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Biology subjects

Hinte, L. C.

Publications and source records attributed to Hinte, L. C..

2 recordsLinked to original sources

Generation of functional adipoids from human induced pluripotent stem cells

Human adipose tissue models are lacking although essential for metabolic research. Traditional primary cell cultures are poorly scalable and unsuitable for drug screening or modeling of genetic disease. Conventional two-dimensional adipocyte cultures cannot withstand the long-term treatment required to mimic chronic conditions such as obesity and insulin resistance. To overcome these limitations, we developed an accessible protocol to produce three-dimensional human induced pluripotent stem cell (hiPSC)-derived adipocyte microtissues, termed adipoids. hiPSC-derived adipoids display long-term stability and viability. Single-nucleus RNA sequencing revealed that adipoids contain mature adipocytes and adipocyte stem/progenitor cells, similar to human adipose tissue. Furthermore, hiPSC-derived adipoids contain unilocular adipocytes, exhibit stimulated lipolysis, and secrete adipokines. Thus, hiPSC-derived adipoids provide a functional, scalable and genetically tractable model to perform large-scale pharmacological screens and to investigate human metabolic disease.

molecular biology↗

Exercise promotes satellite cell contribution to myofibers in a load-dependent manner

Satellite cells (SCs) are required for muscle repair following injury and are involved in muscle remodeling upon muscular contractions. Exercise stimulates SC accumulation and myonuclear accretion. To what extent exercise training at different mechanical loads drive SC contribution to myonuclei however is unknown. By performing SC fate tracing experiments, we show that 8-weeks of voluntary wheel running increased SC contribution to myonuclei in mouse plantar flexor muscles in a load-dependent but fiber type-independent manner. Increased SC fusion however was not exclusively linked to muscle hypertrophy as wheel running without external load substantially increased SC fusion in the absence of fiber hypertrophy. Due to nuclear propagation, nuclear fluorescent fate tracing mouse models were inadequate to quantify SC contribution to myonuclei. Ultimately, by performing fate tracing at the DNA level, we show that SC contribution mirrors myonuclear accretion during exercise. Collectively, these findings provide direct evidence that mechanical load during exercise independently promotes SC contribution to existing myofibers.

cell biology↗