Simultaneous control of stemness and differentiation by the transcription factor Escargot in adult stem cells: How can we tease them apart?

Simultaneous control of stemness and differentiation by the transcription factor Escargot in adult stem cells: How can we tease them apart?
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DOI:
10.1080/19336934.2016.1176650
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发表时间:
2016-01-01
期刊:
FLY
影响因子:
1.2
通讯作者:
Jones, D. Leanne
Jones, D. Leanne
中科院分区:
生物学4区
文献类型:
--
作者:
Loza-Coll, Mariano A.;Jones, D. Leanne

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成体器官的稳态周转和损伤后的再生能力取决于干细胞自我更新(以维持或扩大干细胞库)和分化(以取代失去的组织)之间的平衡。我们最近已经表征了果蝇蜗牛家族转录因子蜗牛(esg)在睾丸囊肿干细胞(CySC)(1,2)和肠干细胞(ISCs)中的作用。(3,4)esg的CySC突变体不能维持为干细胞,但它们仍然能够沿着囊细胞谱系正常分化。相比之下,产生紧密相关谱系(顶端中枢细胞)的esg突变型CySC不能维持中枢细胞身份。类似地,Esg维持ISCs的干性,同时调节祖细胞向吸收性肠上皮细胞或分泌性肠内分泌细胞的终末分化。因此,我们的研究结果表明,Esg可能在成体干细胞中发挥保守和关键的调节作用,控制其维持和终末分化。在这里,我们提出,这种双重监管作用是由于同时控制的重叠遗传程序的Esg和讨论的令人兴奋的挑战和机遇,摆在面前的实验探索的潜在机制。
The homeostatic turnover of adult organs and their regenerative capacity following injury depend on a careful balance between stem cell self-renewal (to maintain or enlarge the stem cell pool) and differentiation (to replace lost tissue). We have recently characterized the role of the Drosophila Snail family transcription factor escargot (esg) in testis cyst stemcells (CySCs)(1,2) and intestinal stem cells (ISCs).(3,4) CySCs mutant for esg are not maintained as stem cells, but they remain capable of differentiating normally along the cyst cell lineage. In contrast, esg mutant CySCs that give rise to a closely related lineage, the apical hub cells, cannot maintain hub cell identity. Similarly, Esg maintains stemness of ISCs while regulating the terminal differentiation of progenitor cells into absorptive enterocytes or secretory enteroendocrine cells. Therefore, our findings suggest that Esg may play a conserved and pivotal regulatory role in adult stem cells, controlling both their maintenance and terminal differentiation. Here we propose that this dual regulatory role is due to simultaneous control by Esg of overlapping genetic programs and discuss the exciting challenges and opportunities that lie ahead to explore the underlying mechanisms experimentally.