The neuro-glial properties of adipose-derived adult stromal (ADAS) cells are not regulated by Notch 1 and are not derived from neural crest lineage.
We investigated whether adipose-derived adult stromal (ADAS) are of neural crest origin and the extent to which Notch 1 regulates their growth and differentiation. Mouse ADAS cells cultured in media formulated for neural stem cells (NSC) displayed limited capacity for self-renewal, clonogenicity, an...
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Public Library of Science (PLoS)
2008-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001453&type=printable |
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| author | Philip C Wrage Thi Tran Khai To Edward W Keefer Kelly A Ruhn John Hong Supriya Hattangadi Isaac Treviño Malú G Tansey |
| author_facet | Philip C Wrage Thi Tran Khai To Edward W Keefer Kelly A Ruhn John Hong Supriya Hattangadi Isaac Treviño Malú G Tansey |
| author_sort | Philip C Wrage |
| collection | DOAJ |
| description | We investigated whether adipose-derived adult stromal (ADAS) are of neural crest origin and the extent to which Notch 1 regulates their growth and differentiation. Mouse ADAS cells cultured in media formulated for neural stem cells (NSC) displayed limited capacity for self-renewal, clonogenicity, and neurosphere formation compared to NSC from the subventricular zone in the hippocampus. Although ADAS cells expressed Nestin, GFAP, NSE and Tuj1 in vitro, exposure to NSC differentiation supplements did not induce mature neuronal marker expression. In contrast, in mesenchymal stem cell (MSC) media, ADAS cells retained their ability to proliferate and differentiate beyond 20 passages and expressed high levels of Nestin. In neuritizing cocktails, ADAS cells extended processes, downregulated Nestin expression, and displayed depolarization-induced Ca(2+) transients but no spontaneous or evoked neural network activity on Multi-Electrode Arrays. Deletion of Notch 1 in ADAS cell cultures grown in NSC proliferation medium did not significantly alter their proliferative potential in vitro or the differentiation-induced downregulation of Nestin. Co-culture of ADAS cells with fibroblasts that stably expressed the Notch ligand Jagged 1 or overexpression of the Notch intracellular domain (NICD) did not alter ADAS cell growth, morphology, or cellular marker expression. ADAS cells did not display robust expression of neural crest transcription factors or genes (Sox, CRABP2, and TH); and lineage tracing analyses using Wnt1-Cre;Rosa26R-lacZ or -EYFP reporter mice confirmed that fewer than 2% of the ADAS cell population derived from a Wnt1-positive population during development. In summary, although media formulations optimized for MSCs or NSCs enable expansion of mouse ADAS cells in vitro, we find no evidence that these cells are of neural crest origin, that they can undergo robust terminal differentiation into functionally mature neurons, and that Notch 1 is likely to be a key regulator of their cellular and molecular characteristics. |
| format | Article |
| id | doaj-art-5dea0d50e0bd4c09bc98dc4ec5d19f7c |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2008-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-5dea0d50e0bd4c09bc98dc4ec5d19f7c2025-08-20T02:00:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-0131e145310.1371/journal.pone.0001453The neuro-glial properties of adipose-derived adult stromal (ADAS) cells are not regulated by Notch 1 and are not derived from neural crest lineage.Philip C WrageThi TranKhai ToEdward W KeeferKelly A RuhnJohn HongSupriya HattangadiIsaac TreviñoMalú G TanseyWe investigated whether adipose-derived adult stromal (ADAS) are of neural crest origin and the extent to which Notch 1 regulates their growth and differentiation. Mouse ADAS cells cultured in media formulated for neural stem cells (NSC) displayed limited capacity for self-renewal, clonogenicity, and neurosphere formation compared to NSC from the subventricular zone in the hippocampus. Although ADAS cells expressed Nestin, GFAP, NSE and Tuj1 in vitro, exposure to NSC differentiation supplements did not induce mature neuronal marker expression. In contrast, in mesenchymal stem cell (MSC) media, ADAS cells retained their ability to proliferate and differentiate beyond 20 passages and expressed high levels of Nestin. In neuritizing cocktails, ADAS cells extended processes, downregulated Nestin expression, and displayed depolarization-induced Ca(2+) transients but no spontaneous or evoked neural network activity on Multi-Electrode Arrays. Deletion of Notch 1 in ADAS cell cultures grown in NSC proliferation medium did not significantly alter their proliferative potential in vitro or the differentiation-induced downregulation of Nestin. Co-culture of ADAS cells with fibroblasts that stably expressed the Notch ligand Jagged 1 or overexpression of the Notch intracellular domain (NICD) did not alter ADAS cell growth, morphology, or cellular marker expression. ADAS cells did not display robust expression of neural crest transcription factors or genes (Sox, CRABP2, and TH); and lineage tracing analyses using Wnt1-Cre;Rosa26R-lacZ or -EYFP reporter mice confirmed that fewer than 2% of the ADAS cell population derived from a Wnt1-positive population during development. In summary, although media formulations optimized for MSCs or NSCs enable expansion of mouse ADAS cells in vitro, we find no evidence that these cells are of neural crest origin, that they can undergo robust terminal differentiation into functionally mature neurons, and that Notch 1 is likely to be a key regulator of their cellular and molecular characteristics.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001453&type=printable |
| spellingShingle | Philip C Wrage Thi Tran Khai To Edward W Keefer Kelly A Ruhn John Hong Supriya Hattangadi Isaac Treviño Malú G Tansey The neuro-glial properties of adipose-derived adult stromal (ADAS) cells are not regulated by Notch 1 and are not derived from neural crest lineage. PLoS ONE |
| title | The neuro-glial properties of adipose-derived adult stromal (ADAS) cells are not regulated by Notch 1 and are not derived from neural crest lineage. |
| title_full | The neuro-glial properties of adipose-derived adult stromal (ADAS) cells are not regulated by Notch 1 and are not derived from neural crest lineage. |
| title_fullStr | The neuro-glial properties of adipose-derived adult stromal (ADAS) cells are not regulated by Notch 1 and are not derived from neural crest lineage. |
| title_full_unstemmed | The neuro-glial properties of adipose-derived adult stromal (ADAS) cells are not regulated by Notch 1 and are not derived from neural crest lineage. |
| title_short | The neuro-glial properties of adipose-derived adult stromal (ADAS) cells are not regulated by Notch 1 and are not derived from neural crest lineage. |
| title_sort | neuro glial properties of adipose derived adult stromal adas cells are not regulated by notch 1 and are not derived from neural crest lineage |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001453&type=printable |
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