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Generation and Comparison of Human Down Syndrome-Induced Pluripotent Stem Cells from Two Types of Cells
Du Rong, Luo Yumei, Wang Ding, Sun Xiaofang, Chen Yaoyong*
(Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Hereditary of the Universities in Guangdong Province, the Third Affiliated Hospital of Guangzhou Medical College, Guangzhou 510150, China
Abstract: Down syndrome (DS)， or Trisomy 21 (T21) syndrome， one of the most common chromosomal abnormalities， is caused by an extra duplication of chromosome 21. The generation of induced pluripotent stem cells (iPSCs) is a critical step in understanding the developmental stages of complex chromosomal diseases. In this study， we have generated DS-specific induced pluripotent stem cells from human amniotic fluid-derived cells and dermal fibroblast cells through lentiviral delivery of four human transcription factors (Oct4/Sox2/Klf4/c-Myc). The DS-iPSCs (Trisomy 21 human amniotic fluid induced pluripotent stem cells， T21 hAF-iPSCs; Trisomy 21 human dermal fibroblast induced pluripotent stem cells， T21 hDF-iPSCs) showed characteristics similar to those of human embryonic stem cells， particularly the morphology and pluripotent-specific transcription-factor (Oct4， Nanog) expression. The pluripotency of DS-iPSCs was also tested in vitro and in vivo. Embryoid bodies and teratomas were formed and showed the expression of differentiated markers for three germ layers. The DS-iPSCs showed a good self-renewal condition and maintained the karyotypes after long-term culturing in vitro. It was found that generation of iPSCs from human amniotic fluid cells were more rapid and efficient than dermal fibroblast cells. Amniotic fluid cells may be a preferred tissue for generating T21-iPSCs.
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