Wang Chen, Han Xiao-Shuai, Li Fang-Fang, Huang Shuang, Qin Yong-Wen, Zhao Xian-Xian, Jing Qing
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine & Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai, China.
Department of Cardiology, Changhai Hospital , Shanghai, China.
Cell Discov. 2016 Aug 2;2:16029. doi: 10.1038/celldisc.2016.29. eCollection 2016.
Pigmentation processes occur from invertebrates to mammals. Owing to the complexity of the pigmentary system, in vivo animal models for pigmentation study are limited. Planarians are capable of regenerating any missing part including the dark-brown pigments, providing a promising model for pigmentation study. However, the molecular mechanism of planarian body pigmentation is poorly understood. We found in an RNA interference screen that a forkhead containing transcription factor, Albino, was required for pigmentation without affecting survival or other regeneration processes. In addition, the body color recovered after termination of Albino double stranded RNA feeding owing to the robust stem cell system. Further expression analysis revealed a spatial and temporal correlation between Albino and pigmentation process. Gene expression arrays revealed that the expression of three tetrapyrrole biosynthesis enzymes, ALAD, ALAS and PBGD, was impaired upon Albino RNA interference. RNA interference of PBGD led to a similar albinism phenotype caused by Albino RNA interference. Moreover, PBGD was specifically expressed in pigment cells and can serve as a pigment cell molecular marker. Our results revealed that Albino controls planarian body color pigmentation dominantly via regulating tetrapyrrole biogenesis. These results identified Albino as the key regulator of the tetrapyrrole-based planarian body pigmentation, suggesting a role of Albino during stem cell-pigment cell fate decision and provided new insights into porphyria pathogenesis.
色素沉着过程从无脊椎动物到哺乳动物都有发生。由于色素系统的复杂性,用于色素沉着研究的体内动物模型有限。涡虫能够再生任何缺失的部分,包括深棕色色素,这为色素沉着研究提供了一个有前景的模型。然而,涡虫身体色素沉着的分子机制尚不清楚。我们在RNA干扰筛选中发现,一种含叉头结构域的转录因子Albino是色素沉着所必需的,且不影响生存或其他再生过程。此外,由于强大的干细胞系统,在停止喂食Albino双链RNA后身体颜色得以恢复。进一步的表达分析揭示了Albino与色素沉着过程之间的时空相关性。基因表达阵列显示,在Albino RNA干扰后,三种四吡咯生物合成酶ALAD、ALAS和PBGD的表达受到损害。PBGD的RNA干扰导致了与Albino RNA干扰相似的白化病表型。此外,PBGD在色素细胞中特异性表达,可作为色素细胞的分子标记。我们的结果表明,Albino主要通过调节四吡咯生物合成来控制涡虫身体颜色色素沉着。这些结果确定Albino是基于四吡咯的涡虫身体色素沉着的关键调节因子,提示了Albino在干细胞-色素细胞命运决定中的作用,并为卟啉症发病机制提供了新的见解。