Brown-like adipose progenitors derived from human induced pluripotent stem cells: Identification of critical pathways governing their adipogenic capacity.
Brown-like adipose progenitors derived from human induced pluripotent stem cells: Identification of critical pathways governing their adipogenic capacity.
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DOI：
10.1038/srep32490
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发表时间：
2016-08-31
影响因子：
4.6
通讯作者：
Dani C
中科院分区：
文献类型：
--
作者：
Hafner AL;Contet J;Ravaud C;Yao X;Villageois P;Suknuntha K;Annab K;Peraldi P;Binetruy B;Slukvin II;Ladoux A;Dani C
人诱导多能干细胞（hiPSC）显示出用于肥胖治疗的巨大前景，因为它们代表棕色/棕色脂肪祖细胞（BAP）的无限来源。然而，当维持在传统的脂肪形成混合物中时，与成人-BAP相比，hiPSC-BAP显示出低的脂肪形成能力。这一特征的原因尚不清楚，阻碍了它们在基于细胞的治疗和基础研究中的应用。在这里，我们表明，用TGFβ通路抑制剂SB 431542与抗坏血酸和EGF一起处理是促进hiPSCs-BAP分化所需的，其水平与成人BAP分化相似。hiPSC-BAP表达具有棕色（ZIC 1）和棕色（CD 137）脂肪细胞标志物的成人UCP 1表达细胞（PAX 3、CIDEA、DIO 2）的分子同一性。总而言之，这些数据强调了TGFβ途径在关闭hiPSC棕色脂肪形成中的关键作用，并揭示了解锁其分化的新因素。由于hiPSC-BAP显示出与成人BAP的相似性，因此它为开发替代策略以对抗肥胖开辟了新的机会。
Human induced pluripotent stem cells (hiPSCs) show great promise for obesity treatment as they represent an unlimited source of brown/brite adipose progenitors (BAPs). However, hiPSC-BAPs display a low adipogenic capacity compared to adult-BAPs when maintained in a traditional adipogenic cocktail. The reasons of this feature are unknown and hamper their use both in cell-based therapy and basic research. Here we show that treatment with TGFβ pathway inhibitor SB431542 together with ascorbic acid and EGF were required to promote hiPSCs-BAP differentiation at a level similar to adult-BAP differentiation. hiPSC-BAPs expressed the molecular identity of adult-UCP1 expressing cells (PAX3, CIDEA, DIO2) with both brown (ZIC1) and brite (CD137) adipocyte markers. Altogether, these data highlighted the critical role of TGFβ pathway in switching off hiPSC-brown adipogenesis and revealed novel factors to unlock their differentiation. As hiPSC-BAPs display similarities with adult-BAPs, it opens new opportunities to develop alternative strategies to counteract obesity.