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Parsing the niche code: The molecular mechanisms governing hematopoietic stem cell adhesion and differentiation

Haematologica (Impact Factor: 5.87). 11/2009; 94(11):1477-81. DOI: 10.3324/haematol.2009.013730
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    • "They are endowed with multilineage differentiation potential toward mesodermal cell lineages and extensive immunomodulatory properties. MSCs actively proliferate in some tissues, but remain quiescent in others [29]. Three main criteria have been identified by the International Society of Cellular Therapy to define MSCs: (i) adhesion to plastic, (ii) expression of specific immunophenotypic marker combinations (CD73, CD90, and CD105), accompanied by lack of expression of hematopoietic markers (CD14, CD34, and CD45) and class II major histocompatibility complex (MHC) molecules; (iii) capability of differentiating into mesodermal lineages (adipocytes, cardiomyocytes, osteoblasts, and chondrocytes) [30] [31]. "
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    ABSTRACT: Hematopoietic stem cells (HSCs) reside in bone marrow niches and give rise to hematopoietic precursor cells (HPCs). These have more restricted lineage potential and eventually differentiate into specific blood cell types. Bone marrow also contains mesenchymal stromal cells (MSCs), which present multilineage differentiation potential toward mesodermal cell types. In bone marrow niches, stem cell interaction with the extracellular matrix is mediated by integrin receptors. Ion channels regulate cell proliferation and differentiation by controlling intracellular Ca(2+), cell volume, release of growth factors, and so forth. Although little evidence is available about the ion channel roles in true HSCs, increasing information is available about HPCs and MSCs, which present a complex pattern of K(+) channel expression. K(+) channels cooperate with Ca(2+) and Cl(-) channels in regulating calcium entry and cell volume during mitosis. Other K(+) channels modulate the integrin-dependent interaction between leukemic progenitor cells and the niche stroma. These channels can also regulate leukemia cell interaction with MSCs, which also involves integrin receptors and affects the MSC-mediated protection from chemotherapy. Ligand-gated channels are also implicated in these processes. Nicotinic acetylcholine receptors regulate cell proliferation and migration in HSCs and MSCs and may be implicated in the harmful effects of smoking.
    08/2012; 2012(1687-966X):217910. DOI:10.1155/2012/217910
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    • "Other factors also contribute to HSC localization to the BM either in conjunction with CXCR4, such as prostaglandin E2 (PGE2) and the neuronal guidance protein Robo4 (Hoggatt et al., 2009; Smith-Berdan et al., 2011), or independently from CXCR4 like c-Kit, the calcium-sensing receptor (CaR), and the transcription factor Egr1 (Christensen et al., 2004; Adams et al., 2006; Min et al., 2008). Thereafter, HSCs remain anchored in the BM niche by complex integrindependent mechanisms (Scott et al., 2003; Forsberg and Smith- Berdan 2009), though small numbers of HSCs will periodically migrate from the BM into the circulation and back for short periods of time under homeostatic conditions, perhaps as a form of immunosurveillance (Massberg et al., 2007; Bhattacharya et al., 2009). Taken together, these data underscore the dynamic nature of hematopoietic development from embryogenesis through adulthood. "
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    ABSTRACT: Hematopoietic stem cells (HSCs) give rise to all lineages of blood cells. Because HSCs must persist for a lifetime, the balance between their proliferation and quiescence is carefully regulated to ensure blood homeostasis while limiting cellular damage. Cell cycle regulation therefore plays a critical role in controlling HSC function during both fetal life and in the adult. The cell cycle activity of HSCs is carefully modulated by a complex interplay between cell-intrinsic mechanisms and cell-extrinsic factors produced by the microenvironment. This fine-tuned regulatory network may become altered with age, leading to aberrant HSC cell cycle regulation, degraded HSC function, and hematological malignancy.
    The Journal of Cell Biology 11/2011; 195(5):709-20. DOI:10.1083/jcb.201102131 · 9.69 Impact Factor
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    ABSTRACT: The production of blood and immune cells is a continuous process throughout life and essential for the existence of any individual human being. This process is referred to as HEMATOPOIESIS (from the Greek hematos, blood, and poiein, to generate) and includes the generation of ERYTHROCYTES (red cells), THROMBOCYTES (platelets) and LEUKOCYTES (white blood cells, consisting of various types of GRANULOCYTES, LYMPHOCYTES and MONOCYTES). The major site of HEMATOPOIESIS is the BONE MARROW, but it can occur at other (extramedullary) locations as well.
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