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Direct Reprogramming of Melanocytes to Neural Crest Stem‐Like Cells by One Defined Factor
Mouse and human somatic cells can either be reprogrammed to a pluripotent state or converted to another lineage with a combination of transcription factors suggesting that lineage commitment is a reversible process. Here we show that only one factor, the active intracellular form of Notch1, is suffi...
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Published in: | Stem cells (Dayton, Ohio) Ohio), 2011-11, Vol.29 (11), p.1752-1762 |
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container_title | Stem cells (Dayton, Ohio) |
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creator | Zabierowski, Susan E. Baubet, Valerie Himes, Benjamin Li, Ling Fukunaga‐kalabis, Mizuho Patel, Sonal McDaid, Ronan Guerra, Matt Gimotty, Phyllis Dahamne, Nadia Herlyn, Meenhard |
description | Mouse and human somatic cells can either be reprogrammed to a pluripotent state or converted to another lineage with a combination of transcription factors suggesting that lineage commitment is a reversible process. Here we show that only one factor, the active intracellular form of Notch1, is sufficient to convert mature pigmented epidermal‐derived melanocytes into functional multipotent neural crest (NC) stem‐like cells. These induced NC stem cells (iNCSCs) proliferate as spheres under stem cell media conditions, re‐express NC‐related genes, and differentiate into multiple NC‐derived mesenchymal and neuronal lineages. Moreover, iNCSCs are highly migratory and functional in vivo. These results demonstrate that mature melanocytes can be reprogrammed toward their primitive NC cell precursors through the activation of a single stem cell‐related pathway. Reprogramming of melanocytes to iNCSCs may provide an alternate source of NCSCs for neuroregenerative applications. STEM CELLS 2011;29:1752–1762 |
doi_str_mv | 10.1002/stem.740 |
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Here we show that only one factor, the active intracellular form of Notch1, is sufficient to convert mature pigmented epidermal‐derived melanocytes into functional multipotent neural crest (NC) stem‐like cells. These induced NC stem cells (iNCSCs) proliferate as spheres under stem cell media conditions, re‐express NC‐related genes, and differentiate into multiple NC‐derived mesenchymal and neuronal lineages. Moreover, iNCSCs are highly migratory and functional in vivo. These results demonstrate that mature melanocytes can be reprogrammed toward their primitive NC cell precursors through the activation of a single stem cell‐related pathway. Reprogramming of melanocytes to iNCSCs may provide an alternate source of NCSCs for neuroregenerative applications. 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STEM CELLS 2011;29:1752–1762</description><subject>Animals</subject><subject>Blotting, Western</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - physiology</subject><subject>Cell Line</subject><subject>Cell Movement - genetics</subject><subject>Cell Movement - physiology</subject><subject>Cellular Reprogramming - genetics</subject><subject>Cellular Reprogramming - physiology</subject><subject>Chick Embryo</subject><subject>Dedifferentiation</subject><subject>Humans</subject><subject>Melanocytes</subject><subject>Melanocytes - cytology</subject><subject>Melanocytes - metabolism</subject><subject>Neural Crest - cytology</subject><subject>Neural crest stem cells</subject><subject>Neural Stem Cells - cytology</subject><subject>Neural Stem Cells - metabolism</subject><subject>Notch</subject><subject>Receptor, Notch1 - genetics</subject><subject>Receptor, Notch1 - metabolism</subject><subject>Reprogramming</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - metabolism</subject><issn>1066-5099</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNp1kctu1DAUhi0EoqUg8QTIO9ik-Bbb2SCh6Q1p2kq0rFhYZ5yTwZDEUzsDml0fgWfkSerRlKosWNmSP33_Of4Jec3ZIWdMvM8TDodGsSdkn9eqqVTD7dNyZ1pXNWuaPfIi5--McVVb-5zsCd4oW9d2n3w9Cgn9RD_jKsVlgmEI45LGjp5jD2P0mwkznSK9wHWCns4S5olelbg_t7_n4QfSGfZ9posNvRyRHmEXRmzpCfgpppfkWQd9xlf35wH5cnJ8PTur5penn2Yf55VXpmaVbbwRUiyElqC06XwrjYBWglAcgS-01EIAMCs6661RAEagZqrTqm5aYPKAfNh5V-vFgK3HcSqzulUKA6SNixDcvy9j-OaW8aeTmteGySJ4ey9I8WZdNnRDyL4sBiPGdXYNY8ZIbbdR73akTzHnhN1DCmduW4XbVuFKFQV983iqB_Dv3xeg2gG_Qo-b_4rc1fXx-VZ4B4ANlME</recordid><startdate>201111</startdate><enddate>201111</enddate><creator>Zabierowski, Susan E.</creator><creator>Baubet, Valerie</creator><creator>Himes, Benjamin</creator><creator>Li, Ling</creator><creator>Fukunaga‐kalabis, Mizuho</creator><creator>Patel, Sonal</creator><creator>McDaid, Ronan</creator><creator>Guerra, Matt</creator><creator>Gimotty, Phyllis</creator><creator>Dahamne, Nadia</creator><creator>Herlyn, Meenhard</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201111</creationdate><title>Direct Reprogramming of Melanocytes to Neural Crest Stem‐Like Cells by One Defined Factor</title><author>Zabierowski, Susan E. ; 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Here we show that only one factor, the active intracellular form of Notch1, is sufficient to convert mature pigmented epidermal‐derived melanocytes into functional multipotent neural crest (NC) stem‐like cells. These induced NC stem cells (iNCSCs) proliferate as spheres under stem cell media conditions, re‐express NC‐related genes, and differentiate into multiple NC‐derived mesenchymal and neuronal lineages. Moreover, iNCSCs are highly migratory and functional in vivo. These results demonstrate that mature melanocytes can be reprogrammed toward their primitive NC cell precursors through the activation of a single stem cell‐related pathway. Reprogramming of melanocytes to iNCSCs may provide an alternate source of NCSCs for neuroregenerative applications. STEM CELLS 2011;29:1752–1762</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>21948558</pmid><doi>10.1002/stem.740</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Blotting, Western Cell Differentiation - genetics Cell Differentiation - physiology Cell Line Cell Movement - genetics Cell Movement - physiology Cellular Reprogramming - genetics Cellular Reprogramming - physiology Chick Embryo Dedifferentiation Humans Melanocytes Melanocytes - cytology Melanocytes - metabolism Neural Crest - cytology Neural crest stem cells Neural Stem Cells - cytology Neural Stem Cells - metabolism Notch Receptor, Notch1 - genetics Receptor, Notch1 - metabolism Reprogramming Stem Cells - cytology Stem Cells - metabolism |
title | Direct Reprogramming of Melanocytes to Neural Crest Stem‐Like Cells by One Defined Factor |
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