LIM kinases are involved in various cellular events such as migration, cycle, and differentiation, but whether they have a role in the specification of mammalian early endoderm remains unclear. In the present study, we found that depletion of LIMK2 severely inhibited the generation of definitive endoderm (DE) from human embryonic stem cells (hESCs) and promoted an early neuroectodermal fate. Upon the silencing of LIMK2 during the endodermal differentiation, the assembly of actin stress fibers was disturbed, and the phosphorylation of cofilin was decreased. In addition, knockdown of LIMK2 during DE differentiation also interfered the upregulation of epithelial-to-mesenchymal transition (EMT)-related genes and cell migration. Collectively, the results highlight that the serine/threonine kinase LIMK2, acting as a key regulator in actin remodeling, plays a critical role in endodermal lineage determination.

LIM 激酶参与各种细胞事件，如迁移、循环和分化，但它们是否在哺乳动物早期内胚层的规范中发挥作用仍不清楚。在本研究中，我们发现 LIMK2 的消耗严重抑制了人类胚胎干细胞 (hESCs) 定形内胚层 (DE) 的生成，并促进了早期神经外胚层的命运。内胚层分化过程中 LIMK2 沉默后，肌动蛋白应力纤维的组装受到干扰，cofilin 的磷酸化降低。此外，在 DE 分化过程中敲低 LIMK2 也干扰了上皮-间质转化 (EMT) 相关基因和细胞迁移的上调。总的来说，结果强调丝氨酸/苏氨酸激酶 LIMK2 作为肌动蛋白重塑的关键调节剂，