title: Maturation-associated gene expression profiles along normal human bone marrow monopoiesis.
abstract: Human monopoiesis is a tightly coordinated process which starts in the bone marrow (BM) haematopoietic stem cell (HSC) compartment and leads to the production of circulating blood mature monocytes. Although mature monocytes/macrophages have been extensively studied in both normal or inflammatory conditions, monopoiesis has only been assessed in vitro and in vivo animal models, due to low frequency of the monocytic precursors in the normal human BM. Here we investigated the transcriptional profile along normal human BM monopoiesis. Five distinct maturation-associated stages of monocytic precursors were identified and isolated from (fresh) normal human BM through fluorescence-activated cell sorting, and the gene expression profile (GEP) of each monocytic precursor subset was analysed by DNA-oligonucleotide microarrays. Overall, >6000 genes (18% of the genes investigated) were expressed in ≥1 stage of BM monopoiesis at stable or variable amounts, showing early decrease in cell proliferation with increased levels of expression of genes linked with cell differentiation. The here-defined GEP of normal human BM monopoiesis might contribute to better understand monocytic differentiation and the identification of novel monocytic candidate markers, while also providing a frame of reference for the study of monocytic maturation in both neoplastic and non-neoplastic disease conditions involving monocytic precursor cells.
authors.affiliation: Clinical Medicine Postgraduate Programme, College of Medicine, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro, Brazil.|Cytometry Service, Institute of Paediatrics and Puericulture Martagão Gesteira (IPPMG), UFRJ, Rio de Janeiro, Brazil.
authors.forename: Fabiana V
authors.initials: FV
authors.lastname: Mello
authors.affiliation: Clinical Medicine Postgraduate Programme, College of Medicine, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro, Brazil.|Cytometry Service, Institute of Paediatrics and Puericulture Martagão Gesteira (IPPMG), UFRJ, Rio de Janeiro, Brazil.|Pharmacy Service INCa, Rio de Janeiro, Brazil.
authors.forename: Liliane R
authors.initials: LR
authors.lastname: Alves
authors.affiliation: Clinical Medicine Postgraduate Programme, College of Medicine, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro, Brazil.
authors.forename: Marcelo G P
authors.initials: MG
authors.lastname: Land
authors.affiliation: Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Cristina
authors.initials: C
authors.lastname: Teodósio
authors.affiliation: Department of Medicine and Cytometry Service (Nucleus), Cancer Research Centre (IBMCC, USAL-CSIC), Institute for Biomedical Research of Salamanca (IBSAL), University of Salamanca (USAL), Salamanca, Spain.
authors.forename: María-Luz
authors.initials: ML
authors.lastname: Sanchez
authors.affiliation: Department of Medicine and Cytometry Service (Nucleus), Cancer Research Centre (IBMCC, USAL-CSIC), Institute for Biomedical Research of Salamanca (IBSAL), University of Salamanca (USAL), Salamanca, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Bárcena
authors.affiliation: CEFET-RJ, Rio de Janeiro, Brazil.
authors.forename: Rodrigo T
authors.initials: RT
authors.lastname: Peres
authors.affiliation: COPPE-PESC Rio de Janeiro Federal University (UFRJ), Rio de Janeiro, Brazil.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Pedreira
authors.affiliation: Clinical Medicine Postgraduate Programme, College of Medicine, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro, Brazil.|Cytometry Service, Institute of Paediatrics and Puericulture Martagão Gesteira (IPPMG), UFRJ, Rio de Janeiro, Brazil.
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Costa
authors.affiliation: Department of Medicine and Cytometry Service (Nucleus), Cancer Research Centre (IBMCC, USAL-CSIC), Institute for Biomedical Research of Salamanca (IBSAL), University of Salamanca (USAL), Salamanca, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
mesh_terms: D000293:Adolescent; D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002648:Child; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D055815:Young Adult
keywords: bone marrow monocytic maturation; gene expression profile; microarray; normal human monopoiesis; transcriptome