Abstract:
:Embryonic stem (ES) cells give rise to mesodermal progenitors that differentiate to hematopoietic and cardiovascular cells. The wnt signaling pathway plays multiple roles in cardiovascular development through a network of intracellular effectors. To monitor global changes in wnt signaling during ES cell differentiation, we generated independent ES cell lines carrying the luciferase gene under promoters that uniquely respond to specific wnt pathway branches. Our results show that successive, mutually exclusive waves of noncanonical and canonical wnt signaling precede mesoderm differentiation. Blocking the initial noncanonical JNK/AP-1 signaling with SP60125 aborts cardiovascular differentiation and promotes hematopoiesis, whereas interference with the subsequent peak of canonical wnt signaling using Dkk1 has the opposite effect. Dkk1 blockade triggers counter mechanisms that lead to delayed and extended activation of canonical wnt signaling and mesoderm differentiation that appear to favor the cardiomyocytic lineage at the expense of hematopoietic cells. The cardiomyocytic yield can be further enhanced by overexpression of Wnt11 leading to approximately 95-fold enrichment in contracting cells. Our results suggest that the initial noncanonical wnt signaling is necessary for subsequent activation of canonical signaling and that the latter operates under a regulatory loop which responds to suppression with hyperactivation of compensatory mechanisms. This model provides new insights on wnt signaling during ES cell differentiation and points to a method to induce cardiomyocytic differentiation without precise timing of wnt signaling manipulation. Taking into account the heterogeneity of pluripotent cells, these findings might present an advantage to enhance the cardiogenic potential of stem cells.
journal_name
Stem Cells Devjournal_title
Stem cells and developmentauthors
Rai M,Walthall JM,Hu J,Hatzopoulos AKdoi
10.1089/scd.2011.0326subject
Has Abstractpub_date
2012-01-01 00:00:00pages
54-66issue
1eissn
1547-3287issn
1557-8534journal_volume
21pub_type
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journal_title:Stem cells and development
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pub_type: 杂志文章,评审
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journal_title:Stem cells and development
pub_type: 杂志文章,评审
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journal_title:Stem cells and development
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journal_title:Stem cells and development
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journal_title:Stem cells and development
pub_type: 杂志文章
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更新日期:2020-02-01 00:00:00
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journal_title:Stem cells and development
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journal_title:Stem cells and development
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更新日期:2010-06-01 00:00:00
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journal_title:Stem cells and development
pub_type: 杂志文章
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更新日期:2005-12-01 00:00:00
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journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0509
更新日期:2015-08-01 00:00:00
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journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2016.0054
更新日期:2016-06-01 00:00:00
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journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0243
更新日期:2015-03-01 00:00:00
abstract::Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been used extensively in cancer therapy. However, more than half of glioblastoma multiforme are insensitive to the apoptotic effect of TRAIL. Improvement in therapeutic modalities that enhances the efficacy of TRAIL in glioma is much sought after. In ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0529
更新日期:2013-07-01 00:00:00
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journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0186
更新日期:2010-02-01 00:00:00
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journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0499
更新日期:2010-11-01 00:00:00
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journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2011.0280
更新日期:2012-05-20 00:00:00
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journal_title:Stem cells and development
pub_type: 杂志文章
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journal_title:Stem cells and development
pub_type: 杂志文章
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journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0650
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journal_title:Stem cells and development
pub_type: 杂志文章,评审
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journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0266
更新日期:2014-01-01 00:00:00
abstract::Mesenchymal stromal cells (MSCs) are multipotent stem cells with immunosuppressive and trophic support functions. While MSCs from different sources frequently display a similar appearance in culture, they often show differences in their surface marker and gene expression profiles. Although bone marrow is considered th...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2017.0029
更新日期:2018-01-15 00:00:00
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journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2010.0223
更新日期:2011-01-01 00:00:00
abstract::Human embryonic stem cells (hESCs) exhibiting skewed X chromosome inactivation (XCI) have been reported. The copy number variations (CNVs), loss of heterozygosity (LOH), or single-nucleotide variant (SNV) events in those epigenetically distinct cells remain unknown, and whether such genetic abnormalities will influenc...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0463
更新日期:2015-08-01 00:00:00
abstract::Human embryonic stem (HUES) cells are derived from early individual embryos with unique genetic printing. However, how their epigenetic status might affect their potential to differentiate toward specific lineages remains a puzzling question. Using chromatin immunoprecipitation (ChIP)-polymerase chain reaction and ChI...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0345
更新日期:2015-02-01 00:00:00
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journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2015.0081
更新日期:2015-10-15 00:00:00
abstract::The projected annual demand for stem cell-based dental treatments in the United States can range from over 290 million tooth restorative treatments to 30,000 patients requiring tissue regeneration following craniofacial cancer surgery. Professional dental treatments cost Americans over $60 billion per year. Scientific...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
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更新日期:2006-12-01 00:00:00
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journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0057
更新日期:2013-11-15 00:00:00