment analysis revealed malaria, positive regulation of cytokine production and positive regulation of mitogen-activated protein kinase (MAPK) cascade which confirm inflammatory response to HMZ exposure. KEGG assessment revealed up-regulation of malaria, MAPK and neurodegenerative diseases-associated pathways which corroborates findings from previous studies. Additionally, HMZ induced DNA damage in neurons. This study has unveiled that exposure of neuronal cultures to HMZ, activates molecules and pathways similar to that observed in CM and neurodegenerative diseases. Furthermore, our model is an alternative to rodent experimental models of CM.

neuroscience↗

bioRxiv2023

Unconjugated bilirubin induces neuro-inflammation in an induced pluripotent stem cell-derived cortical organoid model of Crigler Najjar Syndrome

Bilirubin-induced neurological damage (BIND), which is also known as Kernicterus, occurs as a consequence of defects in the bilirubin conjugation machinery, thus resulting in unconjugated bilirubin (UCB) to cross the blood-brain barrier (BBB) and accumulation. Severe hyperbilirubinemia can be caused by a mutation within the UGT1A1 encoding gene. This mutation has a direct contribution towards bilirubin conjugation leading to Kernicterus as a symptom of Crigler Najjar Syndromes (CNS1, CNS2) and Gilbert syndrome, which results in permanent neurological sequelae. In this comparative study, we used human induced pluripotent stem cells (hiPSCs)-derived 3D-brain organoids to model BIND in vitro and unveil the molecular basis of the detrimental effects of UCB in the developing human brain. hiPSC-derived from healthy and CNS patients were differentiated into day-20 brain organoids, these were then stimulated with 200nM UCB. Analyses at 24- and 72-hrs post-treatment point at UCB-induced neuro-inflammation in both cell lines. Transcriptome and associated KEGG and Gene Ontology analyses unveiled activation of distinct inflammatory pathways such as cytokine-cytokine receptor interaction, MAPK signaling, calcium signaling, NF{kappa}B activation. Furthermore, both mRNA expression and secretome analysis confirmed an upregulation of pro-inflammatory cytokines such as IL6 and IL8 upon UCB stimulation. In summary, this novel study has provided insights into how a human iPSC-derived 3D-brain organoid model can serve as a prospective platform for studying the etiology of BIND-Kernicterus.

neuroscience↗