Researchers are exploring whether these ubiquitous fluorinated molecules might worsen infections or hamper vaccine effectiveness.
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↵1T.O. and J.A.S. contributed equally to this work.
Edited by Floyd E. Bloom, The Scripps Research Institute, La Jolla, CA, and approved January 6, 2009 (received for review September 3, 2008)
Abstract
An intriguing question in human embryonic stem cell (hESC) biology is whether these pluripotent cells can give rise to stably expandable somatic stem cells, which are still amenable to extrinsic fate instruction. Here, we present a pure population of long-term self-renewing rosette-type hESC-derived neural stem cells (lt-hESNSCs), which exhibit extensive self-renewal, clonogenicity, and stable neurogenesis. Although lt-hESNSCs show a restricted expression of regional transcription factors, they retain responsiveness to instructive cues promoting the induction of distinct subpopulations, such as ventral midbrain and spinal cord fates. Using lt-hESNSCs as a donor source for neural transplantation, we provide direct evidence that hESC-derived neurons can establish synaptic connectivity with the mammalian nervous system. Combining long-term stability, maintenance of rosette-properties and phenotypic plasticity, lt-hESNSCs may serve as useful tool to study mechanisms of human NSC self-renewal, lineage segregation, and functional in vivo integration.
Footnotes
- 2To whom correspondence should be addressed. E-mail: brustle{at}uni-bonn.de
Author contributions: P.K. and O.B. designed research; P.K., T.O., J.A.S., and J.L. performed research; P.K., T.O., J.A.S., J.L., and O.B. analyzed data; and P.K. and O.B. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
A rosette-type, self-renewing human ES cell-derived neural stem cell with potential for in vitro instruction and synaptic integration
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