transfected cells was associated with down-regulation of TRP ion channel expression. Finally, we demonstrated that TGF-b/SMAD signaling augments the development of MKs derived from CB-CD34 +. Present data suggest that RUNX1/TGF-b pathway cross talk is crucial for MK maturation.
Hematopoiesis is the process which generates all the mature blood cells from the rare pool of Hematopoietic stem cells (HSCs). Asymmetric cell division of HSCs provide it dual capacity for self-renewal and multi-potent differentiation. Hematopoiesis is a steady state process in which mature blood cells are produced at the same rate at which they are lost, establishing a homeostasis. HSCs are regulated through their environmental niche, cytokine signalling, and the orchestrated activities of various transcription factors. However, there is very little information available about the signal transduction events that regulate HSC function; in particular, the effects of bioactive lipids and lipid mediators are not well understood. Recent studies have added an important aspect of this process, introducing the role of lipids in cell fate decisions during hematopoiesis. The mechanisms of bioactive lipids and their derivatives have been studied extensively in signal transduction and various other cellular processes. This review focuses on various categories of lipids and their regulatory mechanisms in HSCs and their comment into different blood cells. Moreover, we also discuss the role of lipid signalling specifically in megakaryocyte and platelets.
Major breakthroughs in the last several decades have contributed to our knowledge of the genetic regulation in development. Although epigenetics is not a new concept, unfortunately, the role of epigenetics has not come to fruition in the past. But the field of epigenetics has exploded within the past decade. Now, growing evidences show a complex network of epigenetic regulation in development. The epigenetic makeup of a cell, tissue or individual is much more complex than their genetic complement. Epigenetic modifications are more important for normal development by maintaining the gene expression pattern in tissue- and context-specific manner. Deregulation of epigenetic mechanism can lead to altered gene expression and its function, which result in altered tissue specific function of cells and malignant transformation. Epigenetic modifications directly shape Hematopoietic Stem Cell (HSC) developmental cascades, including their maintenance of self-renewal and multilineage potential, lineage commitment, and aging. Hence, there is a growing admiration for epigenetic players and their regulatory function in haematopoiesis. Epigenetic mechanisms underlying these modifications in mammalian genome are still not completely understood. This review mainly explains 3 key epigenetics mechanisms including DNA methylation, histone modifications and non-coding RNAs inference in hematopoietic lineage commitment and differentiation.
Endocannabinoids are well-known regulators of neurotransmission by activating the cannabinoid (CB) receptors. Endocannabinoids are being used extensively for the treatment of various neurological disorders such as Alzheimer's and Parkinson's diseases. Although endocannabinoids are well studied in cell survival, proliferation, and differentiation in various neurological disorders and several cancers, the functional role in the regulation of blood cell development is less examined. In the present study, virodhamine, which is an agonist of CB receptor-2, was used to examine its effect on megakaryocytic development from a megakaryoblastic cell. We observed that virodhamine increases cell adherence, cell size, and cytoplasmic protrusions. Interestingly, we have also observed large nucleus and increased expression of megakaryocytic marker (CD61), which are the typical hallmarks of megakaryocytic differentiation. Furthermore, the increased expression of CB2 receptor was noticed in virodhamine-induced megakaryocytic cells. The effect of virodhamine on megakaryocytic differentiation could be mediated through CB2 receptor. Therefore, we have studied virodhamine induced molecular regulation of megakaryocytic differentiation; mitogen-activated protein kinase (MAPK) activity, mitochondrial function, and reactive oxygen species (ROS) production were majorly affected. The altered mitochondrial functions and ROS production is the crucial event associated with megakaryocytic differentiation and maturation. In the present study, we report that virodhamine induces megakaryocytic differentiation by triggering MAPK signaling and ROS production either through MAPK effects on ROS-generating enzymes or by the target vanilloid receptor 1-mediated regulation of mitochondrial function.
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