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Untersuchte Arbeit:
Seite: 10, Zeilen: 1 ff.
Quelle: Smith 2003
Seite(n): Internet, Zeilen: Internet
1.2.2 Hematopoiesis

The process of hematopoiesis involves a complex interplay between the intrinsic genetic processes of blood cells and their environment. This interplay determines whether HSC, progenitors, and mature blood cells remain quiescent, proliferate, differentiate, self-renew, or undergo apoptosis.[14-16] All of the genetic and environmental mechanisms that govern blood production operate by affecting the relative balance of these fundamental cellular processes. Under normal conditions, the majority of HSC and many progenitors are quiescent in the G0 phase of the cell cycle; however, many of the more mature progenitors are proliferating and producing mature offspring [17]. In the absence of any stresses, this is balanced by the rate of apoptosis in progenitors and mature cells [15]. In the event of a stress such as bleeding or infection, several processes occur. Stored pools of cells in the marrow or adherent to the endothelium are quickly released into the circulation in order to localize to the site of injury [18]. Fewer progenitors and mature cells undergo apoptosis [19, 20]. In addition, quiescent progenitors and HSC are stimulated by a variety of growth factors to proliferate and differentiate into mature white cells, red blood cells, and platelets. When the bleeding, infection, or other underlying stress ceases and the demand for blood cells returns to normal, the antiapoptotic and proliferative processes wind down, blood cells are redistributed back to their storage sites, and the kinetics of hematopoiesis return to baseline levels. This process repeats itself innumerable times during the lifespan of an individual and is seen in an exaggerated form following chemotherapy or bone marrow transplantation.

Probably the best characterized environmental regulators of hematopoiesis are cellular microenvironment, known as niche. It functions as an extrinsic regulatory system, which maintains and governs the location, adhesiveness, retention, homing, mobilization, quiescence/activation, symmetric/asymmetric division and differentiation. [21]

Cytokines are a broad family of proteins that mediate positive and negative affects on cellular quiescence, apoptosis, proliferation, and differentiation. In general, cytokines function by engaging a specific receptor and activating a [variety of signaling pathways.]

The process of hematopoiesis involves a complex interplay between the intrinsic genetic processes of blood cells and their environment. This interplay determines whether HSCs, progenitors, and mature blood cells remain quiescent, proliferate, differentiate, self-renew, or undergo apoptosis.[30-32] All of the genetic and environmental mechanisms that govern blood production operate by affecting the relative balance of these fundamental cellular processes. Under normal conditions, the majority of HSCs and many progenitors are quiescent in the G0 phase of the cell cycle; however, many of the more mature progenitors are proliferating and producing mature offspring.[33] In the absence of any stresses, this is balanced by the rate of apoptosis in progenitors and mature cells.[31] In the event of a stress such as bleeding or infection, several processes occur. Stored pools of cells in the marrow or adherent to the endothelium are quickly released into the circulation in order to localize to the site of injury.[34] Fewer progenitors and mature cells undergo apoptosis.[35,36] In addition, quiescent progenitors and HSCs are stimulated by a variety of growth factors to proliferate and differentiate into mature white cells, red blood cells, and platelets. When the bleeding, infection, or other underlying stress ceases and the demand for blood cells returns to normal, the anti-apoptotic and proliferative processes wind down, blood cells are redistributed back to their storage sites, and the kinetics of hematopoiesis return to baseline levels. This process repeats itself innumerable times during the lifespan of an individual and is seen in an exaggerated form following chemotherapy or bone marrow transplantation.

Probably the best characterized environmental regulators of hematopoiesis are cytokines.[37] Cytokines are a broad family of proteins that mediate positive and negative affects on cellular quiescence, apoptosis, proliferation, and differentiation. In general, cytokines function by engaging a specific receptor and activating a variety of signaling pathways

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