title: Meta-analysis of microarray studies reveals a novel hematopoietic progenitor cell signature and demonstrates feasibility of inter-platform data integration.
abstract: Microarray-based studies of global gene expression (GE) have resulted in a large amount of data that can be mined for further insights into disease and physiology. Meta-analysis of these data is hampered by technical limitations due to many different platforms, gene annotations and probes used in different studies. We tested the feasibility of conducting a meta-analysis of GE studies to determine a transcriptional signature of hematopoietic progenitor and stem cells. Data from studies that used normal bone marrow-derived hematopoietic progenitors was integrated using both RefSeq and UniGene identifiers. We observed that in spite of variability introduced by experimental conditions and different microarray platforms, our meta-analytical approach can distinguish biologically distinct normal tissues by clustering them based on their cell of origin. When studied in terms of disease states, GE studies of leukemias and myelodysplasia progenitors tend to cluster with normal progenitors and remain distinct from other normal tissues, further validating the discriminatory power of this meta-analysis. Furthermore, analysis of 57 normal hematopoietic stem and progenitor cell GE samples was used to determine a gene expression signature characteristic of these cells. Genes that were most uniformly expressed in progenitors and at the same time differentially expressed when compared to other normal tissues were found to be involved in important biological processes such as cell cycle regulation and hematopoiesis. Validation studies using a different microarray platform demonstrated the enrichment of several genes such as SMARCE, Septin 6 and others not previously implicated in hematopoiesis. Most interestingly, alpha-integrin, the only common stemness gene discovered in a recent comparative murine analysis (Science 302(5644):393) was also enriched in our dataset, demonstrating the usefulness of this analytical approach.
authors.affiliation: Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Davendra
authors.initials: D
authors.lastname: Sohal
authors.forename: Andrew
authors.initials: A
authors.lastname: Yeatts
authors.forename: Kenny
authors.initials: K
authors.lastname: Ye
authors.forename: Andrea
authors.initials: A
authors.lastname: Pellagatti
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Perry
authors.initials: P
authors.lastname: Pahanish
authors.forename: Yongkai
authors.initials: Y
authors.lastname: Mo
authors.forename: Tushar
authors.initials: T
authors.lastname: Bhagat
authors.forename: John
authors.initials: J
authors.lastname: Mariadason
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Boultwood
authors.forename: Ari
authors.initials: A
authors.lastname: Melnick
authors.forename: John
authors.initials: J
authors.lastname: Greally
authors.forename: Amit
authors.initials: A
authors.lastname: Verma
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D001854:Bone Marrow Cells / Q000502:physiology; D002478:Cells, Cultured / Q000473:pathology / Q000502:physiology; D030541:Databases, Genetic; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D012016:Reference Values
chemical_list: D015703:Antigens, CD