AI Article Synopsis
- Mouse embryonic stem cells (ESCs) can maintain self-renewal by inhibiting GSK3 and MEK kinases, but the specific roles of MEK's downstream kinases, ERK1 and ERK2, in this process are not fully understood.
- Researchers selectively inhibited or deleted ERK1 and ERK2 to observe their effects on ESC self-renewal and differentiation, finding that ERK1/2 are not essential for ESC survival or self-renewal when both are inhibited alongside GSK3.
- The study reveals that ERK1 and ERK2 have both overlapping and unique functions, with ERK1 promoting mesendoderm differentiation while ERK2 does not, providing insights
Article Abstract
Mouse embryonic stem cell (ESC) self-renewal can be maintained through dual inhibition of GSK3 and MEK kinases. MEK has two highly homologous downstream kinases, extracellular signal-regulated kinase 1 and 2 (ERK1/2). However, the exact roles of ERK1/2 in mouse ESC self-renewal and differentiation remain unclear. We selectively deleted or inhibited ERK1, ERK2, or both using genetic and chemical genetic approaches combined with small molecule inhibitors. The effects of ERK paralog-specific inhibition on mouse ESC self-renewal and differentiation were then assessed. ERK1/2 were found to be dispensable for mouse ESC survival and self-renewal. The inhibition of both ERK paralogs, in conjunction with GSK3 inhibition, was sufficient to maintain mouse ESC self-renewal. In contrast, selective deletion or inhibition of only one ERK paralog did not mimic the effect of MEK inhibition in promoting mouse ESC self-renewal. Regarding ESC differentiation, inhibition of ERK1/2 prevented mesendoderm differentiation. Additionally, selective inhibition of ERK1, but not ERK2, promoted mesendoderm differentiation. These findings suggest that ERK1 and ERK2 have both overlapping and distinct roles in regulating ESC self-renewal and differentiation. This study provides new insights into the molecular mechanisms of ERK1/2 in governing ESC maintenance and lineage commitment, potentially informing future strategies for controlling stem cell fate in research and therapeutic applications.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272557 | PMC |
| http://dx.doi.org/10.3389/fcell.2024.1415621 | DOI Listing |
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