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Mitochondrial Abundant Heat Soluble (MAHS) Protein Expression Modulates Metabolic Dynamics in Human Adipose-Derived
Jordan L Rolsma1, Julieanna Li1, Ruthia Soh2,3
1Department of Bioengineering, University of California, Riverside, CA 92521, USA.
None:
Adipose-derived stem cells (ASCs) possess substantial regenerative potential, with lineage fate tightly coupled to metabolic dynamics. In prior work, we found that expression of the tardigrade-derived protein Mitochondrial Abundant Heat Soluble (MAHS) increased stress tolerance and promoted ASC osteogenic differentiation over adipogenic differentiation, although the mechanism remained unclear. Here, we leverage transcriptomic and functional assays to investigate how MAHS expression influences ASC metabolism. Transcriptomic profiling revealed incomplete adipogenic activation alongside upregulation of ossification-associated genes (e.g., SERPINF1), as well as broader changes in metabolic, Wnt, and YAP signaling pathways consistent with a shift toward osteogenic programming. Functionally, MAHS-expressing ASCs exhibited increased matrix calcium deposition in osteogenic culture, as well as decreased ATP and cAMP levels during basal culture. Further, treatment with forskolin increased cAMP levels, while forskolin or Compound C increased lipid accumulation in MAHS-expressing ASCs. Together, these findings suggest that MAHS expression perturbs metabolic dynamics and signaling networks in ASCs and may contribute to impaired adipogenesis and reinforcement of osteogenic bias. More broadly, this work highlights potential regulatory points that could be targeted to restore lineage balance in metabolically disrupted ASCs.
