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Extracellular vesicles in tumor-adipose tissue crosstalk: key drivers and therapeutic targets in cancer cachexia

Figure 1. The differentiation process of adipocytes.AMSCs are mesenchymal stem cells that can differentiate into a variety of lineages depending on specific transcription factors. When the Myf-5 factor is absent and the PPARγ and C/EBP proteins are present, AMSCs differentiate into white pre-adipocytes. Upon fat uptake and deposit formation, these adipocytes further differentiate into mature white adipocytes. White adipocytes can also transdifferentiate into beige adipocytes, in a process called white adipocytes browning, in the presence of PRDM16, PPARγ, and PGC-1α. On the other hand, the presence of Myf-5 leads AMSCs to commit to a myogenic lineage. In this lineage, the PRDM16 transcription factor potentiates the AMSC differentiation into brown pre-adipocytes and prevents AMSC differentiation into myoblasts, and further skeletal muscle cells (due to myoD protein and myogenin). In the presence of PPARγ, brown pre-adipocytes mature into brown adipocytes. Other transcription factors, like RUNX2 and Sox9 factors, lead to osteogenic and chondrogenic lineages, respectively. There are also reports that TGF-β released by tumor cells also allows AMSCs to differentiate into myofibroblasts. Created with Biorender.com. AMSCs: Adipose-derived mesenchymal stem cells; Myf-5: myogenic factor 5; PPARγ: peroxisome proliferator-activated receptor-gamma; C/EBP: CCAAT/enhancer binding protein; PRDM16: PR domain containing 16; PGC-1α: PPARgamma-coactivator-1; RUNX2: runt-related transcription factor 2; Sox9: SRY-Box Transcription Factor 9; TGF-β: transforming growth factor-beta.

Extracellular Vesicles and Circulating Nucleic Acids
ISSN 2767-6641 (Online)
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