Gene expression profiling in CD34 cells to identify differences between aplastic anemia patients and healthy volunteers

Zhang, Weihua; Chen, Guibin; Kajigaya, Sachiko; Núñez, Olga; Charrow, Alexandra; Billings, Eric M.; Young, Neal S.

doi:10.1182/blood-2003-02-0490

Cited by 88 publications

(71 citation statements)

References 38 publications

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“…Previously, we demonstrated decreased expression of GATA-2 in CD34-positive cells in AA (Fujimaki et al 2001). This observation was confirmed in another study utilizing microarray-based transcriptional profiling of CD34-positive cells from patients with AA (Zeng et al 2004). Furthermore, the merged analysis of GATA-2 ChIP-seq and expression profiling identified HOXB4, which encodes a protein with an important role in HSC expansion (Antonchuk et al 2002), as a direct downstream target (Fujiwara et al 2009).…”

Section: Human Diseases Caused By Gata-2 Dysregulationmentioning

confidence: 49%

GATA Transcription Factors: Basic Principles and Related Human Disorders

Fujiwara

2017

Tohoku J. Exp. Med.

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Section: Human Diseases Caused By Gata-2 Dysregulationmentioning

confidence: 49%

GATA Transcription Factors: Basic Principles and Related Human Disorders

Fujiwara

2017

Tohoku J. Exp. Med.

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“…190 This important observation indicates that in aplastic anemia, CD34 þ cells represent the main target of an immunologically mediated damage.…”

Section: Apoptotic Mechanisms In Aplastic Anemiamentioning

confidence: 99%

Apoptotic mechanisms in the control of erythropoiesis

2004

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Erythropoiesis is a complex multistep process encompassing the differentiation of hemopoietic stem cells to mature erythrocytes. The steps involved in this complex differentiation process are numerous and involve first the differentiation to early erythoid progenitors (burst-forming units-erythroid, BFU-E), then to late erythroid progenitors (colony-forming unitserythroid) and finally to morphologically recognizable erythroid precursors. A key event of late stages of erythropoiesis is nuclear condensation, followed by extrusion of the nucleus to produce enucleated reticulocytes and finally mature erythrocytes. During the differentiation process, the cells became progressively sensitive to erythropoietin that controls both the survival and proliferation of erythroid cells.A normal homeostasis of the erythropoietic system requires an appropriate balance between the rate of erythroid cell production and red blood cell destruction. Growing evidences outlined in the present review indicate that apoptotic mechanism play a relevant role in the control of erythropoiesis under physiologic and pathologic conditions. Withdrawal of erythropoietin or stimulation of death receptors such as Fas or TRAIL-Rs leads to activation of a subset of caspases-3, -7 and -8, which then cleave the transcription factors GATA-1 and TAL-1 and trigger apoptosis. In addition, there is evidence that a number of caspases are physiologically activated during erythroid differentiation and are functionally required for erythroid maturation. Several caspase substrates are cleaved in differentiating cells, including the protein acinus whose activation by cleavage is required for chromatin condensation.The studies on normal erythropoiesis have clearly indicated that immature erythroid precursors are sensitive to apoptotic triggering mediated by activation of the intrinsic and extrinsic apoptotic pathways. These apoptotic mechanisms are frequently exacerbated in some pathologic conditions, associated with the development of anemia (ie, thalassemias, multiple myeloma, myelodysplasia, aplastic anemia).The considerable progress in our understanding of the apoptotic mechanisms underlying normal and pathologic erythropoiesis may offer the way to improve the treatment of several pathologic conditions associated with the development of anemia.

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“…We have also demonstrated that GATA2 expression in HSC is lower in patients with aplastic anemia and leads to decreased HOXB4 expression, 19,20 which would contribute to the reduction in the size of the HSC pool. 26 Furthermore, GATA2 expression is also lower in BM-MSC derived from patients with aplastic anemia.…”

Section: Regulation Of Bm-msc Differentiation By Gata2mentioning

confidence: 99%

“…19,20 Because cytokines such as transforming growth factor-β, 37 interferon-γ, 37 tumor necrosis factor-α, 38,39 IL-6, 39 IL-17A, 39 and IL-1β 40,41 may be involved in the pathogenesis of aplastic anemia, we evaluated whether the addition of these cytokines may accelerate adipocyte differentiation. Unexpectedly, adipocyte differentiation was suppressed by these cytokines, except for IL-6 (Online Supplementary Figure S5A-F).…”

Section: Regulation Of Bm-msc Differentiation By Gata2mentioning

confidence: 99%

“…Moreover, GATA2 expression is decreased in CD34-positive cells in aplastic anemia, 19,20 Because BM-MSC express GATA2, it is possible that the signal that downregulates GATA2 expression in HSC may also suppress its expression in BM-MSC in aplastic anemia, thereby resulting in fewer HSC and an impaired microenvironment, which could support hematopoiesis. To test this hypothesis, we assessed the role of GATA2 during differentiation from BM-MSC.…”

Section: Introductionmentioning

confidence: 99%

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GATA2 regulates differentiation of bone marrow-derived mesenchymal stem cells

et al. 2014

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Methods Generation of bone marrow mesenchymal stem cellsTo generate mouse BM-MSC, bone marrow cells from GATA2 conditional knockout mice were cultured in MesenCult MSC Basal Medium supplemented with 20% MSC stimulatory supplements (Stem Cell Technologies). The BM-MSC were transfected with the retroviruses expressing iCre to delete the DNA binding domain of GATA2 by inducing the Cre-loxP system. 21,22 To generate human BM-MSC, bone marrow mononuclear cells from healthy donors were cultured with Dulbecco's modified Eagle's medium (Life Technologies) supplemented with 20% fetal bovine serum (Life Technologies), 10 ng/mL basic fibroblast growth factor (PeproTech), 10 mM HEPES (Life Technologies), and 100 μg/mL penicillin/streptomycin (Invitrogen). [23][24][25] Established BM-MSC were used until the seventh generation.The study was approved by the ethical committee of Tohoku University Graduate School of Medicine. Clinical samples were collected after obtaining written informed consent. The ethics policies of the Declaration of Helsinki were followed. Characterization of bone marrow mesenchymal stem cellsBM-MSC immunophenotypes were determined using a FACSAria II (BD). To induce differentiation into adipocytes, human Mesenchymal Stem Cell Adipogenic Differentiation Medium (Lonza) was used. After 12-16 days, morphological changes were assessed using an inverted microscope. Typical adipocytes were stained with Oil Red O.2 The area of mature adipocytes was determined using HistoQuest software (Novel Science). Quantitative reverse transcriptase polymerase chain reaction analysis and transcription profilingQuantitative reverse transcriptase polymerase chain reaction analysis (RT-PCR) was performed as previously described.26 Primer sequences are available upon request.For transcription profiling, the Human Genome U133 Plus 2.0 Array was used (Affymetrix). Gene ontology analysis was conducted using the DAVID bioinformatics program (http://david.abcc.ncifcrf.gov/). Short interfering RNA-mediated knockdownAnti-GATA2 and control short interfering RNA (siRNA) 26 were transfected into human BM-MSC with Lipofectamine TM RNAiMAX reagent (Life Technologies). Cells were analyzed 48 h after transfection. Viral vectors and cell transductionRetroviral overexpression of GATA2 was performed using the MSCV retrovirus vector, which co-expresses green fluorescent protein (GFP) by internal ribosome entry sites (IRES), transfecting into Platinum Retroviral Packaging Cell Lines (PLAT-F) 27 with FuGENE HD (Roche). Human BM-MSC were pretreated with Retronectin (TAKARA BIO.), and GFP-positive cells were sorted using FACSAria II (BD Biosciences).Co-culture of CD34-positive-enriched cells with a mesenchymal stem cell feeder layer BM-MSC were transfected with control or GATA2-siRNA. On day 3, control and GATA2 knockdowned BM-MSC, respectively, were replaced with serum-free medium containing CD34-positiveenriched cells (RIKEN). Serum-free medium (StemPro-34 SFM: Life Technologies) contained 100 ng/mL stem cell factor, 100 ng/mL interleukin (...

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Gene expression profiling in CD34 cells to identify differences between aplastic anemia patients and healthy volunteers

Cited by 88 publications

References 38 publications

GATA Transcription Factors: Basic Principles and Related Human Disorders

GATA Transcription Factors: Basic Principles and Related Human Disorders

Apoptotic mechanisms in the control of erythropoiesis

GATA2 regulates differentiation of bone marrow-derived mesenchymal stem cells

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