Integration of Signaling Pathways with the Epigenetic Machinery in the Maintenance of Stem Cells

Figure 1

Signaling affecting stem cells identity and their interplay with chromatin. Key signaling pathways and relative factors contributing to the maintenance of mESCs (a) or hESCs/EpiSCs (b) identity or to their differentiation (see details in the main text). Black circles in (a) indicate the two chemicals used in the 2i culturing medium (CHIR99021 and PD03). Solid black arrows and lines indicate positive or negative modulation, respectively. Dashed black lines indicate indirect effects. Colored circles with “P” indicate phosphorylation. (c) Key examples of signaling to chromatin in ESCs. The upper panels are relative to a more differentiated state in which the LIF/Stat3 and Nanog targets are repressed while developmental genes are active. Lower panels, instead, describe embryonic stem cells chromatin features. On the right, effect of Jak2, or its constitutive active form Jak2V617F, on H3Y41P and HP1 loading on chromatin. In the middle, interconnection between Erk1/2 and the loading of PRC2 and RNA polymerase II activity at developmental genes. On the left, interplay between the esBAF complex and Stat3 in regulating LIF/Stat3 signaling pathway targets. Details of each example are reported in the main text.

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