1. Hydrogen sulfide facilitates reprogramming and trans-differentiation in 3D dermal fibroblast.
- Author
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Ostrakhovitch EA, Akakura S, and Tabibzadeh S
- Subjects
- Allyl Compounds pharmacology, Cells, Cultured, Cellular Reprogramming Techniques methods, Cystathionine beta-Synthase genetics, Cystathionine beta-Synthase metabolism, Fibroblasts cytology, Fibroblasts metabolism, Humans, Lactic Acid metabolism, Nanog Homeobox Protein genetics, Nanog Homeobox Protein metabolism, Octamer Transcription Factor-3 genetics, Octamer Transcription Factor-3 metabolism, Osteoblasts cytology, Osteoblasts metabolism, SOXB1 Transcription Factors genetics, SOXB1 Transcription Factors metabolism, Spheroids, Cellular drug effects, Spheroids, Cellular metabolism, Sulfides pharmacology, Cell Transdifferentiation, Cellular Reprogramming, Fibroblasts drug effects, Hydrogen Sulfide metabolism
- Abstract
The efficiency of cell reprogramming in two-dimensional (2D) cultures is limited. Given that cellular stemness is intimately related to microenvironmental changes, 3D cell cultures have the potential of overcoming this limited capacity by allowing cells to self-organize by aggregation. In 3D space, cells interact more efficiently, modify their cellular topology, gene expression, signaling, and metabolism. It is yet not clear as how 3D culture environments modify the reprogramming potential of fibroblasts. We demonstrate that 3D spheroids from dermal fibroblasts formed under ultra-low attachment conditions showed increased lactate production. This is a requisite for cell reprogramming, increase their expression of pluripotency genes, such as OCT4, NANOG and SOX2, and display upregulated cystathionine-β-synthase (CBS) and hydrogen sulfide (H2S) production. Knockdown of CBS by RNAi suppresses lactic acid and H2S production and concomitantly decreases the expression of OCT4 and NANOG. On the contrary, H2S donors, NaHS and garlic-derived diallyl trisulfide (DATS), promote the expression of OCT4, and support osteogenic trans-differentiation of fibroblasts. These results demonstrate that CBS mediated release of H2S regulates the reprogramming of dermal fibroblasts grown in 3D cultures and supports their trans-differentiation., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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