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SOX9 is required for maintenance of the pancreatic progenitor cell pool.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2007 Feb 06; Vol. 104 (6), pp. 1865-70. Date of Electronic Publication: 2007 Jan 31. - Publication Year :
- 2007
-
Abstract
- 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.
- Subjects :
- Animals
Cell Differentiation genetics
Cell Differentiation physiology
Cell Proliferation
Cell Survival genetics
Cell Survival physiology
Female
High Mobility Group Proteins deficiency
High Mobility Group Proteins genetics
Mice
Mice, Knockout
Mice, Transgenic
Pancreas metabolism
Pluripotent Stem Cells metabolism
SOX9 Transcription Factor
Signal Transduction genetics
Signal Transduction physiology
Transcription Factors deficiency
Transcription Factors genetics
High Mobility Group Proteins physiology
Pancreas cytology
Pancreas physiology
Pluripotent Stem Cells physiology
Transcription Factors physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 104
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 17267606
- Full Text :
- https://doi.org/10.1073/pnas.0609217104