P38alpha in Mouse Embryonic Stem Cells

Summary

Principal Investigator: Yan Lin Guo
Abstract: [unreadable] DESCRIPTION (provided by applicant): p38 mitogen activated protein (MAP) kinases are widely expressed protein kinases that regulate growth and development. p38alpha is the most abundant isoform expressed in mammalian cells. Depending on cell types and the nature of stimuli, p38alpha regulates a wide range of physiological processes, such as cell proliferation, survival, and differentiation. Its pivotal role in embryogenesis is best demonstrated in p38alpha knockout (p38a-/-) mice where embryos display defective vascularization and vessel structures, suggesting a critical role of p38alpha in the development of vascular system. p38alpha knockout is lethal, thus limited information can be obtained from animal models. However, the embryonic stem (ES) cells isolated from knockout embryos (p38a-/-ES cells) are viable, which can be a valuable cell system to analyze the specific functions of p38alpha. p38alpha has been intensively studied in somatic cells, but we know little of its functions in ES cells. We have shown that p38a-/-ES cells display several altered properties from wild type ES cells, including cell adhesion, morphology and viability. The goals of this proposal are: 1. to further characterize several lines of p38a and p38a-/-ES cells and to determine the molecular mechanisms underlying the altered properties of ES cells caused by p38alpha deletion, 2. to investigate the role of p38alpha in ES differentiation, specifically focusing on how the ability of ES cells to differentiate to endothelial cells (ECs) is affected in p38a-/-ES cell, and 3. to analyze ES cell-differentiated EC function by an 3-dimendsional (3D) in vitro angiogenesis model. In this model, ECs will be cultured in a 3D collagen matrix, where they undergo a series of morphological changes to form tube-like structures, mimicking the steps of in vivo blood vessel formation. This novel assay will be used as a functional analysis to test hypothesis that ECs derived from p38a-/-ES cells may retain certain abilities to differentiate, but differentiated cells may have impaired functions to assemble into normal vessels. This study is expected to provide well characterized and genetically defined pSSalpha deficiency ES cell lines, which will be particularly useful for in-depth investigation of the roles of pSSalpha in ES cell differentiation and vascular development. The knowledge derived from this study could be valuable for the development of cell-based therapeutic approaches for diseases associated with angiogenesis and cardiovascular malfunction. [unreadable] [unreadable] [unreadable]
Funding Period: 2006-07-31 - 2009-05-31
more information: NIH RePORT

Top Publications

  1. pmc Transient inhibition of cell proliferation does not compromise self-renewal of mouse embryonic stem cells
    Ruoxing Wang
    Department of Biological Sciences, The University of Southern Mississippi, 118 College Drive 5018, Hattiesburg, MS 39406, USA
    Exp Cell Res 318:2094-104. 2012
  2. pmc Mouse embryonic stem cells have underdeveloped antiviral mechanisms that can be exploited for the development of mRNA-mediated gene expression strategy
    Ruoxing Wang
    1 Department of Biological Sciences, The University of Southern Mississippi, Hattiesburg, Mississippi
    Stem Cells Dev 23:594-604. 2014
  3. pmc Effects of oxidative stress on mouse embryonic stem cell proliferation, apoptosis, senescence, and self-renewal
    Yan Lin Guo
    Department of Biological Sciences, The University of Southern Mississippi, Hattiesburg, Mississippi 39406, USA
    Stem Cells Dev 19:1321-31. 2010
  4. pmc Biocompatibility of synthetic poly(ester urethane)/polyhedral oligomeric silsesquioxane matrices with embryonic stem cell proliferation and differentiation
    Yan Lin Guo
    Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, MS 39406, USA
    J Tissue Eng Regen Med 4:553-64. 2010
  5. ncbi Altered cell adhesion and cell viability in a p38alpha mitogen-activated protein kinase-deficient mouse embryonic stem cell line
    Yan Lin Guo
    Department of Biological Sciences, The University of Southern Mississippi, Hattiesburg, MS 39406, USA
    Stem Cells Dev 15:655-64. 2006
  6. ncbi NF-kappaB, but not p38 MAP kinase, is required for TNF-alpha-induced expression of cell adhesion molecules in endothelial cells
    Suja Rajan
    Department of Biological Sciences, The University of Southern Mississippi, Hattiesburg, Mississippi 39406, USA
    J Cell Biochem 105:477-86. 2008
  7. pmc Mouse embryonic stem cells lacking p38alpha and p38delta can differentiate to endothelial cells, smooth muscle cells, and epithelial cells
    Samujjwal Chakraborty
    Department of Biological Sciences, The University of Southern Mississippi, Hattiesburg, MS 39406, USA
    Differentiation 78:143-50. 2009

Scientific Experts

  • Yan Lin Guo
  • Ruoxing Wang
  • Faqing Huang
  • Samujjwal Chakraborty
  • Suja Rajan
  • Joseph Spangler
  • Jundi Wang
  • Chengwen Teng
  • Baobin Kang
  • Jianming Ye
  • Shanshan Bai

Detail Information

Publications7

  1. pmc Transient inhibition of cell proliferation does not compromise self-renewal of mouse embryonic stem cells
    Ruoxing Wang
    Department of Biological Sciences, The University of Southern Mississippi, 118 College Drive 5018, Hattiesburg, MS 39406, USA
    Exp Cell Res 318:2094-104. 2012
    ..Together, our data suggest that short-term inhibition of cell proliferation does not compromise the basic properties of mESCs...
  2. pmc Mouse embryonic stem cells have underdeveloped antiviral mechanisms that can be exploited for the development of mRNA-mediated gene expression strategy
    Ruoxing Wang
    1 Department of Biological Sciences, The University of Southern Mississippi, Hattiesburg, Mississippi
    Stem Cells Dev 23:594-604. 2014
    ..Therefore, mRNA-based gene expression could be developed into a novel ESC differentiation strategy that avoids safety concerns associated with viral/DNA-based vectors in regenerative medicine. ..
  3. pmc Effects of oxidative stress on mouse embryonic stem cell proliferation, apoptosis, senescence, and self-renewal
    Yan Lin Guo
    Department of Biological Sciences, The University of Southern Mississippi, Hattiesburg, Mississippi 39406, USA
    Stem Cells Dev 19:1321-31. 2010
    ..In conclusion, our data suggest that ESCs are sensitive to H(2)O(2) toxicity, but may have unique mechanisms that prevent H(2)O(2)-induced senescence and protect self-renewal capacity...
  4. pmc Biocompatibility of synthetic poly(ester urethane)/polyhedral oligomeric silsesquioxane matrices with embryonic stem cell proliferation and differentiation
    Yan Lin Guo
    Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, MS 39406, USA
    J Tissue Eng Regen Med 4:553-64. 2010
    ..The excellent compatibility between the PEU/POSS matrix and ESC proliferation/differentiation demonstrates the potential of using PEU/POSS polymers in future ESC-based tissue engineering...
  5. ncbi Altered cell adhesion and cell viability in a p38alpha mitogen-activated protein kinase-deficient mouse embryonic stem cell line
    Yan Lin Guo
    Department of Biological Sciences, The University of Southern Mississippi, Hattiesburg, MS 39406, USA
    Stem Cells Dev 15:655-64. 2006
    ..Together our results indicated that p38alpha may negatively regulate mouse ES cell adhesion and viability...
  6. ncbi NF-kappaB, but not p38 MAP kinase, is required for TNF-alpha-induced expression of cell adhesion molecules in endothelial cells
    Suja Rajan
    Department of Biological Sciences, The University of Southern Mississippi, Hattiesburg, Mississippi 39406, USA
    J Cell Biochem 105:477-86. 2008
    ..The inhibition of SB at 10 microM on TNF-alpha-induced ICAM-1, VCAM-1 and E-selectin is likely due to the nonspecific effect of SB...
  7. pmc Mouse embryonic stem cells lacking p38alpha and p38delta can differentiate to endothelial cells, smooth muscle cells, and epithelial cells
    Samujjwal Chakraborty
    Department of Biological Sciences, The University of Southern Mississippi, Hattiesburg, MS 39406, USA
    Differentiation 78:143-50. 2009
    ..Our results highlight the possibility that p38 MAP kinases may play less significant roles in ESC differentiation than in the regulation of cellular activities of fully differentiated somatic cells...