Generation of glycosylphosphatidylinositol anchor protein-deficient blood cells from human induced pluripotent stem cells

Xuan Yuan, Evan M. Braunstein, Zhaohui Ye, Cyndi F. Liu, Guibin Chen, Jizhong Zou, Linzhao Cheng, Robert A. Brodsky

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


PIG-A is an X-linked gene required for the biosynthesis of glycosylphosphatidylinositol (GPI) anchors; thus, PIG-A mutant cells have a deficiency or absence of all GPI-anchored proteins (GPI-APs). Acquired mutations in hematopoietic stem cells result in the disease paroxysmal nocturnal hemoglobinuria, and hypomorphic germline PIG-A mutations lead to severe developmental abnormalities, seizures, and early death. Human induced pluripotent stem cells (iPSCs) can differentiate into cell types derived from all three germ layers, providing a novel developmental system for modeling human diseases. Using PIG-A gene targeting and an inducible PIG-A expression system, we have established, for the first time, a conditional PIG-A knockout model in human iPSCs that allows for the production of GPI-AP-deficient blood cells. PIG-A-null iPSCs were unable to generate hematopoietic cells or any cells expressing the CD34 marker and were defective in generating mesodermal cells expressing KDR/VEGFR2 (kinase insert domain receptor) and CD56 markers. In addition, PIG-A-null iPSCs had a block in embryonic development prior to mesoderm differentiation that appears to be due to defective signaling through bone morphogenetic protein 4. However, early inducible PIG-A transgene expression allowed for the generation of GPI-AP-deficient blood cells. This conditional PIG-A knockout model should be a valuable tool for studying the importance of GPI-APs in hematopoiesis and human development.

Original languageEnglish (US)
Pages (from-to)819-829
Number of pages11
JournalStem Cells Translational Medicine
Issue number11
StatePublished - 2013


  • GPI-anchor protein
  • Hematopoiesis
  • Human iPSCs
  • PIG-A gene knockout

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology


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