Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency.
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.
Department of Anatomy, School of Medicine and Public Health, University of Wisconsin, Waisman Center, Madison, WI 53705, USA.
Bao-Yang
BY
Hu
Jason P
JP
Weick
Junying
J
Yu
Li-Xiang
LX
Ma
Xiao-Qing
XQ
Zhang
James A
JA
Thomson
Su-Chun
SC
Zhang
D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D009474:Neurons / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D019076:Transgenes
D019485:Bone Morphogenetic Proteins; D005346:Fibroblast Growth Factors