DEPTOR Is a Stemness Factor That Regulates Pluripotency of Embryonic Stem Cells

The mammalian target of rapamycin (mTOR) pathway regulates stem cell regeneration and differentiation in response to growth factors, nutrients, cellular energetics, and various extrinsic stressors. Inhibition of mTOR activity has been shown to enhance the regenerative potential of pluripotent stem cells. DEPTOR is the only known endogenous inhibitor of all known cellular mTOR functions. We show that DEPTOR plays a key role in maintaining stem cell pluripotency by limiting mTOR activity in undifferentiated embryonic stem cells (ESCs). DEPTOR levels dramatically decrease with differentiation of mouse ESCs, and knockdown of DEPTOR is sufficient to promote ESC differentiation. A strong decrease in DEPTOR expression is also observed during human ESCs differentiation. Furthermore, reduction in DEPTOR level during differentiation is accompanied by a corresponding increase in mTOR complex 1 activity in mouse ESCs. Our data provide evidence that DEPTOR is a novel stemness factor that promotes pluripotency and self-renewal in ESCs by inhibiting mTOR signaling.     

胚胎干细胞的基因转录调控

胚胎干细胞作为一种具有多潜能性和自我更新能力的细胞,在人类等高等生物发育中占有重要地位;基于这一特性,胚胎干细胞在临床上具有极其广阔的应用前景。转录因子OCT4、SOX2和NANOG通过调节胚胎干细胞的基因转录,对其多潜能性和自我更新能力具有关键性的调控作用。对这一作用机制的研究,将对人类早期发育的了解和胚胎干细胞的临床应用具有积极意义。     

Transcription Factor Binding to Replicated DNA

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白血病抑制因子与胚胎干细胞

白血病抑制因子对细胞的生长和分化有多种作用,通过与其受体结合传导信号,gp130与LIF受体β链的结合激活JAK激酶(JAK1和JAK2),JAK激酶磷酸化STAT信号转录子,STAT3的磷酸化对于阻止体外培养的干细胞的分化具有十分重要的作用。