The School of Natural Sciences
Toxicant-disrupted transcriptional regulation skews osteoblastogenesis
Nicole R. Sparks, Ph.D.
Department of Molecular, Cell and Systems Biology
University of California, Riverside
Tuesday, June 1st, 2021
To Zoom in, please use this link: https://ucmerced.zoom.us/j/85143133934
Birth defects that affect skeletal tissues are a major public health concern causing a life-long impact on the individual and their families. Insults from environmental chemicals can disrupt the dynamic genetic regulatory processes that can manifest skeletal disorders of the skull or short/long bones. Yet, the link between environmental exposure and molecular alterations that lead to a skeletal birth defect are least understood. This study investigated transcriptional regulators that are associated with impaired skeletal development caused by toxicant exposure. Osteogenically differentiating human embryonic stem cells (hESCs) were exposed to the popular Camel brand of tobacco products and selected test chemicals that inhibited osteoblast differentiation and devised an in vitro model to assess skeletal developmental toxicity. Toxicant exposure altered skeletal fate commitment determined by RNA (T, EOMES, CDX1/2) and miRNA (miR92b, miR145, miR520a, and miR526b) sequencing. Gene ontology of the differentially expressed genes and miRNAs indicated defects in skeletal system development, neural crest developmental/differentiation, and mesoderm development. These toxicant-induced transcriptional signatures reflect crucial roles of genes and miRNAs during skeletal development and can serve as an indicator for skeletal birth defects.
Dr. Nicole Sparks did her bachelor’s degree at La Sierra University. Then went on for her master’s degree at CSU San Bernardino, followed by her PhD at UC Riverside. Dr. Sparks is a Postdoctoral Researcher in the Cell, Molecular and Systems Biology Department at the University of California Riverside, and a recipient of the inaugural NIH K99/R00 mosaic award through NIEHS and a previous UC Chancellor’s Postdoctoral Fellow. Her research focuses on stem cell fate changes due to toxicant exposure that associates with skeletal birth defects under the mentorship of Dr. Nicole zur Nieden. Specifically, she is focused on how transcriptional regulators, necessary for proper bone differentiation, are negatively impacted by toxicant exposure, leading to unwanted differentiation defects.
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