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01-03-2012

CD44-Positive Cells Are Candidates for Astrocyte Precursor Cells in Developing Mouse Cerebellum

Authors: Na Cai, Masashi Kurachi, Koji Shibasaki, Takayuki Okano-Uchida, Yasuki Ishizaki

Published in: The Cerebellum | Issue 1/2012

Abstract

Neural stem cells are generally considered to be committed to becoming precursor cells before terminally differentiating into either neurons or glial cells during neural development. Neuronal and oligodendrocyte precursor cells have been identified in several areas in the murine central nervous system. The presence of astrocyte precursor cells (APCs) is not so well understood. The present study provides several lines of evidence that CD44-positive cells are APCs in the early postnatal mouse cerebellum. In developing mouse cerebellum, CD44-positive cells, mostly located in the white matter, were positive for the markers of the astrocyte lineage, but negative for the markers of mature astrocytes. CD44-positive cells were purified from postnatal cerebellum by fluorescence-activated cell sorting and characterized in vitro. In the absence of any signaling molecule, many cells died by apoptosis. The surviving cells gradually expressed glial fibrillary acidic protein, a marker for mature astrocytes, indicating that differentiation into mature astrocytes is the default program for these cells. The cells produced no neurospheres nor neurons nor oligodendrocytes under any condition examined, indicating these cells are not neural stem cells. Leukemia inhibitory factor greatly promoted astrocytic differentiation of CD44-positive cells, whereas bone morphogenetic protein 4 (BMP4) did not. Fibroblast growth factor-2 was a potent mitogen for these cells, but was insufficient for survival. BMP4 inhibited activation of caspase-3 and greatly promoted survival, suggesting a novel role for BMP4 in the control of development of astrocytes in cerebellum. We isolated and characterized only CD44 strongly positive large cells and discarded small and/or CD44 weakly positive cells in this study. Further studies are necessary to characterize these cells to help determine whether CD44 is a selective and specific marker for APCs in the developing mouse cerebellum. In conclusion, we succeeded in preparing APC candidates from developing mouse cerebellum, characterized them in vitro, and found that BMPs are survival factors for these cells.

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Title: CD44-Positive Cells Are Candidates for Astrocyte Precursor Cells in Developing Mouse Cerebellum
Authors: Na Cai
Masashi Kurachi
Koji Shibasaki
Takayuki Okano-Uchida
Yasuki Ishizaki
Publication date: 01-03-2012
Publisher: Springer-Verlag
Published in: The Cerebellum / Issue 1/2012
Print ISSN: 1473-4222
Electronic ISSN: 1473-4230
DOI: https://doi.org/10.1007/s12311-011-0294-x

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CD44-Positive Cells Are Candidates for Astrocyte Precursor Cells in Developing Mouse Cerebellum

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