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BMP signaling pathway is required for commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage
- Source :
- Proceedings of the National Academy of Sciences. 106:12670-12675
- Publication Year :
- 2009
- Publisher :
- Proceedings of the National Academy of Sciences, 2009.
-
Abstract
- Obesity is accompanied by an increase in both adipocyte number and size. The increase in adipocyte number is the result of recruitment to the adipocyte lineage of pluripotent stem cells present in the vascular stroma of adipose tissue. These pluripotent cells have the potential to undergo commitment and then differentiate into adipocytes, as well as myocytes, osteocytes, and chondrocytes. In this article, we show that both bone morphogenetic protein (BMP)2 and BMP4 can induce commitment of C3H10T1/2 pluripotent stem cells into adipocytes. After treatment of C3H10T1/2 stem cells with these BMPs during proliferation followed by exposure to differentiation inducers at growth arrest, nearly all cells enter the adipose development pathway, express specific adipocyte markers, and acquire the adipocyte phenotype. Overexpression of constitutively active BMP receptor (CA)-BMPr1A or CA-BMPr1B induces commitment in the absence of BMP2/4, whereas overexpression of a dominant-negative receptor dominant-negative-BMPr1A suppresses commitment induced by BMP. Also, knockdown of the expression of Smad4 (coregulator in the BMP/Smad signaling pathway) with RNAi disrupts commitment by the BMPs. However, knockdown of expression of p38 MAPK (an intermediary in the BMP/MAPK signaling pathway) with RNAi had little effect on BMP-induced commitment. Together, these findings indicate that the BMP/Smad signaling pathway has a dominant role in adipocyte lineage determination. Proteomic analysis identified lysyl oxidase (LOX), a bona fide downstream target gene of the BMP signaling pathway. Expression of LOX is induced by BMP2/4 during adipocyte lineage commitment, and knockdown of its expression disrupts the commitment process.
- Subjects :
- Pluripotent Stem Cells
medicine.medical_specialty
animal structures
Bone Morphogenetic Protein 2
Smad Proteins
Lysyl oxidase
Bone Morphogenetic Protein 4
SMAD
Biology
Bone Morphogenetic Protein Receptors, Type II
Bone morphogenetic protein
p38 Mitogen-Activated Protein Kinases
Protein-Lysine 6-Oxidase
Mice
chemistry.chemical_compound
Internal medicine
Adipocyte
Adipocytes
medicine
Animals
Cell Lineage
Induced pluripotent stem cell
BMP signaling pathway
Bone Morphogenetic Protein Receptors, Type I
Cells, Cultured
Multidisciplinary
Cell Differentiation
Biological Sciences
BMPR2
Cell biology
Endocrinology
chemistry
embryonic structures
Stem cell
Signal Transduction
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 106
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....32aef07c8a3dfc7ee9c74dffa1468b34