In the present review the authors discussed the identification of selector, or …

• Abstract
• Introduction
• Identification of master switch genes and MyoD
• Transdifferentiation of myoblasts to adipocytes
• In vivo pancreas to liver transdifferentiation
• Conversion of hepatic cells to pancreatic-like cells
• Transdifferentiation of liver to pancreas by ectopic expression of Pdx1
• Hes1 as a suppressor of Ngn3
• Wnt signalling
• Barrett's metaplasia
• Bone marrow transdifferentiation - fact or artefact?
• Summary
• References
• Figures

Biology Articles » Developmental Biology » The molecular basis of transdifferentiation » Transdifferentiation of myoblasts to adipocytes

Transdifferentiation of myoblasts to adipocytes

- The molecular basis of transdifferentiation

Myoblasts and adipocytes arise from the same germlayer of the embryo, the mesoderm, and recent observations suggests it is possible to directly induce the conversion of myoblasts to adipocytes. G8 myoblasts are a tissue-culture model for myogenesis and can differentiate spontaneously into myotubes when cultured in medium containing fetal calf serum. The transcription factors C/EBPα and PPARγ, when expressed in G8 myoblasts, can suppress the musclespecific transcription factors (Myf5, MyoD, myogenin and MRF4) [9]. Conversely, markers specific for adipocytes, such as aP-2, adipsin, lipoprotein lipase and phosphoenolpyruvate carboxykinase appeared in G8 myoblasts co-expressing both PPARγ and C/EBPα. Both C/EBPβ and C/EBPδ also stimulate adipogenesis in fibroblasts [10], which probably occurs through up-regulation of PPARγ expression [11]. However, the normal activation of the PPARγ nuclear receptor in adipogenesis still requires ligand binding [12]. There are also cases where expression of C/EBPα in fibroblast cell lines (such as NIH3T3) will promote adipogenesis [13], but this only occurs with overexpression of C/EBPα. Normally, C/EBPα is expressed later than PPARγ in preadipocyte differentiation, and physiological amounts of C/EBPα can synergize with PPARγ promoting adipogenesis in fibroblasts [14]. It has also been shown that the canonical Wnt signalling pathway is involved in inhibiting preadipocyte differentiation [15], probably through modulating expression of PPARγ and C/EBPα. Understanding the regulation of C/EBPs and PPARγ is important not only for maintaining the adipocyte differentiation state [16], but also in developing potential therapies for obesity.

Transdifferentiation (metaplasia) of endodermally-derived tissues

One of the best-documented examples of transdifferentiation is the switch between liver and pancreas, a conversion that reflects the close developmental relationship between the two tissues [17]. During development, the liver and pancreas arise from adjacent regions of the embryo called the anterior foregut endoderm and may therefore express common transcription factors during the early stage of development. Transdifferentiation of pancreas and liver is observed following the exposure of animals to certain carcinogens or in humans as preneoplastic alterations [reviewed in 18, 19]. The known molecular events underlying the switch between liver and pancreas and other endodermally-derived tissues, such as lung and intestine, or oesophagus and intestine, are discussed below.