Login Register Cart 0
Generic placeholder image

Current Genomics

Editor-in-Chief

ISSN (Print): 1389-2029
ISSN (Online): 1875-5488

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

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

Author(s): Sakshi Singh, Vinay K. Singh and Geeta Rai*

Volume 20, Issue 7, 2019

Page: [469 - 482] Pages: 14

DOI: 10.2174/1389202920666191203123025

Price: $65

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.

Keywords: LBW and NBW newborns, hematopoietic-associated genes, genomics, molecular docking, systems genomics approach, neutropenia.

« Previous Next »
Graphical Abstract

[1]
Acheson, E.D. Hospital morbidity in early life in relation to certain maternal and foetal characteristics and events at delivery. Br. J. Prev. Soc. Med., 1965, 19(4), 164-173.
[http://dx.doi.org/10.1136/jech.19.4.164] [PMID: 5891786]
[2]
Ashworth, A. Effects of intrauterine growth retardation on mortality and morbidity in infants and young children. Eur. J. Clin. Nutr., 1998, 52(Suppl. 1), S34-S41.
[PMID: 9511018]
[3]
Valero De Bernabé, J.; Soriano, T.; Albaladejo, R.; Juarranz, M.; Calle, M.E.; Martínez, D.; Domínguez-Rojas, V. Risk factors for low birth weight: a review. Eur. J. Obstet. Gynecol. Reprod. Biol., 2004, 116(1), 3-15.
[http://dx.doi.org/10.1016/j.ejogrb.2004.03.007] [PMID: 15294360]
[4]
Sankar, M.J.; Neogi, S.B.; Sharma, J.; Chauhan, M.; Srivastava, R.; Prabhakar, P.K.; Khera, A.; Kumar, R.; Zodpey, S.; Paul, V.K. State of newborn health in India. J. Perinatol., 2016, 36(s3), S3-S8.
[http://dx.doi.org/10.1038/jp.2016.183] [PMID: 27924104]
[5]
Changes in cause-specific neonatal and 1-59-month child mortality in India from 2000 to 2015: a nationally representative survey. Lancet, 2017, 390(10106), 1972-1980.
[http://dx.doi.org/10.1016/S0140-6736(17)32162-1] [PMID: 28939096]
[6]
Siva, S.K.N. Extremely low birth weight infant. Pediatrics: cardiac disease and critical care medicine, 2014.http://emedicine.medscape.com/article/979717-overview
[7]
McCall, E.M.; Alderdice, F.A.; Halliday, H.L.; Jenkins, J.G.; Vohra, S. Interventions to prevent hypothermia at birth in preterm and/or low birthweight infants. Cochrane Database Syst. Rev., 2008, (1) CD004210
[http://dx.doi.org/10.1002/14651858.CD004210.pub3] [PMID: 18254039]
[8]
Witek-Janusek, L.; Shareef, M.J.; Mathews, H.L. Reduced lymphocyte-mediated antifungal capacity in high-risk infants. J. Infect. Dis., 2002, 186(1), 129-133.
[http://dx.doi.org/10.1086/341293] [PMID: 12089675]
[9]
Roberts, I.; Murray, N.A. Neonatal thrombocytopenia: causes and management. Arch. Dis. Child. Fetal Neonatal Ed., 2003, 88(5), F359-F364.
[http://dx.doi.org/10.1136/fn.88.5.F359] [PMID: 12937037]
[10]
Christensen, R.D.; Henry, E.; Wiedmeier, S.E.; Stoddard, R.A.; Sola-Visner, M.C.; Lambert, D.K.; Kiehn, T.I.; Ainsworth, S. Thrombocytopenia among extremely low birth weight neonates: data from a multihospital healthcare system. J. Perinatol., 2006, 26(6), 348-353.
[http://dx.doi.org/10.1038/sj.jp.7211509] [PMID: 16642027]
[11]
Maheshwari, A. Neutropenia in the newborn. Curr. Opin. Hematol., 2014, 21(1), 43-49.
[http://dx.doi.org/10.1097/MOH.0000000000000010] [PMID: 24322487]
[12]
Chandra, R.K. Fetal malnutrition and postnatal immunocompetence. Am. J. Dis. Child., 1975, 129(4), 450-454.
[PMID: 165712]
[13]
Singh, M.; Manerikar, S.; Malaviya, A.N. Premawathi; Gopalan, R.; Kumar, R. Immune status of low birth weight babies. Indian Pediatr., 1978, 15(7), 563-567.
[PMID: 569131]
[14]
Saha, K.; Kaur, P.; Srivastava, G.; Chaudhury, D.S. A six-months’ follow-up study of growth, morbidity and functional immunity in low birth weight neonates with special reference to intrauterine growth retardation in small-for-gestational-age infants. J. Trop. Pediatr., 1983, 29(5), 278-282.
[http://dx.doi.org/10.1093/tropej/29.5.278] [PMID: 6685774]
[15]
Ferguson, A.C. Prolonged impairment of cellular immunity in children with intrauterine growth retardation. J. Pediatr., 1978, 93(1), 52-56.
[http://dx.doi.org/10.1016/S0022-3476(78)80599-X] [PMID: 77323]
[16]
Chatrath, R.; Saili, A.; Jain, M.; Dutta, A.K. Immune status of full-term small-for-gestational age neonates in India. J. Trop. Pediatr., 1997, 43(6), 345-348.
[http://dx.doi.org/10.1093/tropej/43.6.345] [PMID: 9476456]
[17]
Walter, A.W. Perinatal Anemia. MSD MANUAL Professional Version, 2017.http://www.msdmanuals.com/en-nz/professional/pediatrics/perinatal-hematologic-disorders/perinatal-anemia19Sept 2017.
[18]
Singh, V.V.; Chauhan, S.K.; Rai, R.; Kumar, A.; Singh, S.M.; Rai, G. Decreased pattern recognition receptor signaling, interferon-signature, and bactericidal/permeability-increasing protein gene expression in cord blood of term low birth weight human newborns. PLoS One, 2013, 8(4) e62845
[http://dx.doi.org/10.1371/journal.pone.0062845] [PMID: 23626859]
[19]
Strohsnitter, W.C.; Savarese, T.M.; Low, H.P.; Chelmow, D.P.; Lagiou, P.; Lambe, M.; Edmiston, K.; Liu, Q.; Baik, I.; Noller, K.L.; Adami, H.O.; Trichopoulos, D.; Hsieh, C.C. Correlation of umbilical cord blood haematopoietic stem and progenitor cell levels with birth weight: implications for a prenatal influence on cancer risk. Br. J. Cancer, 2008, 98(3), 660-663.
[http://dx.doi.org/10.1038/sj.bjc.6604183] [PMID: 18256588]
[20]
Kotowski, M.; Safranow, K.; Kawa, M.P.; Lewandowska, J.; Klos, P.; Dziedziejko, V.; Paczkowska, E.; Czajka, R.; Celewicz, Z.; Rudnicki, J.; Machaliński, B. Circulating hematopoietic stem cell count is a valuable predictor of prematurity complications in preterm newborns. BMC Pediatr., 2012, 12, 148.
[http://dx.doi.org/10.1186/1471-2431-12-148] [PMID: 22985188]
[21]
Wisgrill, L.; Schüller, S.; Bammer, M.; Berger, A.; Pollak, A.; Radke, T.F.; Kögler, G.; Spittler, A.; Helmer, H.; Husslein, P.; Gortner, L. Hematopoietic stem cells in neonates: any differences between very preterm and term neonates? PLoS One, 2014, 9(9) e106717
[http://dx.doi.org/10.1371/journal.pone.0106717] [PMID: 25181353]
[22]
Podestà, M.; Bruschettini, M.; Cossu, C.; Sabatini, F.; Dagnino, M.; Romantsik, O.; Spaggiari, G.M.; Ramenghi, L.A.; Frassoni, F. Preterm cord blood contains a higher proportion of immature hematopoietic progenitors compared to term samples. PLoS One, 2015, 10(9) e0138680
[http://dx.doi.org/10.1371/journal.pone.0138680] [PMID: 26417990]
[23]
Romano, O.; Peano, C.; Tagliazucchi, G.M.; Petiti, L.; Poletti, V.; Cocchiarella, F.; Rizzi, E.; Severgnini, M.; Cavazza, A.; Rossi, C.; Pagliaro, P.; Ambrosi, A.; Ferrari, G.; Bicciato, S.; De Bellis, G.; Mavilio, F.; Miccio, A. Transcriptional, epigenetic and retroviral signatures identify regulatory regions involved in hematopoietic lineage commitment. Sci. Rep., 2016, 6, 24724.
[http://dx.doi.org/10.1038/srep24724] [PMID: 27095295]
[24]
Dircio-Maldonado, R.; Flores-Guzman, P.; Corral-Navarro, J.; Mondragón-García, I.; Hidalgo-Miranda, A.; Beltran-Anaya, F.O.; Cedro-Tanda, A.; Arriaga-Pizano, L.; Balvanera-Ortiz, O.; Mayani, H. Functional integrity and gene expression profiles of human cord blood-derived hematopoietic stem and progenitor cells generated in vitro. Stem Cells Transl. Med., 2018, 7(8), 602-614.
[http://dx.doi.org/10.1002/sctm.18-0013] [PMID: 29701016]
[25]
Gonçalves, J.P.; Madeira, S.C.; Oliveira, A.L. BiGGEsTS: integrated environment for biclustering analysis of time series gene expression data. BMC Res. Notes, 2009, 2, 124.
[http://dx.doi.org/10.1186/1756-0500-2-124] [PMID: 19583847]
[26]
Seo, J.; Gordish-Dressman, H.; Hoffman, E.P. An interactive power analysis tool for microarray hypothesis testing and generation. Bioinformatics, 2006, 22(7), 808-814.
[http://dx.doi.org/10.1093/bioinformatics/btk052] [PMID: 16418236]
[27]
Metsalu, T.; Vilo, J. ClustVis: a web tool for visualizing clustering of multivariate data using Principal Component Analysis and heatmap. Nucleic Acids Res., 2015, 43(W1), W566-W570.
[http://dx.doi.org/10.1093/nar/gkv468] [PMID: 25969447]
[28]
Szklarczyk, D.; Franceschini, A.; Wyder, S.; Forslund, K.; Heller, D.; Huerta-Cepas, J.; Simonovic, M.; Roth, A.; Santos, A.; Tsafou, K.P.; Kuhn, M.; Bork, P.; Jensen, L.J.; von Mering, C. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res., 2015, 43(Database issue), D447-D452.
[http://dx.doi.org/10.1093/nar/gku1003] [PMID: 25352553]
[29]
Jones, P.; Binns, D.; Chang, H.Y.; Fraser, M.; Li, W.; McAnulla, C.; McWilliam, H.; Maslen, J.; Mitchell, A.; Nuka, G.; Pesseat, S.; Quinn, A.F.; Sangrador-Vegas, A.; Scheremetjew, M.; Yong, S.Y.; Lopez, R.; Hunter, S. InterProScan 5: genome-scale protein function classification. Bioinformatics, 2014, 30(9), 1236-1240.
[http://dx.doi.org/10.1093/bioinformatics/btu031] [PMID: 24451626]
[30]
Pagni, M.; Ioannidis, V.; Cerutti, L.; Zahn-Zabal, M.; Jongeneel, C.V.; Hau, J.; Martin, O.; Kuznetsov, D.; Falquet, L. MyHits: improvements to an interactive resource for analyzing protein sequences. Nucleic Acids Res., 2007, 35, W433-W437.
[http://dx.doi.org/10.1093/nar/gkm352] [PMID: 17545200]
[31]
Huang, D.W.; Sherman, B.T.; Tan, Q.; Collins, J.R.; Alvord, W.G.; Roayaei, J.; Stephens, R.; Baseler, M.W.; Lane, H.C.; Lempicki, R.A. The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists. Genome Biol., 2007, 8(9), R183.
[http://dx.doi.org/10.1186/gb-2007-8-9-r183] [PMID: 17784955]
[32]
Supek, F.; Bošnjak, M.; Škunca, N.; Šmuc, T. REVIGO summarizes and visualizes long lists of gene ontology terms. PLoS One, 2011, 6(7) e21800
[http://dx.doi.org/10.1371/journal.pone.0021800] [PMID: 21789182]
[33]
Kanehisa, M.; Goto, S.; Sato, Y.; Furumichi, M.; Tanabe, M. KEGG for integration and interpretation of large-scale molecular data sets. Nucleic Acids Res., 2012, 40(Database issue), D109-D114.
[http://dx.doi.org/10.1093/nar/gkr988] [PMID: 22080510]
[34]
Croft, D.; O’Kelly, G.; Wu, G.; Haw, R.; Gillespie, M.; Matthews, L.; Caudy, M.; Garapati, P.; Gopinath, G.; Jassal, B.; Jupe, S.; Kalatskaya, I.; Mahajan, S.; May, B.; Ndegwa, N.; Schmidt, E.; Shamovsky, V.; Yung, C.; Birney, E.; Hermjakob, H.; D’Eustachio, P.; Stein, L. Reactome: a database of reactions, pathways and biological processes. Nucleic Acids Res., 2011, 39(Database issue), D691-D697.
[http://dx.doi.org/10.1093/nar/gkq1018] [PMID: 21067998]
[35]
Kozakov, D.; Hall, D.R.; Xia, B.; Porter, K.A.; Padhorny, D.; Yueh, C.; Beglov, D.; Vajda, S. The ClusPro web server for protein-protein docking. Nat. Protoc., 2017, 12(2), 255-278.
[http://dx.doi.org/10.1038/nprot.2016.169] [PMID: 28079879]
[36]
Mura, C.; McCrimmon, C.M.; Vertrees, J.; Sawaya, M.R. An introduction to biomolecular graphics. PLOS Comput. Biol., 2010, 6(8) e1000918
[http://dx.doi.org/10.1371/journal.pcbi.1000918] [PMID: 20865174]
[37]
Abraham, M.J.; Murtola, T.; Schulz, R.; Páll, S.; Smith, J.C.; Hess, B.; Lindahl, E. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX, 2015, 1-2, 19-25.
[http://dx.doi.org/10.1016/j.softx.2015.06.001]
[38]
Oostenbrink, C.; Villa, A.; Mark, A.E.; van Gunsteren, W.F. A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force-field parameter sets 53A5 and 53A6. J. Comput. Chem., 2004, 25(13), 1656-1676.
[http://dx.doi.org/10.1002/jcc.20090] [PMID: 15264259]
[39]
Brott, A.S.; Clarke, A.J. Peptidoglycan O-Acetylation as a Virulence Factor: Its effect on lysozyme in the innate immune system. Antibiotics (Basel), 2019, 8(3) E94
[http://dx.doi.org/10.3390/antibiotics8030094] [PMID: 31323733]
[40]
Nordmann, A.; Wixler, L.; Boergeling, Y.; Wixler, V.; Ludwig, S. A new splice variant of the human guanylate-binding protein 3 mediates anti-influenza activity through inhibition of viral transcription and replication. FASEB J., 2012, 26(3), 1290-1300.
[http://dx.doi.org/10.1096/fj.11-189886] [PMID: 22106366]
[41]
Ushach, I.; Zlotnik, A. Biological role of granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on cells of the myeloid lineage. J. Leukoc. Biol., 2016, 100(3), 481-489.
[http://dx.doi.org/10.1189/jlb.3RU0316-144R] [PMID: 27354413]
[42]
Gao, J.; Graves, S.; Koch, U.; Liu, S.; Jankovic, V.; Buonamici, S.; El Andaloussi, A.; Nimer, S.D.; Kee, B.L.; Taichman, R.; Radtke, F.; Aifantis, I. Hedgehog signaling is dispensable for adult hematopoietic stem cell function. Cell Stem Cell, 2009, 4(6), 548-558.
[http://dx.doi.org/10.1016/j.stem.2009.03.015] [PMID: 19497283]
[43]
Lim, Y.; Matsui, W. Hedgehog signaling in hematopoiesis. Crit. Rev. Eukaryot. Gene Expr., 2010, 20(2), 129-139.
[http://dx.doi.org/10.1615/CritRevEukarGeneExpr.v20.i2.30] [PMID: 21133842]
[44]
Richter, J.; Traver, D.; Willert, K. The role of Wnt signaling in hematopoietic stem cell development. Crit. Rev. Biochem. Mol. Biol., 2017, 52(4), 414-424.
[http://dx.doi.org/10.1080/10409238.2017.1325828] [PMID: 28508727]
[45]
Rawlings, J.S.; Rosler, K.M.; Harrison, D.A. The JAK/STAT signaling pathway. J. Cell Sci., 2004, 117(Pt 8), 1281-1283.
[http://dx.doi.org/10.1242/jcs.00963] [PMID: 15020666]
[46]
Miyamoto, T.; Iwasaki, H.; Reizis, B.; Ye, M.; Graf, T.; Weissman, I.L.; Akashi, K. Myeloid or lymphoid promiscuity as a critical step in hematopoietic lineage commitment. Dev. Cell, 2002, 3(1), 137-147.
[http://dx.doi.org/10.1016/S1534-5807(02)00201-0] [PMID: 12110174]
[47]
Geest, C.R.; Coffer, P.J. MAPK signaling pathways in the regulation of hematopoiesis. J. Leukoc. Biol., 2009, 86(2), 237-250.
[http://dx.doi.org/10.1189/jlb.0209097] [PMID: 19498045]
[48]
Guilliams, M.; Ginhoux, F.; Jakubzick, C.; Naik, S.H.; Onai, N.; Schraml, B.U.; Segura, E.; Tussiwand, R.; Yona, S. Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat. Rev. Immunol., 2014, 14(8), 571-578.
[http://dx.doi.org/10.1038/nri3712] [PMID: 25033907]
[49]
Peters, C.W.; Kruse, U.; Pollwein, R.; Grzeschik, K.H.; Sippel, A.E. The human lysozyme gene. Sequence organization and chromosomal localization. Eur. J. Biochem., 1989, 182(3), 507-516.
[http://dx.doi.org/10.1111/j.1432-1033.1989.tb14857.x] [PMID: 2546758]
[50]
Ye, M.; Iwasaki, H.; Laiosa, C.V.; Stadtfeld, M.; Xie, H.; Heck, S.; Clausen, B.; Akashi, K.; Graf, T. Hematopoietic stem cells expressing the myeloid lysozyme gene retain long-term, multilineage repopulation potential. Immunity, 2003, 19(5), 689-699.
[http://dx.doi.org/10.1016/S1074-7613(03)00299-1] [PMID: 14614856]
[51]
Kitaguchi, T.; Kawakami, K.; Kawahara, A. Transcriptional regulation of a myeloid-lineage specific gene lysozyme C during zebrafish myelopoiesis. Mech. Dev., 2009, 126(5-6), 314-323.
[http://dx.doi.org/10.1016/j.mod.2009.02.007] [PMID: 19275935]
[52]
de Bruin, A.M.; Voermans, C.; Nolte, M.A. Impact of interferon-γ on hematopoiesis. Blood, 2014, 124(16), 2479-2486.
[http://dx.doi.org/10.1182/blood-2014-04-568451] [PMID: 25185711]
[53]
Bai, S.; Chen, T.; Deng, X. Guanylate-binding protein 1 promotes migration and invasion of human periodontal ligament stem cells. Stem Cells Int., 2018, 2018 6082956
[http://dx.doi.org/10.1155/2018/6082956] [PMID: 30622567]
[54]
Taira, T.; Maëda, J.; Onishi, T.; Kitaura, H.; Yoshida, S.; Kato, H.; Ikeda, M.; Tamai, K.; Iguchi-Ariga, S.M.; Ariga, H. AMY-1, a novel C-MYC binding protein that stimulates transcription activity of C-MYC. Genes Cells, 1998, 3(8), 549-565.
[http://dx.doi.org/10.1046/j.1365-2443.1998.00206.x] [PMID: 9797456]
[55]
Wilson, A.; Murphy, M.J.; Oskarsson, T.; Kaloulis, K.; Bettess, M.D.; Oser, G.M.; Pasche, A.C.; Knabenhans, C.; Macdonald, H.R.; Trumpp, A. c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation. Genes Dev., 2004, 18(22), 2747-2763.
[http://dx.doi.org/10.1101/gad.313104] [PMID: 15545632]
[56]
García-Bermúdez, J.; Cuezva, J.M. The ATPase Inhibitory Factor 1 (IF1): A master regulator of energy metabolism and of cell survival. Biochim. Biophys. Acta, 2016, 1857(8), 1167-1182.
[http://dx.doi.org/10.1016/j.bbabio.2016.02.004] [PMID: 26876430]
[57]
Hardonnière, K.; Saunier, E.; Lemarié, A.; Fernier, M.; Gallais, I.; Héliès-Toussaint, C.; Mograbi, B.; Antonio, S.; Bénit, P.; Rustin, P.; Janin, M.; Habarou, F.; Ottolenghi, C.; Lavault, M.T.; Benelli, C.; Sergent, O.; Huc, L.; Bortoli, S.; Lagadic-Gossmann, D. The environmental carcinogen benzo[a]pyrene induces a Warburg-like metabolic reprogramming dependent on NHE1 and associated with cell survival. Sci. Rep., 2016, 6, 30776.
[http://dx.doi.org/10.1038/srep30776] [PMID: 27488617]
[58]
Roessler, E.; Ermilov, A.N.; Grange, D.K.; Wang, A.; Grachtchouk, M.; Dlugosz, A.A.; Muenke, M. A previously unidentified amino-terminal domain regulates transcriptional activity of wild-type and disease-associated human GLI2. Hum. Mol. Genet., 2005, 14(15), 2181-2188.
[http://dx.doi.org/10.1093/hmg/ddi222] [PMID: 15994174]

Rights & Permissions Print Cite
Article Metrics
30
© 2024 Bentham Science Publishers | Privacy Policy