Muscle stem cell dysfunction impairs muscle regeneration in a mouse model of Down syndrome.
Muscle stem cell dysfunction impairs muscle regeneration in a mouse model of Down syndrome.
复制标题
肌肉干细胞功能障碍会损害唐氏综合症小鼠模型的肌肉再生。
DOI：
10.1038/s41598-018-22342-5
复制
发表时间：
2018
影响因子：
4.6
通讯作者：
Olwin,BradleyB
中科院分区：
文献类型：
--
作者：
Pawlikowski,Bradley;Betta,NicoleDalla;Elston,Tiffany;Williams,DarianA;Olwin,BradleyB
由21三体引起的唐氏综合征的特征在于多种医学病症，包括智力障碍、心血管缺陷、血细胞紊乱和过早衰老表型。唐氏综合征中有几个体干细胞群功能失调，它们的缺陷可能导致多种唐氏综合征表型。唐氏综合症与肌无力有关，但唐氏综合症中的骨骼肌干细胞或卫星细胞尚未研究。我们发现，卫星细胞扩增的失败损害了Ts65Dn唐氏综合征小鼠模型的肌肉再生。Ts65Dn卫星细胞积累DNA损伤并过度表达Usp16，Usp16是一种调节DNA损伤反应的组蛋白去泛素化酶。随着Ts65Dn小鼠年龄的增长，卫星细胞功能的损害进一步下降，强调干细胞缺陷是唐氏综合征病理学的重要贡献者。
Down syndrome, caused by trisomy 21, is characterized by a variety of medical conditions including intellectual impairments, cardiovascular defects, blood cell disorders and pre-mature aging phenotypes. Several somatic stem cell populations are dysfunctional in Down syndrome and their deficiencies may contribute to multiple Down syndrome phenotypes. Down syndrome is associated with muscle weakness but skeletal muscle stem cells or satellite cells in Down syndrome have not been investigated. We find that a failure in satellite cell expansion impairs muscle regeneration in the Ts65Dn mouse model of Down syndrome. Ts65Dn satellite cells accumulate DNA damage and over express Usp16, a histone de-ubiquitinating enzyme that regulates the DNA damage response. Impairment of satellite cell function, which further declines as Ts65Dn mice age, underscores stem cell deficiencies as an important contributor to Down syndrome pathologies.