Potency and Fate Specification in CNS Stem Cell Populations In Vitro

Rea Ravin, Daniel J. Hoeppner, David M. Munno, Liran Carmel, Jim Sullivan, David L. Levitt, Jennifer L. Miller, Christopher Athaide, David M. Panchision, Ronald D.G. McKay*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

96 Scopus citations


To realize the promise of stem cell biology, it is important to identify the precise time in the history of the cell when developmental potential is restricted. To achieve this goal, we developed a real-time imaging system that captures the transitions in fate, generating neurons, astrocytes, and oligodendrocytes from single CNS stem cells in vitro. In the presence of bFGF, tripotent cells normally produce specified progenitors through a bipotent intermediate cell type. Surprisingly, the tripotent state is reset at each passage. The cytokine CNTF is thought to instruct multipotent cells to an astrocytic fate. We demonstrate that CNTF both directs astrogliogenesis from tripotent cells, bypassing two of the three normal bipotent intermediates, and later promotes the expansion of specified astrocytic progenitors. These results show how discrete cell types emerge from a multipotent cell and provide a strong basis for future studies to determine the molecular basis of fate specification.

Original languageAmerican English
Pages (from-to)670-680
Number of pages11
JournalCell Stem Cell
Issue number6
StatePublished - 4 Dec 2008
Externally publishedYes

Bibliographical note

Funding Information:
Several students contributed to the manual annotation of lineages in development of this project, including Daniel Ahmad, Kathleen Bandt, Elizabeth Baumel, Vince Beachley, Pavana Beerelli, Alissa Berliner, Sarah Gan, Brinda Gupta, Daniel Holohan, Josh Lieberman, Reut Mushkat, Christopher Nabel, Meghan Nelson, Emily Prentice, Nicole Ramsey, Jean Suh, and Sahar Zadeh. Professors Ralf Schnabel and Anja-Kristin Schulz provided a script for extracting data from SIMI°BioCell. The authors thank Kang Li and Takeo Kanade (Carnegie Mellon University) for the image stabilizer plugin to ImageJ and Wayne Rasband (NIH) for supporting ImageJ. This research was supported by the Intramural Research Program of the NIH, NINDS.




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