Howard Hughes Medical Institute, Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02142, USA.
Development. 2010 Apr;137(8):1231-41. doi: 10.1242/dev.042051. Epub 2010 Mar 10.
Freshwater planarians are able to regenerate any missing part of their body and have extensive tissue turnover because of the action of dividing cells called neoblasts. Neoblasts provide an excellent system for in vivo study of adult stem cell biology. We identified the Smed-CHD4 gene, which is predicted to encode a chromatin-remodeling protein similar to CHD4/Mi-2 proteins, as required for planarian regeneration and tissue homeostasis. Following inhibition of Smed-CHD4 with RNA interference (RNAi), neoblast numbers were initially normal, despite an inability of the animals to regenerate. However, the proliferative response of neoblasts to amputation or growth stimulation in Smed-CHD4(RNAi) animals was diminished. Smed-CHD4(RNAi) animals displayed a dramatic reduction in the numbers of certain neoblast progeny cells. Smed-CHD4 was required for the formation of these neoblast progeny cells. Together, these results indicate that Smed-CHD4 is required for neoblasts to produce progeny cells committed to differentiation in order to control tissue turnover and regeneration and suggest a crucial role for CHD4 proteins in stem cell differentiation.
淡水涡虫能够再生身体任何缺失的部分，并且由于分裂细胞（称为成体干细胞）的作用，其组织更新率很高。成体干细胞为成年干细胞生物学的体内研究提供了一个极好的系统。我们鉴定了 Smed-CHD4 基因，该基因预测编码一种与 CHD4/Mi-2 蛋白相似的染色质重塑蛋白，这是涡虫再生和组织稳态所必需的。用 RNA 干扰（RNAi）抑制 Smed-CHD4 后，尽管动物无法再生，但成体干细胞的数量最初是正常的。然而，在 Smed-CHD4（RNAi）动物中，成体干细胞对截肢或生长刺激的增殖反应减弱。Smed-CHD4（RNAi）动物中成体干细胞某些后代细胞的数量明显减少。Smed-CHD4 对于这些成体干细胞后代细胞的形成是必需的。总之，这些结果表明，Smed-CHD4 是成体干细胞产生分化后代细胞所必需的，以控制组织更新和再生，并表明 CHD4 蛋白在干细胞分化中起着至关重要的作用。
