Here we show that mouse Apg12-Apg5 conjugate localizes to the isolation membranes in mouse embryonic stem cells.
We recently found in yeast that a novel ubiquitin-like system, the Apg12-Apg5 conjugation system, is essential for autophagy. However, how the isolation membranes are formed is poorly understood. In macroautophagy, cytoplasmic components are delivered to lysosomes for degradation via autophagosomes that are formed by closure of cup-shaped isolation membranes. We conclude that blockade of lineage-specific transcription factors by Id proteins enables the self-renewal response to LIF/STAT3. Upon LIF withdrawal, Id-expressing ES cells differentiate but do not give rise to neural lineages. Forced expression of Id liberates ES cells from BMP or serum dependence and allows self-renewal in LIF alone. The critical contribution of BMP is to induce expression of Id genes via the Smad pathway. ES cells can be propagated from single cells and derived de novo without serum or feeders using LIF plus BMP. Here, we report that bone morphogenetic proteins (BMPs) act in combination with LIF to sustain self-renewal and preserve multilineage differentiation, chimera colonization, and germline transmission properties. In serum-free cultures, however, LIF is insufficient to block neural differentiation and maintain pluripotency. The cytokine leukemia inhibitory factor (LIF) drives self-renewal of mouse embryonic stem (ES) cells by activating the transcription factor STAT3. Of development and is likely to play important roles in tissue homeostasis and stem That allows recognition and elimination of defective cells during the early stages Cell competition is, therefore, a process Of differential c-Myc levels is critical and that c-Myc overexpression is sufficient Furthermore, during this process, we find that establishment This elimination occurs in an apoptosis-dependent manner and is
Or defective autophagy or that are tetraploid are eliminated at the onset of differentiationīy wild-type cells. We find that ESCs displaying defective bone morphogenetic protein signaling That cell competition is a mechanism regulating the fitness of embryonic stem cells Would compromise their ability to contribute to further development.
A fundamental question in developmental biology is whether there are mechanisms toĭetect stem cells with mutations that, although not adversely affecting viability,
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