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SOX9 is required for maintenance of the pancreatic progenitor cell pool.

Proceedings of the National Academy of Sciences of the United States of America | February 06, 2007 |

Seymour, Philip A | Freude, Kristine K | Tran, Man N | Mayes, Erin E | Jensen, Jan | Kist, Ralf | Scherer, Gerd | Sander, Maike
Seymour, Freude, et al. "SOX9 is required for maintenance of the pancreatic progenitor cell pool." Proceedings of the National Academy of Sciences of the United States of America 104.6 (2007): 1865-70. Web.

Abstract

The factors necessary to maintain organ-specific progenitor cells are poorly understood and yet of extreme clinical importance. Here, we identify the t ... between SOX factors and Notch. These findings will be of major significance for the development of in vitro protocols for cell replacement therapies.

The factors necessary to maintain organ-specific progenitor cells are poorly understood and yet of extreme clinical importance. Here, we identify the transcription factor SOX9 as the first specific marker and maintenance factor of multipotential progenitors during pancreas organogenesis. In the developing pancreas, SOX9 expression is restricted to a mitotically active, Notch-responsive subset of PDX1(+) pluripotent progenitors and is absent from committed endocrine precursors or differentiated cells. Similar to Notch mutations, organ-specific Sox9 inactivation in mice causes severe pancreatic hypoplasia resulting from depletion of the progenitor cell pool. We show that Sox9 maintains pancreatic progenitors by stimulating their proliferation, survival, and persistence in an undifferentiated state. Our finding that SOX9 regulates the Notch-effector HES1 suggests a Notch-dependent mechanism and establishes a possible genetic link between SOX factors and Notch. These findings will be of major significance for the development of in vitro protocols for cell replacement therapies.

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Fig 1. Seymour, Freude, et al. "SOX9 is required for maintenance of the pancreatic progenitor cell pool." Proceedings of the National Academy of Sciences of the United States of America 104.6 (2007): 1865-70. Web.
Zpq0040749740001
Fig 1. Seymour, Freude, et al. "SOX9 is required for maintenance of the pancreatic progenitor cell pool." Proceedings of the National Academy of Sciences of the United States of America 104.6 (2007): 1865-70. Web.

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Fig 2. Seymour, Freude, et al. "SOX9 is required for maintenance of the pancreatic progenitor cell pool." Proceedings of the National Academy of Sciences of the United States of America 104.6 (2007): 1865-70. Web.
Zpq0040749740002
Fig 2. Seymour, Freude, et al. "SOX9 is required for maintenance of the pancreatic progenitor cell pool." Proceedings of the National Academy of Sciences of the United States of America 104.6 (2007): 1865-70. Web.

Fig 2

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Zpq0040749740003
Fig 3. Seymour, Freude, et al. "SOX9 is required for maintenance of the pancreatic progenitor cell pool." Proceedings of the National Academy of Sciences of the United States of America 104.6 (2007): 1865-70. Web.
Zpq0040749740003
Fig 3. Seymour, Freude, et al. "SOX9 is required for maintenance of the pancreatic progenitor cell pool." Proceedings of the National Academy of Sciences of the United States of America 104.6 (2007): 1865-70. Web.

Fig 3

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Fig 4. Seymour, Freude, et al. "SOX9 is required for maintenance of the pancreatic progenitor cell pool." Proceedings of the National Academy of Sciences of the United States of America 104.6 (2007): 1865-70. Web.
Zpq0040749740004
Fig 4. Seymour, Freude, et al. "SOX9 is required for maintenance of the pancreatic progenitor cell pool." Proceedings of the National Academy of Sciences of the United States of America 104.6 (2007): 1865-70. Web.

Fig 4

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Fig 5. Seymour, Freude, et al. "SOX9 is required for maintenance of the pancreatic progenitor cell pool." Proceedings of the National Academy of Sciences of the United States of America 104.6 (2007): 1865-70. Web.
Zpq0040749740005
Fig 5. Seymour, Freude, et al. "SOX9 is required for maintenance of the pancreatic progenitor cell pool." Proceedings of the National Academy of Sciences of the United States of America 104.6 (2007): 1865-70. Web.

Fig 5

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