7月19日,Science杂志在线报道,科学家揭示了食管上皮细胞(EE)单个祖细胞群即可完成EE组织的维持和修复两项任务。
食管上皮细胞(EE)的疾病,如返流性食管炎和癌症,发病率正在上升。尽管这样,EE的稳态维持和修复的细胞生物学仍存在许多争议。
本研究发现,在小鼠中,EE是由单个细胞群随机分裂生成所维持的。这些祖细胞以相同的概率分裂产生增殖性的或分化性的子细胞。
受到全反式维甲酸(atRA)刺激,子细胞命运的平衡性仍保持不变,但细胞分裂的速度增加了。然而,受损伤后,细胞可逆性地转换到生产过量的增殖性子细胞,直到伤口愈合。这种命运的开关,使得单个的祖细胞群就能够行使维持和修复组织的功能,而无须"储备"一个循环缓慢的干细胞池。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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A Single Progenitor Population Switches Behavior to Maintain and Repair Esophageal Epithelium
David P. Doupé1,4,*,Maria P. Alcolea1,*,Amit Roshan1,Gen Zhang2,Allon M. Klein2,3,Benjamin D. Simons2,4,Philip H. Jones1,?
Diseases of the esophageal epithelium (EE), such as reflux esophagitis and cancer, are rising in incidence. Despite this, the cellular behaviors underlying EE homeostasis and repair remain controversial. Here, we show that in mice, EE is maintained by a single population of cells that divide stochastically to generate proliferating and differentiating daughters with equal probability. In response to challenge with all-trans retinoic acid (atRA), the balance of daughter cell fate is unaltered, but the rate of cell division increases. However, following wounding, cells reversibly switch to producing an excess of proliferating daughters until the wound has closed. Such fate-switching enables a single progenitor population to both maintain and repair tissue without the need for a “reserve” slow-cycling stem cell pool.