Involvement of LIMK2 in actin cytoskeleton remodeling during the definitive endoderm differentiation

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.

Automated summary

The study revealed that LIMK2 plays a critical role in the generation of definitive endoderm from human embryonic stem cells, impacting actin stress fiber assembly, cell migration, and the expression of epithelial-to-mesenchymal transition-related genes. The results underscore the importance of LIMK2 as a key regulator in endodermal lineage determination.