未分化胚胎細胞轉錄因子(UTF1)是胚胎多功能幹細胞(Embryonic stem ells, ES) 的一項重要指標，它能標示ES細胞是否具有分化成各式細胞的能力 (pluripotency)。但是，UTF1如何影響分化仍不清楚。為了研究UTF1在分化上的角色，我們利用胚胎多功能幹細胞及同樣具有分化能力的胚胎癌細胞(Embryonic carcinoma cells)作研究。由P19胚胎癌細胞中所篩選出的缺乏UTF1表現的細胞株和原本正常的P19細胞比較，我們發現缺乏UTF1的細胞株具有較好的神經分化潛能。在P19細胞中，利用小干擾RNA (siRNA) 抑制UTF1表現也能增進維生素A酸 (Retinoic acid, RA) 誘導產生的神經分化，這結果和我們在缺乏UTF1表現的P19細胞株所得到的結果相同。在缺乏UTF1表現的P19細胞株中，重新表現UTF1會抑制RA誘導產生的神經分化。有趣的是，我們發現減少UTF1並不會影響貼附的未分化P19細胞的生長，但是會讓P19細胞在RA處理的胚胎體狀態時有較好的生長能力。和P19胚胎癌細胞的結果相同, 降低UTF1表現會使得胚胎幹細胞在自發性分化或RA誘導後，外胚層神經細胞標誌GAP43的表現會有明顯增加。所以，我們認為缺乏UTF1表現會容易誘導EC和ES細胞產生神經分化。最近的研究結果顯示, Pin1 (peptidyl-prolyl isomerase 1)可以經由調控 Oct4 和Nanog蛋白的磷酸化而維持胚胎幹細胞的生長及分化。我們證實Pin1可以直接和UTF1結合，但是這結合並不需要UTF1蛋白磷酸化。在P19細胞中，失去對Pin1結合能力的突變型UTF1無法抑制RA誘導的神經分化。因此，實驗結果顯示在P19細胞中，UTF1可以被Pin1調控而有抑制神經分化的功能。

UTF1 (undifferentiated embryonic cell transcription factor 1) is a marker for the pluripotency of embryonic stem (ES) cells but how it affects differentiation remains unclear. To study its role in the process, we used both ES cells and embryonic carcinoma (EC) cells, which are pluripotent teratocarcinoma cells. We found that UTF1-deficient clones, isolated from P19 EC cells, showed higher neuronal-differentiating potential than the parental cell line. Consistent with this observation, suppression of UTF1 expression by RNA interference enhanced retinoic acid (RA)-induced neuronal differentiation in P19 cells. Moreover, reconstitution of UTF1 expression in UTF1-deficient clones decreased their ability to undergo neuronal differentiation. Interestingly, the growth rates of UTF1-deficient P19 cells did not differ from that of parental cells in adherent cultures, but increased in embryoid bodies during RA-induced differentiation. In ES cells, reduction of UTF1 expression increased expression of neuronal-ectoderm marker Gap43 during both spontaneous and RA-induced differentiation; this was consistent with the results in P19 cells. Therefore, we proposed that endogenous UTF1 prevented EC and ES cells from neuronal differentiation, and that the loss of UTF1 directed EC and ES cells toward a neuronal fate. Recently, Pin1, a peptidyl-prolyl isomerase, has been found to maintain self-renewal via modulating phosphorylation of Oct4 and Nanog. We demonstrated that Pin1 bond to UTF1 directly, but surprisingly, this interaction did not require phosphorylation of UTF1. UTF1 mutant that had lost Pin1 binding ability failed to suppress RA-induced neuronal differentiation in P19 cells. These results indicated that the function of UTF1 in inhibition of neuronal differentiation could be regulated by Pin1 in mouse EC cells.

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