Transcriptomics

Dataset Information

5

Gene expression and epigenetic profiling of CD34+ hematopoietic progenitor cells in multiple sclerosis patients (expression)


ABSTRACT: Intense immunosuppression followed by autologous hematopoietic stem cell transplantation (aHSCT) is a potential treatment for patients suffering from aggressive multiple sclerosis (MS). However it remains unresolved whether autologous CD34+ hematopoietic progenitor cells of MS patients show gene expression differences prior to aHSCT that indicate a preset proinflammatory state, which would then also predispose to or predetermine recurrence of the autoimmune disease. To approach this key point we compared the gene expression signature of CD34+ and CD34- cells collected from MS patients and healthy donors (HD). Whole genome gene expression of CD34+ and CD34- cells was analysed with the Human 4x44K Design Array (Agilent-Technologies). As main observation we found only minor differences in the gene expression signature of MS patients compared to HD. Only a single gene, troponin-type-1 (TNNT1), reached statistical significance after correction for multiple comparisons (logFC=3.1, p<0.01). There was a decreased expression of several protease genes, myeloperoxidase (MPO), neutrophil-elastase (ELA2), cathepsin-G (CTSG) and serine-protease 21 (PRSS21) in HPCs of MS patients, albeit not reaching statistical significance. In summary we did not detect substantial alterations in the gene expression profile of CD34+ HPCs in MS. Our data support the use of autologous hematopoietic stem cell transplantation for treatment of an autoimmune disease. Samples of CD34+ cells were obtained from 4 female MS patients and 4 age matched healthy donors (3 female) mobilized by G-CSF (2x5μg/kg/day) and 4 MS patients (2 female) mobilized by G-CSF (5μg/kg/day) plus Cyclophosphamide (Cy, 4g/m2). White blood cells, containing the CD34+ cell fraction, were collected by leucocytapheresis from peripheral blood, frozen and stored in liquid nitrogen. All samples were thawed and processed at one center and CD34+ HPCs purified by magnetic bead separation using the autoMACS system (Miltenyi). Purity and viability of CD34+ cells was analyzed by Fluorescence Activated Cell Sorter (FACS). Total cellular RNA were extracted with TRIzol reagent and analyzed with the Human 4x44K Design Array (Agilent-Technologies).

ORGANISM(S): Homo sapiens  

SUBMITTER: Mireia Sospedra  Massimo DiGioia  Andreas Sputtek  Luca Massacesi  Riccardo Saccardi  Annamaria Repice  Roland Martin  Nicolaus Kroeger  Gabriela Salinas-Riester  Axel Zander 

PROVIDER: E-GEOD-27688 | ArrayExpress | 2012-09-05

SECONDARY ACCESSION(S): GSE27688PRJNA141875

REPOSITORIES: GEO, ArrayExpress

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Publications

No proinflammatory signature in CD34+ hematopoietic progenitor cells in multiple sclerosis patients.

Lutterotti A A   Jelcić I I   Schulze C C   Schippling S S   Breiden P P   Mazzanti B B   Reinhardt S S   DiGioia M M   Repice A A   Massacesi L L   Sputtek A A   Salinas-Riester G G   Kroeger N N   Sospedra M M   Saccardi R R   Zander A A   Martin R R  

Multiple sclerosis (Houndmills, Basingstoke, England) 20120117 8


Autologous hematopoietic stem cell transplantation (aHSCT) has been used as a therapeutic approach in multiple sclerosis (MS). However, it is still unclear if the immune system that emerges from autologous CD34+ hematopoietic progenitor cells (HPC) of MS patients is pre-conditioned to re-develop the proinflammatory phenotype. The objective of this article is to compare the whole genome gene and microRNA expression signature in CD34+ HPC of MS patients and healthy donors (HD). CD34+ HPC were isol  ...[more]

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