Article

Stem Cell Reviews and Reports

, Volume 6, Issue 2, pp 270-281

Robust Enhancement of Neural Differentiation from Human ES and iPS Cells Regardless of their Innate Difference in Differentiation Propensity

  • Dae-Sung KimAffiliated withDepartment of Physiology, Brain Korea 21 Project for Medical Science
  • , Jae Souk LeeAffiliated withDepartment of Physiology, Brain Korea 21 Project for Medical Science
  • , Joong Woo LeemAffiliated withDepartment of Physiology, Brain Korea 21 Project for Medical Science
  • , Yong Jun HuhAffiliated withDepartment of Physiology, Brain Korea 21 Project for Medical Science
  • , Ji Young KimAffiliated withDepartment of Physiology, Brain Korea 21 Project for Medical Science
  • , Han-Soo KimAffiliated withDepartment of Laboratory Medicine, Yonsei University College of Medicine
  • , In-Hyun ParkAffiliated withDepartment of Medicine, Division of Pediatric Hematology Oncology, Children’s Hospital Boston, and Dana-Farber Cancer Institute; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
  • , George Q. DaleyAffiliated withDepartment of Medicine, Division of Pediatric Hematology Oncology, Children’s Hospital Boston, and Dana-Farber Cancer Institute; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
  • , Dong-Youn HwangAffiliated withCHA Stem Cell Institute, CHA University College of Medicine Email author 
    • , Dong-Wook KimAffiliated withDepartment of Physiology, Brain Korea 21 Project for Medical ScienceDepartment of Physiology, Center for Cell Therapy, Yonsei University College of Medicine Email author 

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Abstract

Our analyses of three human induced pluripotent stem cell (hiPSC) and six human embryonic stem cell (hESC) lines showed marked variability in differentiation potential into specific lineages, which often hampers their differentiation into specific cell types or cell lineages of interest. Simultaneous inhibition of both Activin/Nodal and BMP pathways with small molecules, SB431542 and dorsomorphin (DM), respectively, promoted significant neural differentiation from all human pluripotent stem cell (hPSC) lines tested, regardless of their differentiation propensity. On the contrary, differentiation into other cell lineages and the number of undifferentiated cells were significantly reduced after differentiation by the dual inhibition. These results demonstrate that innate differentiation propensity of hPSCs could be overcome, at least in part, by modulation of intracellular signaling pathways, resulting in efficient generation of desirable cell types, such as neural cells.

Keywords

Pluripotent stem cell Differentiation propensity Neural induction Cell signaling Small molecule