Tissue stem cells, such as hematopoietic stem cells (HSCs), have great promise for regenerative medicine. Establishment and maintenance of the hematopoietic system relies on self-renewing HSCs. Genetic studies have identified a number of transcription factors and signaling molecules that control HSC self-renewal, and have delineated the underlying molecular mechanisms. One molecule that has been a particularly useful marker of HSC is Ecotropic viral integration site 1 (Evi1). Evi1 is a transcription factor of the SET/PR domain protein family, and is essential for the maintenance of HSC. Evi1 is notorious for its involvement in leukemia, as Evi1 activation confers the worst prognosis in patients with acute myeloid leukemia. A recent study using Evi1-green fluorescent protein reporter mice demonstrated that in vivo repopulating HSCs are exclusively enriched within the Evi1-expressing fraction in both fetal and adult hematopoietic system. Consistent with predominant expression of Evi1 in HSCs, heterozygous knockout of the Evi1 gene leads to a marked reduction of long-term HSCs with defect of their self-renewal capacity. Here we will summarize the current knowledge regarding the role of Evi1 in hematopoiesis and focus on the specific relationship between Evi1 expression and HSC self-renewal activity.

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It is now widely accept that stem cell-like cancer cells, also known as cancer initiating cells (CIC), cancer stem cells or cancer propagating cells, in various types of cancers, including malignant glioma. Because it is likely that CICs proliferate indefinitely, express characteristics of tissue-specific stem cells exist, form tumor and are resistant to chemo- and radio-therapy, it is important to establish their purification methods, characterize them and find therapeutic ways. In this review, I will summarize recent progress about glioma initiating cell that is one of best CIC models.

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The potency of specific transcription factors as cell fate determinants was first demonstrated by the discovery of MyoD, a master gene for skeletal muscle differentiation, and by the subsequent identification of several genes as lineage-converting factors within the blood cell lineage. These pioneer works led to the landmark study by Dr. Yamanaka and colleagues that is reprogramming of somatic cells into a pluripotent state by transduction of the four stem cell-specific transcription factors, Oct4, Sox2, Klf4, and c-Myc. This study fundamentally altered the approach to regenerative medicine and also inspired a new strategy to generate desired cell types by introducing combinations of lineage-specific transcription factors. In fact, it has been demonstrated that a diverse range of cell types, such as pancreatic β-cells, neurons, chondrocytes, and hepatocytes, can be induced from differentiated somatic cells using lineage specific-reprogramming factors. We and other reported that functional cardiomyocytes can be generated directly from fibroblasts using several combinations of cardiac-enriched factors in vitro and in vivo. The present article reviews the pioneering and recent studies in cellular reprogramming, and discusses the perspectives and challenges of direct cardiac reprogramming in regenerative therapy.

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The sequence of DNA is the same in all somatic cells of an organism, despite the variety of cells that exist within the organism. Mammalian blood, for example, contains a number of distinct mature cell types. These mature cells are all derived from hematopoietic stem cells (HSCs). Both HSCs and mature cells have the same genome, but their gene expression is controlled by epigenetic mechanisms such as DNA methylation and histone modification, enabling each cell-type to acquire various forms and functions. Recently, improvements in NGS (next-generation sequencing) technology have allowed extensive epigenetic analysis with small amounts of cells, improving our understanding of the role of epigenetics in stem cells. In this review, we focus on the epigenetic regulation of HSCs.

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Hypoxia is a common feature of highly proliferating tissues and tissues with inflammation. The transcriptional response to hypoxia involves activation of signal transduction pathways, which is mainly mediated by post-translational modifications of signaling molecules, transcription factors and histones. Activation of hypoxia responsive transcription factors HIF and NF-κB is a subject of regulation by reversible phosphorylation and acetylation. Moreover, hypoxia affects the balance between protein tyrosine kinases and protein tyrosine phosphatases as well as mitogen-activated protein kinases (MAPK) and mitogen activated kinase phosphatases (MKPs). Activity of both histone acetyltransferases and histone deacetylases and their association with transcription factors is specifically regulated in hypoxic and ischemic conditions. Hypoxic and cancerous switch from mitochondrial oxidative phosphorylation to glycolitic metabolism is regulated by acetylation of enzymes participating in maintaining cellular energy metabolism. This review discusses the current research implicating the regulation of protein post-translational modifications in hypoxic environment. Among the diversity of protein modifications, the regulation of acetylation and phosphorylation will be described in detail with emphasis on how these modifications affect dynamic control of cellular signaling in hypoxia-related physiological responses and pathologies. Finally, the potential of targeting post-translational modifications as therapeutic approach in the treatment of hypoxia-related disorders will be discussed in the conclusion.

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Mesenchymal stem cells (MSCs) are adult totipotent cells that can differentiate into osteoblasts and chondrocytes. Based on this property, they are theoretically useful for treatment of bone erosive diseases such as rheumatoid arthritis (RA) including joint repair. MSCs constitutively produce a variety of cytokines and growth factors, which explain their immunomodulatory effects on inflammatory cells. Recent clinical trials have shown their efficacy in graft versus host disease. However, whether MSCs can be used for treatment of RA remains unclear. Especially, there is a need to identify and characterize all soluble mediators, i.e., the “trophic effects” of MSCs on the differentiation of osteoclasts, which are involved in bone destruction in RA. We reported previously that human MSCs suppress osteoclast differentiation by constitutive production of osteoprotegerin, the decoy receptor of RANKL. Our results further highlighted the potential usefulness of MSCs for RA treatment by preventing the progression of bone damage by inhibiting osteoclast differentiation. The next step in the clinical application of MSCs includes identifying the best tissue source for these cells and refinement of RA treatment methodology. Recent studies have confirmed that MSCs are important for both bone and synovial tissue homeostasis acting as precursors of osteoblasts and chondrocytes and through their trophic effects. Taken together, MSCs are a hopeful tool to combat joint inflammation and enhance joint repair in RA, ensuring complete cure of this devastating disease.

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The clinical features of dermatomyositis (DM) have a close relationship with myositis-specific antibodies. Clinically amyopathic dermatomyositis (CADM) is a subgroup of DM, which manifests as characteristic skin symptoms compatible with DM, such as Gottron's sign and heliotrope rash with no or mild muscle symptoms. Sometimes, a life-threatening rapidly progressing interstitial lung disease can complicate CADM. In recent years, anti-CADM-140/MDA5 antibodies have been observed in serum obtained from patients with CADM. Thus, measurement of anti-CADM-140/MDA5 antibodies is useful for the diagnosis and prediction of prognosis of patients with CADM.

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