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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    ABSTRACT: Recovery of the blood and immune system after chemotherapy requires proliferation of hematopoietic stem and progenitor cells (HPSCs). It has been shown that systemically released factors in serum after chemotherapy stimulate HSPC expansion in vitro. We wondered if microRNAs (miRNAs) circulating in serum could account for this effect. Therefore, we compared the miRNA expression profiles of serum from patients with hematologic malignancies before and after chemotherapy. In addition to a general decrease in miRNA expression after chemotherapy, we found 23 miRNAs to be significantly differentially expressed in serum before versus after chemotherapy. The miRNA microarray data are available at NCBI’s Gene Expression Omnibus (GEO) Series accession number GSE57570. Here, we provide a detailed protocol of the miRNA microarray and data analysis.
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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.
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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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