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Abstract
Adipogenic differentiation of visceral adipose tissue-resident multipotent mesenchymal stromal cells (VA-MSC) into adipocytes is metabolically protective. This study identifies IFNγ and TGFβ as key inhibitors of primary human VA-MSC differentiation. IFNγ/JAK2-activated STAT5 and TGFβ-activated Smad3 physically interact via Smad4, preventing early adipogenic commitment by suppressing pro-adipogenic transcription factors. Disrupting IFNγ-TGFβ synergy rescued adipogenesis. The STAT5-Smad4-Smad3 complex is a central mechanism regulating MSC plasticity.
Publisher
npj Regenerative Medicine
Published On
Aug 31, 2022
Authors
Rahul Das, Jayeeta Giri, Pradyut K. Paul, Nicole Froelich, Raghavan Chinnadurai, Sara McCoy, Wade Bushman, Jacques Galipeau
Tags
adipogenic differentiation
VA-MSC
IFNγ
TGFβ
transcription factors
STAT5
Smad3

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