Identification of Differentially Expressed Hematopoiesis-associated Genes in Term Low Birth Weight Newborns by Systems Genomics Approach

Abstract

Background: Low Birth Weight (LBW) (birth weight <2.5 Kg) newborns are associated with a high risk of infection, morbidity and mortality during their perinatal period. Compromised innate immune responses and inefficient hematopoietic differentiation in term LBW newborns led us to evaluate the gene expression status of hematopoiesis. Materials and Methods: In this study, we compared our microarray datasets of LBW-Normal Birth Weight (NBW) newborns with two reference datasets to identify hematopoietic stem cells genes, and their differential expression in the LBW newborns, by hierarchical clustering algorithm using gplots and RcolorBrewer package in R. Results: Comparative analysis revealed 108 differentially expressed hematopoiesis genes (DEHGs), of which 79 genes were up-regulated, and 29 genes were down-regulated in LBW newborns compared to their NBW counterparts. Moreover, protein-protein interactions, functional annotation and pathway analysis demonstrated that the up-regulated genes were mainly involved in cell proliferation and differentiation, MAPK signaling and Rho GTPases signaling, and the down-regulated genes were engaged in cell proliferation and regulation, immune system regulation, hematopoietic cell lineage and JAK-STAT pathway. The binding of down-regulated genes (LYZ and GBP1) with growth factor GMCSF using docking and MD simulation techniques, indicated that GM-CSF has the potential to alleviate the repressed hematopoiesis in the term LBW newborns. Conclusion: Our study revealed that DEHGs belonged to erythroid and myeloid-specific lineages and may serve as potential targets for improving hematopoiesis in term LBW newborns to help build up their weak immune defense against life-threatening infections.