[STEM] 確定幹細胞自我維持基態 nature

看板Medicine (醫學生物)作者pathoman (青黏材菌)時間16年前 (2008/05/28 12:48)推噓0(0推 0噓 0→)

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5月22日的《自然》雜志上刊登了科學家最新的研究成果，確定了胚胎幹細胞不確定分化和自我維持的新機制。這一被稱為“幹細胞自我維持基態”的發現，打破了此前關于幹細胞分化和培養的傳統觀點，產生了對胚胎幹細胞增殖調控的新認識。此外，新結果還對人們理解如何控制腫瘤細胞生長具有重要意義。通常，科學家要獲取和維持小鼠胚胎幹細胞，需要將飼養細胞（feeder cells）、條件培養基、細胞因子、生長因子等進行多種經驗主義的組合。因此，他們通常認為，胚胎幹細胞自我更新依賴于多因子激勵。研究表明，人們對胚胎幹細胞如何被操控、實現自我維持的認識是錯誤的。新發現很可能改變許多實驗室的研究方向。與現行的理解相反，新研究表明，胚胎幹細胞的增殖和多能性獨立于外界刺激。如果“屏蔽”掉外來分化信號，胚胎幹細胞將保持不分化狀態。通過利用一些小分子阻斷激活分化過程的化學物質，研究人員發現，胚胎幹細胞的自然“默認態”就是要自我更新或者像通用幹細胞一樣進行增殖。這就意味著，胚胎幹細胞具有先天的自我復制程序。研究人員表示新的小鼠模型研究為人們理解如何在實驗室中生長胚胎幹細胞，提出了一種全新的範式。該發現對于大規模生產特化細胞（如腦細胞、心髒細胞等）以備未來治療之需具有重要意義。到目前為止，科學家只能從少數物種身上獲得胚胎幹細胞。新發現的機制可以促進科學家從更多的物種，比如豬、牛和其他大型動物身上獲得胚胎幹細胞。除了對胚胎幹細胞增殖過程的理解，新研究還為人們帶來了更多關于腫瘤細胞生長的認識，因為這兩類細胞具有很多共性。 nature，453, 519-523 (22 May 2008)， The ground state of embryonic stem cell self-renewal 數字為ref. In the three decades since pluripotent mouse embryonic stem (ES) cells were first described1, 2 they have been derived and maintained by using various empirical combinations of feeder cells, conditioned media, cytokines, growth factors, hormones, fetal calf serum, and serum extracts1, 2, 3, 4, 5, 6, 7. Consequently ES-cell self-renewal is generally considered to be dependent on multifactorial stimulation of dedicated transcriptional circuitries, pre-eminent among which is the activation of STAT3 by cytokines (ref. 8). Here we show, however, that extrinsic stimuli are dispensable for the derivation, propagation and pluripotency of ES cells. Self-renewal is enabled by the elimination of differentiation-inducing signalling from mitogen-activated protein kinase. Additional inhibition of glycogen synthase kinase 3 consolidates biosynthetic capacity and suppresses residual differentiation. Complete bypass of cytokine signalling is confirmed by isolating ES cells genetically devoid of STAT3. These findings reveal that ES cells have an innate programme for self-replication that does not require extrinsic instruction. This property may account for their latent tumorigenicity. The delineation of minimal requirements for self-renewal now provides a defined platform for the precise description and dissection of the pluripotent state. -- ※ 發信站: 批踢踢實業坊(ptt.cc) ◆ From: 133.11.70.111