Modeling abnormal early development with induced pluripotent stem cells from aneuploid syndromes
Wen Li1, Xianming Wang, Wenxia Fan
1Stem Cell and Cancer Biology Group, Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Human Molecular Genetics
|September 28, 2011
Summary
Induced pluripotent stem cells (iPSCs) were generated from aneuploid syndromes, including Turner syndrome (TS). TS iPSCs revealed impaired placentation, not a differentiation blockade, as the cause of abnormal organogenesis and early lethality.
Area of Science:
- Developmental biology
- Genetics
- Stem cell research
Background:
- Aneuploid syndromes, caused by chromosome number alterations, are severe developmental diseases with significant prenatal and postnatal consequences.
- Understanding gene dosage effects in aneuploidies is crucial for potential therapeutic targets and explaining phenotypic diversity.
Purpose of the Study:
- To generate induced pluripotent stem cell (iPSC) lines from various aneuploid syndromes for improved understanding.
- To investigate the cellular and molecular mechanisms underlying Turner syndrome (TS) using iPSCs.
Main Methods:
- Generation of iPSCs from individuals with Turner syndrome (monosomy X), trisomy 8, trisomy 13, and partial trisomy 11;22.
- Characterization of iPSC lines for karyotype stability and embryonic stem cell-like behavior.
- Global gene expression analysis and directed differentiation of TS iPSCs into neural, hepatocyte, and heart lineages.
Main Results:
- Generated stable iPSC lines maintaining donor karyotypes for multiple aneuploidies.
- TS iPSCs exhibited reduced expression of pseudoautosomal genes ASMTL and PPP2R3B.
- TS iPSCs differentiated into various cell types but showed impaired upregulation of CSF2RA, suggesting placental abnormalities.
Conclusions:
- Abnormal organogenesis and early lethality in Turner syndrome are likely linked to impaired placentation rather than a general tissue-specific differentiation defect.
- Generated aneuploid iPSC lines serve as valuable tools for studying developmental diseases and gene dosage effects.
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