Notch/RBP-J signaling regulates epidermis/hair fate determination of hair follicular stem cells
Notch/RBP-J signaling regulates epidermis/hair fate determination of hair follicular stem cells
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DOI：
10.1016/s0960-9822(03)00081-2
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发表时间：
2003-02-18
期刊：
影响因子：
9.2
通讯作者：
Honjo, T
中科院分区：
文献类型：
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作者：
Yamamoto, N;Tanigaki, K;Honjo, T
Notch信号传导参与各种细胞谱系的细胞命运决定[1-9]。Notch与其配体的相互作用诱导其胞内结构域（IC）的切割[10]，Notch IC易位至细胞核并结合RBP-J [11]以反式激活靶基因的转录[10，12]。哺乳动物中的所有四种Notch [13-17]都与RBP-J结合以发挥其反式激活活性。Notch在发育或分化的表皮和毛发中表达[13-15，18-20]，抑制表皮的终末分化[21]，并调节毛发分化[22]。存在于毛囊上部（凸起）的常见干细胞有助于表皮和毛细胞形成[23，24]。然而，目前还不清楚是什么决定了毛囊干细胞将成为头发或表皮。在这里，我们报告了以嵌合模式有条件地破坏小鼠RBP-J基因以避免RBP-J缺陷的胚胎致死性[25]，导致脱发，表皮角化过度和表皮囊肿形成。囊肿形成可能是由于RBP-J缺陷干细胞向表皮祖细胞的异常命运决定及其向表皮的加速分化的组合。这些结果表明，Notch/RBP-J信号调节毛囊干细胞在隆突区的细胞命运决定。
Notch signaling is involved in the cell fate determination of various cell lineages [1-9]. Notch interaction with its ligand induces the cleavage of its intracellular domain (IC) [10], and the Notch IC translocates to the nucleus and binds to RBP-J [11] to transactivate transcription of target genes [10, 12]. All four Notches in mammals [13-17] bind to RBP-J to exert their transactivation activities. Notch is expressed in developing or differentiating epidermis and hairs [13-15, 18-20], inhibits the terminal differentiation of the epidermis [21], and regulates hair differentiation [22]. The common stem cells that reside in the upper portion of hair follicles (the bulge) contribute to epidermal and hair cell formation [23, 24]. However, it is unknown what determines whether hair follicular stem cells will become hairs or epidermis. Here we report that conditionally disrupting the mouse RBP-J gene in a mosaic pattern to avoid embryonic lethality of RBP-J-deficiency [25] caused hair loss, epidermal hyperkeratinization, and epidermal cyst formation. Cyst formation is probably due to a combination of the aberrant fate determination of RBP-J-deficient stem cells to epidermal progenitors and their accelerated differentiation into epidermis. These results suggest that Notch/RBP-J signaling regulates the cell fate determination of hair follicular stem cells at the bulge region.