Global Gene Expression Profile of Human Bone Marrow before and after Hydroxyurea Administration in Sickle Cell Anemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3750-3750
Author(s):  
Flavia C. Costa ◽  
Anderson F. Cunha ◽  
Andre Fattori ◽  
Tarcisio S. Peres ◽  
Gustavo G.L. Costa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Sickle Cell ◽  
Calcium Binding ◽  
Human Bone ◽  
Differentially Expressed ◽  
Human Bone Marrow ◽  
P Value ◽  
Clinical Evolution ◽  
New Genes

Abstract The levels of HbF in sickle cell disease (SCD) can be increased by pharmacological agents such as hydroxyurea (HU), which has been shown to reduce the frequency of pain crises, hospitalizations and acute chest events requiring blood transfusions in adults with SCD. However, there is some evidence to suggest that some SCD patients show benefits from HU treatment without increase in their HbF levels. Thus, the molecular mechanism by which HU increases HbF levels and improves the clinical evolution in SCD remains unclear. This study aims to provide the global gene profile of human bone marrow of a homozygous patient three months before beginning treatment and after the initial administration of HU and to investigate groups of differentially expressed genes that could be involved in the pathways by which HU improves the clinical evolution in SCD. Using the Serial Analysis of Gene Expression (SAGE) technique, two libraries, before HU administration (HbS profile) and after HU administration (HbSHU) were performed. A total of 47.192 and 46.697 tags were analyzed for the HbS and HbSHU profiles and represented 15.735 and 15.901 distinct tags, respectively. Among these, 4.151 and 3.817 tags were no match tags that could represent new genes that remain to be identified. When both profiles were compared, 518 transcripts were determined to have statistically significant differential levels of expression (P value < 0.05). The functional annotation of transcripts, according to the Gene Ontology Consortium, showed that the categories of binding and structural molecule activity were up-regulated following HU treatment. For example, genes associated with nucleic acid binding such as Signal Transducer and Activator of Transcription 5 A, v-fos FBJ murine osteosarcoma viral oncogene homolog, Early Growth Response 1 and several ribosomal and zinc finger proteins were induced by HU treatment. Conversely, the transporter activity category was down regulated by HU treatment. Genes associated with oxygen transporter activity and other genes associated with ion binding, like S100 calcium binding protein A8 (calgranulin A) and transferrin were found to be down regulated by HU treatment. Taken together, these results strongly suggest that HU produces a significant change in the expression of bone marrow cells. Future studies of these described genes that are differentially expressed during HU treatment may contribute to further the understanding of the mechanism by which HbF acts in SCD and improves the clinical evolution of the disease. The description of new genes involved in these pathways may also represent a potential tool to identify new targets for the therapy of SCD.

scholarly journals Maturation-associated gene expression profiles during normal human bone marrow erythropoiesis

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Fabiana V. Mello ◽  
Marcelo G. P. Land ◽  
Elaine. S. Costa ◽  
Cristina Teodósio ◽  
María-Luz Sanchez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Normal Human ◽  
Normal Human Bone Marrow

scholarly journals Differential gene expression profiling of human bone marrow-derived mesenchymal stem cells during adipogenic development

BMC Genomics ◽  
2011 ◽  
Vol 12 (1) ◽  
pp. 461 ◽  
Author(s):  
Adriane Menssen ◽  
Thomas Häupl ◽  
Michael Sittinger ◽  
Bruno Delorme ◽  
Pierre Charbord ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Gene Expression Profiling ◽  
Differential Gene Expression ◽  
Expression Profiling ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Differential Gene

scholarly journals An Oxygen Transport Model of Human Bone Marrow for Hemolytic Sickle Cell Anemia

2010 ◽  
pp. 7-13
Author(s):  
MA Islam ◽  
R Kumar
Keyword(s):  
Bone Marrow ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Chemical Engineering ◽  
Transport Model ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Hemoglobin Molecule ◽  
Cellular Components

The human bone marrow (BM) is a complicated tissue with intricate vascular and heterogeneousextravascular (tissue) architecture. Oxygen is an important modulator of differentiation and proliferationof the BM hematopoietic cells under normal and pathological conditions. Currently, due to theinaccessibility of the BM, it is not possible to measure the spatial distribution of the oxygen tension(concentration) levels in the tissue. Thus, the present treatise utilizes mathematical modeling to offer agreater insight on the effects of oxygen on the BM cellular components. Here, we present simulationresults that are correlated with known in vivo data of BM along with proposing a model for the two statedescription of allosteric hemoglobin molecule under hemolytic sickle cell anemia condition of BM.Journal of Chemical Engineering Vol.ChE 24 2006 7-13

Meta-Transcriptome of Bone Marrow Stem Cells Demonstrates Platform and Lab Dependant Variability in Gene Expression and Reveals a Novel Set of Enriched Genes.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4189-4189
Author(s):  
Davendra Sohal ◽  
Andrew Yeatts ◽  
Joanna Opalinska ◽  
Li Zhou ◽  
Perry Pahanish ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Bone Marrow ◽  
Expression Patterns ◽  
Bone Marrow Stem Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Gene Expression Patterns ◽  
Expression Studies ◽  
Gene Expression Studies

Abstract While microarray analysis of global gene expression yields enormous amounts of data, there are concerns about standardization and validity of findings. Consequently, we wanted to determine the variability in gene expression studies of human bone marrow in the literature and study the factors that account for these differences. We also wanted to determine if certain genes were consistently and differentially enriched in human bone marrow stem cells. A total of 64 individual datasets were collected from gene expression omnimbus (GEO) database for our analysis (2001–2006). Most of the datasets had been used as controls in studies of hematological malignancies. 13 datasets were hybridized to the Affymetrix U95 chip, 38 analyzed by the Affymetrix human U133A chip and 13 by the U133 plus 2.0 platform. RNA for these studies was derived from purified normal CD34+ cells in 48 cases and from unsorted normal bone marrow mononuclear cells in 16 cases. To merge data from different platforms, we converted individual probe Sequence_ids to RefSeq gene IDs and analyzed them by SAS (SAS Institute, Cary, NC) and Arrayassist software package (Stratagene©). A total of 23686 unique gene IDs were obtained for analysis after the data were normalized, and a KNN algorithm was used to fill the gaps in the data. Our results reveal that there is marked variability in gene expression patterns in this cohort. The data sets clustered together primarily on the basis of the laboratory that performed the assays. (Hierarchical clustering based on average Euclidean distances). Clustering was further defined by the type of chip/platform used for the analysis. Interestingly, the similarity between CD34+ sorted and ununsorted whole BM samples was greater than interplatform similarity between the same phenotypes of cells examined. Notwithstanding the variability in gene expression, there were a novel set of genes that were differentially enriched in all 64 samples. These genes included transcription factors (Kruppel like factor 6), translational proteins (eukaryotic translation initiation factor 4A, isoform 1, ribosomal proteins) and other proteins not previously implicated in hematopoeisis (guanine nucleotide binding protein (GNAS), Calnexin, HLA associated proteins, dUTP pryophosphatase etc.) Mouse homologues of several of these proteins were found to be overexpressed in a previous well respected study of mouse hematopoeitic stem cells (Ramalho-Santos et al, Science2002;298(5593)). To further validate these findings, we performed gene expression array analysis on primary bone marrow cells using a completely different platform (Nimblegen 37K arrays) and demonstrated enrichment of majority of these genes. Thus, we provide a blueprint for conducting similar meta-analysis across various microarray platforms and our findings disclose tremendous platform and lab dependant differences in microarray gene expression patterns. In spite of this variability, data mining of discrete datasets can be a useful tool for gene discovery. Finally, we are in the process of constructing a publicly searchable database of normal human bone marrow gene expression which may serve as a source of controls for gene expression studies of hematopoeitic malignancies by various investigators.

A Human Lymphoid Progenitor Capable of Circulating and Seeding the Thymus.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2216-2216
Author(s):  
Emmanuelle M. Six ◽  
Delphine Bonhomme ◽  
Marta Monteiro ◽  
Kheira Beldjord ◽  
Alexandrine Garrigue ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
T Cell ◽  
T Cell Development ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Rt Pcr ◽  
Pcr Assay ◽  
First Time

Abstract Identification of a thymus-seeding progenitor originating from human bone marrow constitutes a key milestone in understanding and correcting defects in T-cell development. Here, we report the characterization of a novel human bone marrow lymphoid-restricted subpopulation which is part of the lineage-negative CD34+CD10+ progenitor population and which can be distinguished from B-cell-committed precursors by the absence of CD24 expression. We demonstrated that these Lin-CD34+CD10+CD24- progenitors lack myeloid and erythroid potential but can generate B, T and NK lymphocytes following culture on MS5 or OP9-hDelta1 stroma. The gene expression profile of this population, analyzed by a multiplex RT-PCR assay, revealed co-expression of RAG1, TdT, PAX5, CD3ε and IL-7Rα. These progenitors are not only present in the bone marrow but also in the blood throughout life, suggesting an ability to circulate. Moreover we showed that the Lin-CD34+CD10+CD24- cells also correspond to the most immature population of the thymus which gives rise to Lin-CD34+CD7+ T-cell precursors. Taken as a whole these findings unravel for the first time the existence of a postnatal lymphoid-restricted population which is capable of migrating from the bone marrow to the thymus.

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