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Nicotine exposure during differentiation causes inhibition of N-myc expression

Ben-Yehudah, A and Campanaro, BM and Wakefield, LM and Kinney, TN and Brekosky, J and Eisinger, VM and Castro, CA and Carlisle, DL (2013) Nicotine exposure during differentiation causes inhibition of N-myc expression. Respiratory Research, 14 (1). ISSN 1465-9921

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Abstract

Background: The ability of chemicals to disrupt neonatal development can be studied using embryonic stem cells (ESC). One such chemical is nicotine. Prenatal nicotine exposure is known to affect postnatal lung function, although the mechanisms by which it has this effect are not clear. Since fibroblasts are a critical component of the developing lung, providing structure and secreting paracrine factors that are essential to epithelialization, this study focuses on the differentiation of ESC into fibroblasts using a directed differentiation protocol.Methods: Fibroblasts obtained from non-human primate ESC (nhpESC) differentiation were analyzed by immunohistochemistry, immunostaining, Affymetrix gene expression array, qPCR, and immunoblotting.Results: Results of these analyses demonstrated that although nhpESCs differentiate into fibroblasts in the presence of nicotine and appear normal by some measures, including H&E and SMA staining, they have an altered gene expression profile. Network analysis of expression changes demonstrated an over-representation of cell-cycle related genes with downregulation of N-myc as a central regulator in the pathway. Further investigation demonstrated that cells differentiated in the presence of nicotine had decreased N-myc mRNA and protein expression and longer doubling times, a biological effect consistent with downregulation of N-myc.Conclusions: This study is the first to use primate ESC to demonstrate that nicotine can affect cellular differentiation from pluripotency into fibroblasts, and in particular, mediate N-myc expression in differentiating ESCs. Given the crucial role of fibroblasts throughout the body, this has important implications for the effect of cigarette smoke exposure on human development not only in the lung, but in organogenesis in general. © 2013 Ben-Yehudah et al.; licensee BioMed Central Ltd.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Ben-Yehudah, A
Campanaro, BM
Wakefield, LM
Kinney, TN
Brekosky, J
Eisinger, VM
Castro, CAcac131@pitt.eduCAC131
Carlisle, DLdlc4@pitt.eduDLC4
Centers: Other Centers, Institutes, or Units > Magee-Women's Research Institute
Date: 5 November 2013
Date Type: Publication
Journal or Publication Title: Respiratory Research
Volume: 14
Number: 1
DOI or Unique Handle: 10.1186/1465-9921-14-119
Schools and Programs: School of Medicine > Neurological Surgery
School of Medicine > Obstetrics, Gynecology, and Reproductive Sciences
Refereed: Yes
ISSN: 1465-9921
Date Deposited: 02 Dec 2016 16:11
Last Modified: 25 Jun 2018 13:57
URI: http://d-scholarship.pitt.edu/id/eprint/29660

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