Weiyi Liu's research while affiliated with Purdue University and other places

Supplementary material

Agilent microarray results showing genes up-regulated and down-regulated in N1ICD-mdx versus mdx muscles.DOI: http://dx.doi.org/10.7554/eLife.17355.013

ELife digest Muscles do much more than enable the body to move; they are also important organs involved in the metabolism. Conditions ranging from muscular dystrophy to insulin resistance result from problems that affect muscle tissue. Hence, understanding the signaling mechanisms that regulate how muscles develop and work will be critical to improving muscle-related health conditions. To form and repair muscles, muscle progenitor cells develop (or differentiate) into new muscle cells, which then fuse to form muscle fibers. A signaling pathway involving a protein known as Notch regulates how cells communicate during development, and has been shown to play a key role in muscle progenitor cells. However, it was not known what role Notch signaling plays in the differentiated muscle cells. Bi, Yue et al. have now studied genetically modified mice in which Notch signaling could be manipulated in certain types of cells. In mice with increased Notch signaling in both their newly differentiated muscle cells and muscle fibers, any unfused muscle cells were forced to return to an undifferentiated state, a process called dedifferentiation. This led to the muscles wasting away and resulted in the mice dying young. By contrast, in mice that only experienced activated Notch signaling in their muscle fibers, no dedifferentiation was seen. However, aged and dystrophic muscles in these mice regained the ability to contract and regenerate. Bi, Yue et al. hope that these findings will transform into new strategies to activate or inactivate Notch signaling at different stages of muscle development or regeneration. This could help to repair muscles under various disease conditions. DOI: http://dx.doi.org/10.7554/eLife.17355.002

miR-133a inhibits adipocyte browning in SAT. SAT SVFs were transfected with synthetic miRNA133a by electroporation and cultured to confluence, followed by adipogenic induction and differentiation for 4 days each. (A–C) qPCR analysis of miR-133a and the brown markers after cells were differentiated. N = 3, *P<0.05, **P<0.01. (TIF)

Relative expression of miroRNAs in various subcutaneous WAT depots. asWAT, anterior subcutaneous WAT; bsWAT, back subcutaneous WAT; ingWAT, inguinal WAT. The expression of bsWAT is normalized to 1. N = 3. *P<0.05, **P<0.01. (TIF)

Knockdown of miR-133a upregulates UCP1 expression. Depots of asWAT and ingWAT were harvested from widltype (WT) and miR-133a knockdown (KO; miR-133a1−/−a2+/−) mice that were housed at room temperature or at 4°C for 5 days. Pictured are representative Western Blot images showing the relative expression levels of UCP1. Beta-Actin is used as internal control for protein input. (TIF)

Brown adipose tissues (BAT) are derived from a Myf5-expressing cell lineage and white adipose tissues (WAT) predominantly arise from non-Myf5 lineages, though a subpopulation of adipocytes in some WAT depots can be derived from the Myf5-lineage. However, the functional implication of the Myf5 and non-Myf5 lineage cells in WAT is unclear. We found that the Myf5-lineage constitution in subcutaneous WAT depots is negatively correlated to the expression of classical BAT and newly defined beige/brite adipocyte-specific genes. Consistently, FACS-purified Myf5-lineage adipo-progenitors give rise to adipocytes expressing lower levels of BAT-specific Ucp1, Prdm16, Cidea and Ppargc1a genes and beige adipocyte-specific CD137, Tmem26 and Tbx1 genes compared to the non-Myf5-lineage adipocytes from the same depots. Ablation of the Myf5-lineage progenitors in WAT stromal vascular cell cultures leads to increased expression of BAT and beige cell signature genes. Strikingly, the Myf5-lineage cells in WAT are heterogeneous and contain distinct adipogenic (Sca1+) and myogenic (Sca1-) progenitors. The latter differentiate robustly into myofibers in vitro and in vivo, and restore dystrophin expression after transplantation into mdx mouse, a model for Duchenne muscular dystrophy. These results demonstrate the heterogeneity and functional differences of the Myf5- and non-Myf5-lineage cells in the white adipose tissue.