Isolation of hematopoietic stem cells and the effect of CD38 expression during the early erythroid progenitor cell development process

Albeniz, Işıl; Türker-Şener, Leyla; Baş, Aycan; Kalelioğlu, İbrahim; Nurten, Rüstem

doi:10.3892/ol.2011.455

Cited by 12 publications

(12 citation statements)

References 26 publications

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“…In our study, when examining EPO and renin levels that were decreased in Group I/R, EPO level did not show any significant change, but renin level was significantly increased especially in the groups treated with 8‐Br‐cADPR. Previous studies have reported that there was a positive correlation between CD38 and EPO, and that this contributed to progenitor cell formation (Albeniz, Turker‐Sener, Bas, Kalelioglu, & Nurten, ; Todosenko et al, ). Xiong et al () reported that the CD38/cADPR signaling pathway may contribute to the regulation of renin release.…”

Section: Discussionmentioning

confidence: 90%

8‐Br‐cADPR, a TRPM2 ion channel antagonist, inhibits renal ischemia–reperfusion injury

Eraslan

Tanyeli

Polat

2018

Journal Cellular Physiology

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The transient receptor potential melastatin-2 (TRPM2) channel belongs to the transient receptor potential channel superfamily and is a cation channel permeable to Na and Ca . The TRPM2 ion channel is expressed in the kidney and can be activated by various molecules such as hydrogen peroxide, calcium, and cyclic adenosine diphosphate (ADP)-ribose (cADPR) that are produced during acute kidney injury. In this study, we investigated the role of 8-bromo-cyclic ADP-ribose (8-Br-cADPR; a cADPR antagonist) in renal ischemia-reperfusion injury using biochemical and histopathological parameters. CD38, cADPR, tumor necrosis factor-α, interleukin-1β, and myeloperoxidase (inflammatory markers), urea and creatinine, hydrogen peroxide (oxidant), and catalase (antioxidant enzyme) levels that increase with ischemia-reperfusion injury decreased in the groups treated with 8-Br-cADPR. In addition, renin levels were elevated in the groups treated with 8-Br-cADPR. Histopathological examination revealed that 8-Br-cADPR reduced renal damage and the expression of caspase-3 and TRPM2. Our results suggest that the inhibition of TRPM2 ion channel may be a new treatment modality for ischemic acute kidney injury.

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Section: Discussionmentioning

confidence: 90%

8‐Br‐cADPR, a TRPM2 ion channel antagonist, inhibits renal ischemia–reperfusion injury

Eraslan

Tanyeli

Polat

2018

Journal Cellular Physiology

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“…CD38 is a type II membrane surface glycoprotein expressed on a variety of mature hematopoietic cells. CD38 expression is either low or absent on early HSPC populations and most definitions of the primitive, pluripotent human HSCs are contained within the CD34 + /CD38 − fraction . CD34 + /CD38 − cells comprise only ∼1%–3% of CD34 + cells and thus are 50–100 times more enriched for HSPC than the unfractionated CD34 + population.…”

Section: Introductionmentioning

confidence: 99%

Enrichment of Human Hematopoietic Stem/Progenitor Cells Facilitates Transduction for Stem Cell Gene Therapy

et al. 2015

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Autologous hematopoietic stem cell (HSC) gene therapy for sickle cell disease has the potential to treat this illness without the major immunological complications associated with allogeneic transplantation. However, transduction efficiency by β-globin lentiviral vectors using CD34-enriched cell populations is suboptimal and large vector production batches may be needed for clinical trials. Transducing a cell population more enriched for HSC could greatly reduce vector needs and, potentially, increase transduction efficiency. CD34+/CD38− cells, comprising ~1%–3% of all CD34+ cells, were isolated from healthy cord blood CD34+ cells by fluorescence-activated cell sorting and transduced with a lentiviral vector expressing an antisickling form of beta-globin (CCL-βAS3-FB). Isolated CD34+/CD38− cells were able to generate progeny over an extended period of long-term culture (LTC) compared to the CD34+ cells and required up to 40-fold less vector for transduction compared to bulk CD34+ preparations containing an equivalent number of CD34+/CD38− cells. Transduction of isolated CD34+/CD38− cells was comparable to CD34+ cells measured by quantitative PCR at day 14 with reduced vector needs, and average vector copy/cell remained higher over time for LTC initiated from CD34+/38− cells. Following in vitro erythroid differentiation, HBBAS3 mRNA expression was similar in cultures derived from CD34+/CD38− cells or unfractionated CD34+ cells. In vivo studies showed equivalent engraftment of transduced CD34+/CD38− cells when transplanted in competition with 100-fold more CD34+/CD38+ cells. This work provides initial evidence for the beneficial effects from isolating human CD34+/CD38− cells to use significantly less vector and potentially improve transduction for HSC gene therapy.

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“…The change in CD38 expression was ranked as the second-most significant change and CD93 as the twelfth-most significant change by differential gene expression analysis with DEseq [98]. Interestingly, the CD38 and CD93 expression levels are important biomarkers for leukemia cell immunophenotype: CD34 + CD38 − cells are a primitive sub-population of progenitor cells which are generally highly quiescent [107], while the cell surface lectin CD93 is expressed on a sub-population of these cells, identifying them as predominantly cycling, non-quiescent leukemia-initiating cells [108]. Therefore, the changes in CD38 and CD93 RNA expression exhibited by molm-13 R2 cells are consistent with a phenotypic shift toward a more stem-like quiescent cell.…”

Section: Discussionmentioning

confidence: 99%

A mean-field approach for modeling the propagation of perturbations in biochemical reaction networks

Przedborski

Sharon

Chan

et al. 2021

Preprint

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Often, the time evolution of a biochemical reaction network is crucial for determining the effects of combining multiple pharmaceuticals. Here we illustrate a mathematical framework for modeling the dominant temporal behaviour of a complicated molecular pathway or biochemical reaction network in response to an arbitrary perturbation, such as resulting from the administration of a therapeutic agent. The method enables the determination of the temporal evolution of a target protein as the perturbation propagates through its regulatory network. The mathematical approach is particularly useful when the experimental data that is available for characterizing or parameterizing the regulatory network is limited or incomplete. To illustrate the method, we consider the examples of the regulatory networks for the target proteins c-Myc and Chop, which play an important role in venetoclax resistance in acute myeloid leukemia. First we show how the networks that regulate each target protein can be reduced to a mean-field model by identifying the distinct effects that groups of proteins in the regulatory network have on the target protein. Then we show how limited proteinlevel data can be used to further simplify the mean-field model to pinpoint the dominant effects of the network perturbation on the target protein. This enables a further reduction in the number of parameters in the model. The result is an ordinary differential equation model that captures the temporal evolution of the expression of a target protein when one or more proteins in its regulatory network have been perturbed. Finally, we show how the dominant effects predicted by the mathematical model agree with RNA sequencing data for the regulatory proteins comprising the molecular network, despite the model not having a priori knowledge of this data. Thus, while the approach gives a simplified model for the expression of the target protein, it allows for the interpretation of the effects of the perturbation on the regulatory network itself. This method can be easily extended to sets of target proteins to model components of a larger systems biology model, and provides an approach for partially integrating RNA sequencing data and protein expression data. Moreover, it is a general approach that can be used to study drug effects on specific protein(s) in any disease or condition.

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Isolation of hematopoietic stem cells and the effect of CD38 expression during the early erythroid progenitor cell development process

Cited by 12 publications

References 26 publications

8‐Br‐cADPR, a TRPM2 ion channel antagonist, inhibits renal ischemia–reperfusion injury

8‐Br‐cADPR, a TRPM2 ion channel antagonist, inhibits renal ischemia–reperfusion injury

Enrichment of Human Hematopoietic Stem/Progenitor Cells Facilitates Transduction for Stem Cell Gene Therapy

A mean-field approach for modeling the propagation of perturbations in biochemical reaction networks

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