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Maternal Obesity Is Associated with Transcriptional Changes in Cord Blood Mononuclear Cells
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A1434 - Maternal Obesity Is Associated with Transcriptional Changes in Cord Blood Mononuclear Cells
Author Block: B. Turturice, L. Tussing-Humphreys, M. Koenig, D. Perkins, P. W. Finn; University of Illinois at Chicago, Chicago, IL, United States.
Rationale: Maternal obesity has been identified as a risk factor for several childhood diseases, including asthma and wheezing. The mechanism through which maternal obesity mediates long-term disease risk is not well understood. Therefore, the goal of this study was to assess potential transcriptional changes early in life that are associated with changes in maternal body mass index (BMI).
Methods: Previously published microarray datasets of cord blood mononuclear cells (CBMCs) were assessed using a consensus network approach to identify modules of co-expressed genes whose expression was associated with maternal BMI. To identify transcriptional drivers of response we constructed transcription factor-gene networks using genes from modules that associated with maternal BMI. To validate these findings, a cohort was assembled and mRNA-seq was performed on CBMCs from offspring with mothers with normal (n=26) and obese (n=25) BMI.
Results: Five modules of co-expressed genes were identified to be significantly associated with changes in maternal adiposity. Three of these modules were negatively associated with increasing adiposity and the other two were positively associated with increasing adiposity. The modules that were negatively associated with increasing adiposity were enriched for genes in pathways involved in positive regulation of innate immune responses, response to virus, and signal transduction. The modules that were positively associated with increasing adiposity were enriched for genes in pathways involved in RNA metabolism and electron transport chain. Transcription factor-gene networks predicted that genes positively associated with maternal obesity were driven by transcription factors: HIF1a, SIRT1, STAT6, HMGN1, HMGB2, EIF2AK2, and ZNF148. Genes negatively associated with maternal obesity were predicted to be driven by transcription factors: XBP1, RXRa, and TFCP2.
Conclusions: Maternal obesity is associated with large transcriptional changes in cord blood mononuclear cells. These changes are in genes responsible for immune responses to microbes and energy metabolism. In studying multiple populations, we have identified candidate genes and transcription factors related to maternal obesity. These findings may provide a link between metabolic changes and immune responses.
Author Block: B. Turturice, L. Tussing-Humphreys, M. Koenig, D. Perkins, P. W. Finn; University of Illinois at Chicago, Chicago, IL, United States.
Rationale: Maternal obesity has been identified as a risk factor for several childhood diseases, including asthma and wheezing. The mechanism through which maternal obesity mediates long-term disease risk is not well understood. Therefore, the goal of this study was to assess potential transcriptional changes early in life that are associated with changes in maternal body mass index (BMI).
Methods: Previously published microarray datasets of cord blood mononuclear cells (CBMCs) were assessed using a consensus network approach to identify modules of co-expressed genes whose expression was associated with maternal BMI. To identify transcriptional drivers of response we constructed transcription factor-gene networks using genes from modules that associated with maternal BMI. To validate these findings, a cohort was assembled and mRNA-seq was performed on CBMCs from offspring with mothers with normal (n=26) and obese (n=25) BMI.
Results: Five modules of co-expressed genes were identified to be significantly associated with changes in maternal adiposity. Three of these modules were negatively associated with increasing adiposity and the other two were positively associated with increasing adiposity. The modules that were negatively associated with increasing adiposity were enriched for genes in pathways involved in positive regulation of innate immune responses, response to virus, and signal transduction. The modules that were positively associated with increasing adiposity were enriched for genes in pathways involved in RNA metabolism and electron transport chain. Transcription factor-gene networks predicted that genes positively associated with maternal obesity were driven by transcription factors: HIF1a, SIRT1, STAT6, HMGN1, HMGB2, EIF2AK2, and ZNF148. Genes negatively associated with maternal obesity were predicted to be driven by transcription factors: XBP1, RXRa, and TFCP2.
Conclusions: Maternal obesity is associated with large transcriptional changes in cord blood mononuclear cells. These changes are in genes responsible for immune responses to microbes and energy metabolism. In studying multiple populations, we have identified candidate genes and transcription factors related to maternal obesity. These findings may provide a link between metabolic changes and immune responses.
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