MYCL-mediated reprogramming expands pancreatic insulin-producing cells
MYCL-mediated reprogramming expands pancreatic insulin-producing cells
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DOI：
10.1038/s42255-022-00530-y
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发表时间：
2022-02-10
影响因子：
20.8
通讯作者：
Yamada，Yasuhiro
中科院分区：
文献类型：
--
作者：
Hirano，Michitada;So，Yusei;Yamada，Yasuhiro
β细胞再生能力有限，易患糖尿病。在此，我们发现，在MYC家族成员中，Mycl1在胰腺内分泌细胞的增殖中起着关键作用。基因切除Mycl1导致新生小鼠胰腺内分泌细胞增殖减少。相反，成年小鼠Myclin的表达促进了β和α细胞的增殖，并且在Myclin表达取消后细胞仍然存在。在这种退出后，扩大的α细胞的一部分会产生产生胰岛素的细胞。体内瞬时Mycl1的表达足以使糖尿病小鼠的高血糖正常化。在体外，MyCL的表达同样会刺激胰岛细胞的活跃复制，即使是那些来自老龄小鼠的细胞也是如此。最后，我们证明了MYCL刺激成人身体胰岛细胞的分裂。我们的结果表明，Myclone的诱导扩大了功能性β细胞群，这可能为β细胞提供一种再生策略。
β cells have a limited capacity for regeneration, which predisposes towards diabetes. Here, we show that, of the MYC family members,Myclplays a key role in proliferation of pancreatic endocrine cells. Genetic ablation ofMyclcauses a reduction in the proliferation of pancreatic endocrine cells in neonatal mice. By contrast, the expression ofMyclin adult mice stimulates the proliferation of β and α cells, and the cells persist after withdrawal ofMyclexpression. A subset of the expanded α cells give rise to insulin-producing cells after this withdrawal. TransientMyclexpression in vivo is sufficient to normalize the hyperglycaemia of diabetic mice. In vitro expression ofMyclsimilarly provokes active replication in islet cells, even in those from aged mice. Finally, we show thatMYCLstimulates the division of human adult cadaveric islet cells. Our results demonstrate that the induction ofMyclalone expands the functional β-cell population, which may provide a regenerative strategy for β cells.