Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency

doi:10.1073/pnas.0910012107

Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency

^aWaisman Center,
^bGenome Center,
^cDepartment of Anatomy, and
^dDepartment of Neurology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705

Edited by Rudolf Jaenisch, Whitehead Institute for Biomedical Research, Cambridge, MA, and approved January 19, 2010 (received for review September 1, 2009)

Abstract

For the promise of human induced pluripotent stem cells (iPSCs) to be realized, it is necessary to ask if and how efficiently they may be differentiated to functional cells of various lineages. Here, we have directly compared the neural-differentiation capacity of human iPSCs and embryonic stem cells (ESCs). We have shown that human iPSCs use the same transcriptional network to generate neuroepithelia and functionally appropriate neuronal types over the same developmental time course as hESCs in response to the same set of morphogens; however, they do it with significantly reduced efficiency and increased variability. These results were consistent across iPSC lines and independent of the set of reprogramming transgenes used to derive iPSCs as well as the presence or absence of reprogramming transgenes in iPSCs. These findings, which show a need for improving differentiation potency of iPSCs, suggest the possibility of employing human iPSCs in pathological studies, therapeutic screening, and autologous cell transplantation.

Footnotes

¹To whom correspondence should be addressed. E-mail: Zhang{at}waisman.wisc.edu.
Author contributions: B.-Y.H., J.A.T., and S.-C.Z. designed research; B.-Y.H., J.P.W., J.Y., L.-X.M., X.-Q.Z., and S.-C.Z. performed research; B.-Y.H., J.P.W., J.Y., and S.-C.Z. analyzed data; and B.-Y.H., J.P.W., J.Y., X.-Q.Z., J.A.T., and S.-C.Z. wrote the paper.
Conflict of interest statement: J.A.T. is a founder, stock owner, consultant, and board member of Cellular Dynamics International (CDI). He also serves as a scientific advisor to and has financial interests in Tactics II Stem Cell Ventures.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0910012107/DCSupplemental.