Cytokine signalling in embryonic stem cells

Abstract

Cytokines play a central role in maintaining self-renewal in mouse embryonic stem (ES) cells through a member of the interleukin-6 type cytokine family termed leukemia inhibitory factor (LIF). LIF activates the JAK-STAT3 pathway through the class I cytokine receptor gp130, which forms a trimeric complex with LIF and the class I cytokine receptor LIF receptor b. STAT3 has been shown to play a crucial role in self-renewal in mouse ES cells probably by induction of c-myc expression. Thus, ablation of STAT3 activation leads to differentiation. However, important connections between STAT3 and other signalling pathways have been documented. In addition, gp130 activation leads to both PI3K and Src activation. The canonical Wnt pathway is sufficient to maintain self-renewal of both human ES cells and mouse ES cells. It seems quite possible that the main pathway maintaining self-renewal in ES cells is the Wnt pathway, while the LIF-JAK-STAT3 pathway is present in mouse cells as an adaptation for sustaining self-renewal during embryonic diapause, a condition of delayed implantation in mammals. In keeping with this scenario, the Wnt pathway has been shown to elevate the level of c-myc. Thus, the two pathways seem to converge on c-myc as a common target to promote self-renewal. Whereas LIF does not seem to stimulate self-renewal in human embryonic stem cells it cannot be excluded that other cytokines are involved. The pleiotropic actions of the increasing number of cytokines and receptors signalling via JAKs, STATs and SOCS exhibit considerable redundancy, compensation and plasticity in stem cells in accordance with the view that stem cells are governed by quantitative variations in strength and duration of signalling events known from other cell types rather than qualitatively different stem cell-specific factors.

Gene regulation and priming by topoisomerase IIα in embryonic stem cells

“…It is well established that small molecules such as the interleukin 6 class cytokine LIF are critical regulators of ESC pluripotency 31,46 . Our transcriptome profiling in ESCs lacking TOP2a activity revealed significant changes in gene expression program.…”

“…These genes ARTICLE are enriched for defense and immune response as reflected by many cytokine-related genes. These small molecules are known to contribute to ESC-specific features including maintenance of selfrenewal 31 . Furthermore, 4% of TOP2a target genes that are not expressed in ESCs but become transcriptionally active and occupied by TOP2b in terminal neurons are involved in cell-fate commitment and neurogenesis.…”

Geometric triangular chiral hexagon complexes and clonal embryogenic body organization on the Turin Shroud crucified man image: A predictable tissue response to injury

“…These spectral lines are not uniform, narrowing thin lines pattern in the proximal head area contrast with the broadening lines in distal areas, and its indication of decay energy and changes in the velocity of the molecules in the traversal trajectory. In physics Dicke narrowing is a phenomenon that dramatically reduces the Doppler width of spectral lines, due to frequent velocity-changing collisions [21,22]. A similar phenomenon occurs for electromagnetically induced transparency resonances, and facilitates modeling the spectral line shapes with speed-dependent broadening and Dicke narrowing.…”

Current Research of the Renin-Angiotensin System Effect on Stem Cell Therapy

“…In a study, the administration of Tempol (ROS generation-blocking agent) in Ang II-treated pluripotent stem cells has atenuated the proliferation of stem cells and DNA synthesis suggesting the role of oxidative-signalling pathway in RAS-associated cell proliferation. The other signalling pathway linked to the diferentiation of iPSCs and Ang II is JAK/STAT pathway [59].…”