Quantitative Oct4 Overproduction in Mouse Embryonic Stem Cells Results in Prolonged Mesoderm Commitment During Hematopoietic Differentiation In Vitro

The Oct4 transcription factor is essential for the self‐renewal and pluripotency of embryonic stem cells (ESCs). Oct4 level also controls the fate of ESCs. We analyzed the effects of Oct4 overproduction on the hematopoietic differentiation of ESCs. Oct4 was introduced into ESCs via a bicistronic ret...

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Bibliographic Details
Published in:Stem cells (Dayton, Ohio) Ohio), 2006-08, Vol.24 (8), p.1937-1945
Main Authors: Camara‐Clayette, Valérie, Le Pesteur, Françoise, Vainchenker, William, Sainteny, Françoise
Format: Article
Language:English
Subjects:
Animals
Cell differentiation
Cell Differentiation - physiology
Cell Line
Embryonic stem cell
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Developmental
Genetic Vectors - genetics
Green Fluorescent Proteins - genetics
Hematopoiesis
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - physiology
Mesoderm
Mesoderm - cytology
Mesoderm - physiology
Mice
Octamer Transcription Factor-3 - genetics
Octamer Transcription Factor-3 - metabolism
Promoter Regions, Genetic - genetics
Reverse Transcriptase Polymerase Chain Reaction - methods
Transcription factor
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Summary:The Oct4 transcription factor is essential for the self‐renewal and pluripotency of embryonic stem cells (ESCs). Oct4 level also controls the fate of ESCs. We analyzed the effects of Oct4 overproduction on the hematopoietic differentiation of ESCs. Oct4 was introduced into ESCs via a bicistronic retroviral vector, and cells were selected on the basis of Oct4 production, with Oct4+ and Oct42+ displaying twofold and three‐ to fourfold overproduction, respectively. Oct4 overproduction inhibited hematopoietic differentiation in a dose‐dependent manner, after the induction of such differentiation by the formation of day 6 embryoid bodies (EB6). This effect resulted from defective EB6 formation rather than from defective hematopoietic differentiation. In contrast, when hematopoiesis was induced by the formation of blast colonies, the effects of Oct4 depended on the level of overproduction: twofold overproduction increased hematopoietic differentiation, whereas higher levels of overproduction markedly inhibited hematopoietic development. This increase or maintenance of Oct4 levels appears to alter the kinetics and pattern of mesoderm commitment, thereby modifying hemangioblast generation. These results demonstrate that Oct4 acts as a master regulator of ESC differentiation.
ISSN:1066-5099
1549-4918
DOI:10.1634/stemcells.2005-0067