Terminal differentiation, induction

The development of a directed differentiation system is hampered by the relative lack of data regarding the inductive cues that lead to commitment and terminal differentiation of human cardiomyocytes. Thus, strategies for directed differentiation should undoubtedly follow the research conducted in a number of model organisms (see Part 111, Chapter 4), most notably the chick, amphibians, zebrafish, and mouse. 

Studies on the effect of ERK and JNK activation on cellular outcome have revealed that the consequence of this activation is cell type specific. While the activation of ERBCs is often proliferative in nature, it may not always be so. For example, the induction of ERK by nerve growth factor in PC12 cells leads to terminal differentiation and exit from the cell cycle [80]. In other cell types, the ability of the cell to survive an insult is often dependent on the balance between ERK and JNK... 

Terminal differentiation of myoblasts and induction of muscle-specific proteins do not occur until myoblasts stop dividing and begin migrating. 

Maintenance of a cisoid restricted conformation about bonds C-6—C-7 and C-12—C-13 (structures types II and III) can provide activity equal to or better than that exhibited by all-rra/w-retinoic acid in most assays. TTNPB (3), TTNN (4), and (R12) (see Table 1.1) are marked by these restrictions and are parents to other type-II retinoids. In the induction of terminal differentiation of HL-60 and U-937 cells, however, removal of the latter conformational restriction results in enhanced activity. The tetramethyl-tetrahydronaphthyl-octatrienoic retinoid (structure type I, X=CMc2, aromatic ring B) is more potent than TTNPB, especially when either retinoid is administered in combination with cytokines (see POTENTIATIVE AND SYNERGISTIC EFFECTS USING RETINOIDS IN COMBINATION WITH CYTOKINES AND OTHER HORMONES below). 

The data presented here demonstrate that the induction of differentiation by DMSO in the human promyelocytic leukaemia cells, HL-60, along the granulocytic lineage does not retard the ability of these cells to repair DNA lesions induced by exposure to either ionising radiation or treatment with the mono-functional methylating agent, DMS. This is consistent with our previous observation that post-mitotic primary muscle cell nuclei undergoing terminal differentiation are as efficient as their pro-... 

Myogenesis in vivo and in vitro involves conversion of cycling and undifferentiated myoblasts to terminally differentiated and noncycling myotubes [1,2]. The sequence of events associated with differentiation of muscle cells in culture has been well defined and involves myoblast proliferation to confluency, cessation of DNA synthesis with irreversible withdrawal of myoblasts from the cell cycle, plasma membrane fusion and formation of multinucleated myotubes, and induction of muscle specific proteins and isoenzymes (e.g., myosin, a-actin, a-tropomysin, creatine phosphokinase, etc.) at the time of onset of fusion [3-5]. 

In order to inactivate a tumor cell, several distinct yet overlapping pathways may be activated. Besides the induction of pure apoptosis, other cell inactivation modalities, including programmed necrosis, mitotic catastrophe, senescence, or terminal differentiation, may be triggered (Belka 2006). The influence of a combined modality treatment on any of these end points has never been analyzed in greater detail thus, only very few data are available showing that the combination of paradigmatic radiation sensitizers with radiation quantitatively alters the induction of certain predefined mechanisms of cell death (Fig. 10.7). 

The Notch signaling pathway is also important for determining cell fate in HF development [87]. Notch signaling acts by blocking cell differentiation, which maintains the competence of undifferentiated cells [88, 89] in both the developing tooth and the HF to respond to inductive signals that determine their developmental fate [87, 90]. Based on expression smdies in the HF, Notch may be a competence factor, as its pattern of expression in the HF appears to be restricted to cells that have left the proliferative pool but have yet to terminally differentiate [91, 92]. 

C. Induction of Terminal Differentiation of Murine Teratocarcinoma Cells... 

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