Table 1.
Examples of Cellular Fate Change within the Pancreas
| Cellular Transition | Modifier | Mechanism of Action | Target Cell Identity |
Converted Cell Fate Identity |
Degree of Fate Change |
Setting | References |
|---|---|---|---|---|---|---|---|
| Dedifferentiation | pharmacological induction of metabolic and inflammatory injury | excessive digestive enzyme release | acinar cell | dedifferentiated acinar cell | ++ | in vivo | Jensen et al., 2005; Morris et al., 2010a; Folias et al., 2014 |
| genetic manipulation of transcription factors/signaling pathways and metabolic stress | repression of canonical β cell gene function | β cell | dedifferentiated β cell | ++ | in vivo, in vitro | Landsman et al., 2011; Talchai et al., 2012; Puri et al., 2013; Guo et al., 2013; Wang et al., 2014; Blum et al., 2014 | |
| Transdifferentiation: intermediary reprogramming | cellular injury due to pancreatic duct ligation | activation of an embryonic gene expression program | acinar cell | multipotent progenitor cell | +++ | in vivo | Pan et al., 2013 |
| genetic manipulation of transcription factors | transcriptional modulation of gene expression | β cell | α cell, δ cell | ++++ | in vivo | Talchai et al., 2012; Puri et al., 2013; Gao et al., 2014 | |
| toxin-mediated death of β cells, causing diabetes | transcriptional regulation of gene expression | α cell, δ cell | β cell | ++++ | in vivo | Thorel et al., 2010; Chera et al., 2014 | |
| Transdifferentiation: direct reprogramming | forced expression of key transcription factors | transcriptional regulation of gene expression | acinar cell | α cell, β cell, δ cell | ++++ | in vivo | Zhou et al., 2008; Li et al., 2014 |
| cytokine and growth factors | activation of STAT3 signaling | acinar cell | β cell | ++++ | in vivo, in vitro | Baeyens et al., 2006; Baeyens et al., 2009; Baeyens et al., 2014 | |
| modulation of epigenomic elements | derepression of the Arx promoter through DNA methylation | β cell | α cell | ++++ | in vivo | Dhawan et al., 2011; Papizan et al., 2011 | |
| Resting | physiological event | metabolic stress | β cell, acinar cell | β cell, acinar cell | + | in vivo | predicted |
| Transformation | oncogenic mutations in K-ras | activation of genetic/signaling programs | acinar cell, duct cell | PANIN, IPMN | +++++ | in vivo | Guerra et al., 2007; De La O et al., 2008; Morris et al., 2010a; Kopp et al., 2012; von Figura et al., 2014a |
Distinct modifiers can cause conversion of adult pancreatic cells into other differentiated cell types through multiple mechanisms.