MicroRNAs are shaping the hematopoietic landscape

Miltenyi Biotec GmbH, Bergisch Gladbach, Germany.
Haematologica (Impact Factor: 5.81). 11/2011; 97(2):160-7. DOI: 10.3324/haematol.2011.051730
Source: PubMed


Hematopoiesis is regulated by microRNAs (miRNAs). These small regulatory RNAs are master regulators of developmental processes that modulate expression of several target genes post-transcriptionally. Various miRNAs are up-regulated at specific stages during hematopoietic development and the functional relevance of miRNAs has been proven at many different stages of lineage specification. Knockout of specific miRNAs can produce dramatic phenotypes leading to severe hematopoietic defects. Furthermore, several studies demonstrated that specific miRNAs are differentially expressed in hematopoietic stem cells. However, the emerging picture is extremely complex due to differences between species, cell type dependent variation in miRNA expression and differential expression of diverse target genes that are involved in various regulatory networks. There is also evidence that miRNAs play a role in cellular aging or in the inter-cellular crosstalk between hematopoietic cells and their microenvironment. The field is rapidly evolving due to new profiling tools and deep sequencing technology. The expression profiles of miRNAs are of diagnostic relevance for classification of different diseases. Recent reports on the generation of induced pluripotent stem cells with miRNAs have fuelled the hope that specific miRNAs and culture conditions facilitate directed differentiation or culture expansion of the hematopoietic stem cell pool. This review summarizes our current knowledge about miRNA expression in hematopoietic stem and progenitor cells, and their role in the hematopoietic stem cell niche.

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Available from: Wolfgang Wagner, Jun 06, 2014
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    • "MicroRNAs (miRNAs) have been found to circulate in serum and their expression levels vary in physiological and pathological conditions [2] [3]. Furthermore, they are important regulators of cell fate and are able to influence hematopoietic stem cell proliferation and differentiation [4]. In this study [5], we have compared the miRNA expression profiles of serum from nine patients with lymphoma, acute myeloid leukemia (AML) or multiple myeloma (MM) before and after therapy as well as seven healthy donors as control. "
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    Genomics Data 09/2015; 6. DOI:10.1016/j.gdata.2015.08.018
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    • "The process of hematopoiesis involves HSCs self-renewal and lineage commitment procedures which are regulated by extrinsic factors (bone marrow microenvironment, cell adhesion molecules, growth factors and cytokines ) (Zhu and Emerson, 2002) and intrinsic factors (signalling networks and transcription factors) (Akala and Clarke, 2006). miRNAs is known as a novel regulatory molecules in hematopoiesis by targeting intrinsic factors involved in hematopoiesis, can effect on HSCs expansion, maintaining selfrenewal , differentiation, apoptosis and other biology processes (Bissels et al., 2012; Favreau and Sathyanarayana, 2012). Recently , deregulation of miRNAs has been shown in leukemia that is linked to breakpoint regions associated with chromosome aberrations in leukemias (Zimmerman and Wu, 2011). "
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    ABSTRACT: Hematopoietic Stem Cells (HSCs) are cells that have the ability to self-renewal and differentiate into all of hematopoietic lineages. The lack of donors and unavailable efficient protocols for ex vivo expansion of HSCs, are obstacles in successful cell therapies. MicroRNAs (also refer as miRNAs or miRs) have significant roles in hematopoiesis; they can effect on HSCs expansion, maintaining undifferentiated state, self-renewal and differentiation. Recently attentions have been given to these small regulatory molecules to utilize them in order to expand HSCs. Using bioinformatics analysis we identified Sall4 as putative target of miR-15b and miR-219-5p. Relative expression levels of miRNAs and Sall4 were evaluated by qRT-PCR. Here we show 247-fold and 4.2fold increasing Sall4 expression level compared to control group in CD34+ cells nucleofected by anti-miR-15b and anti-miR-219-5p, respectively. These data showed that anti-miR-15b can promote clonogenic capacity of HSCs and also we found that miR-15b alone was able to increase the number of CD34+HSCs in vitro by more than 2 fold by targeting Sall4. Moreover, level of CD34 marker in HSCs nucleofected by anti-miR-15b increased more than 50%. Our analysis showed no statistically difference in mRNA level of Sall4 after nucleofection of anti-miR-219-5p. Sall4 is a factor capable of enhancing HSC expansion significantly. We demonstrated that inhibition of miR-15b can enhance ex vivo expansion of UCB-derived HSCs and also expression of Sall4 allowed expansion and preserve self- renewal of CD34+ HSCs. © 2015, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved.
    EXCLI Journal 05/2015; 14:601-610. DOI:10.17179/excli2014-687 · 0.86 Impact Factor
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    • "As BM stromal cells, MSCs play an important role in the production of CXCL12. Evidence suggests that miRNAs are regulatory molecules in the inter-cellular crosstalk between these cells and the microenvironment of BM (Bissels et al. 2012; Saki et al. 2011). Since CXCL12 is an important factor in transendothelial migration stimulating the motility of tumor cells, controlling the expression of this chemokine by certain miRNAs, such as miR-27b, miR-146a- 5p and miR-886-3p, can reduce the metastatic potential of cancer cells (Clark et al. 2014; Shi et al. 2014). "
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    ABSTRACT: Chemokines secreted from different cellular components of bone marrow (BM) play an important role in the formation of the BM niche system. The hematopoietic stem cell (HSC) pool located in specialized anatomical sites within the BM is subjected to a complex network of chemokines, such that the produced chemokines affect the fate of these cells. Expression of different chemokine receptors on leukemic stem cells (LSCs) uncovers the critical role of chemokines in the maintenance, survival and fate of these cells in the leukemic niche. As a pre-metastatic niche rich in a variety of chemokines, the BM niche is turned into a locus of tumor cell development and division. The chemokine receptors expressed on the surface of metastatic cells lead to their metastasis and homing to the BM niche. Knowledge of chemokines and their receptors leads to the production of various therapeutic antagonists at chemokine receptors expressed on leukemic and tumor cells, enabling interference with chemokine function as a therapeutic tool. New findings suggest that miRNAs, with their specific inhibitory function, affect the ability of producing and expressing chemokines and chemokine receptors. This review focuses on the emerging role of chemokines and their receptors in normal and pathologic conditions of the BM niche, and also discusses the new therapeutic methods with this background.
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