Stem cell-based growth, regeneration, and remodeling of the planarian intestine.

Stem cell-based growth, regeneration, and remodeling of the planarian intestine.
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DOI:
10.1016/j.ydbio.2011.05.669
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发表时间:
2011-08-15
影响因子:
2.7
通讯作者:
Newmark PA
Newmark PA
中科院分区:
生物学3区
文献类型:
--
作者:
Forsthoefel DJ;Park AE;Newmark PA

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虽然有些动物能够再生器官,但实现这一目标的机制尚不清楚。在涡虫中,被称为新生细胞的多能体细胞干细胞为生长提供新细胞,在细胞更新时补充组织,并在损伤后再生组织。然而,对于大多数组织和器官,干细胞分化的时空动态和损伤前存在的组织的命运尚未被系统地表征。利用体内成像和溴脱氧尿嘧啶脉冲追踪实验,我们分析了涡虫肠道的生长和再生,肠道是负责消化和营养分配的器官。在生长过程中,我们观察到新的肠分支沿着整个前后轴增加。我们发现新的肠细胞在整个肠道中分化,而不是在特定的生长区域,这表明分支形态发生主要是通过分化的肠组织的重塑来实现的。在再生过程中,我们还证明了以前未被认识到的肠道重塑程度,其中先前存在的后肠组织对新形成的前肠有广泛的贡献,反之亦然。与生长中的动物相比,新的肠细胞分化发生在优先位置,包括在新生成的组织(胚)内,以及沿着原有的肠分支进行重塑。我们的研究结果表明,涡虫肠道的生长和再生是通过干细胞的协调分化和原有组织的重塑来实现的。阐明这些过程整合的机制对于理解胚胎后的器官发生至关重要。
Although some animals are capable of regenerating organs, the mechanisms by which this is achieved are poorly understood. In planarians, pluripotent somatic stem cells called neoblasts supply new cells for growth, replenish tissues in response to cellular turnover, and regenerate tissues after injury. For most tissues and organs, however, the spatiotemporal dynamics of stem cell differentiation and the fate of tissue that existed prior to injury have not been characterized systematically. Utilizing in vivo imaging and bromodeoxyuridine pulse-chase experiments, we have analyzed growth and regeneration of the planarian intestine, the organ responsible for digestion and nutrient distribution. During growth, we observe that new gut branches are added along the entire anteroposterior axis. We find that new enterocytes differentiate throughout the intestine rather than in specific growth zones, suggesting that branching morphogenesis is achieved primarily by remodeling of differentiated intestinal tissues. During regeneration, we also demonstrate a previously unappreciated degree of intestinal remodeling, in which pre-existing posterior gut tissue contributes extensively to the newly formed anterior gut, and vice versa. By contrast to growing animals, differentiation of new intestinal cells occurs at preferential locations, including within newly generated tissue (the blastema), and along pre-existing intestinal branches undergoing remodeling. Our results indicate that growth and regeneration of the planarian intestine are achieved by coordinated differentiation of stem cells and the remodeling of pre-existing tissues. Elucidation of the mechanisms by which these processes are integrated will be critical for understanding organogenesis in a post-embryonic context.
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