Journal
CELL TRANSPLANTATION
Volume 22, Issue 10, Pages 1883-1900Publisher
SAGE PUBLICATIONS INC
DOI: 10.3727/096368912X662444
Keywords
Stemness genes; Early cardiac transcription factors; Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs); Human embryonic stem cells (hESCs)
Funding
- National Advanced Technology Development Plan of China (863 plan) [2006AA02Z469, 2011AA020109]
- National Natural Science Foundation of China [81170094]
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At present, there are still significant barriers that impede the clinical use of hESCs and iPS cells, including ethics, immunorejection, tumorigenesis from hESCs, and teratoma formation from iPS cells. It is therefore necessary to search for alternative sources of stem cells. WJ-MSCs originate from embryonic epiblasts and possess properties intermediate between hESCs and adult stem cells. However, the sternness properties of molecules in WJ-MSCs remain unclear compared to those of hESCs. In the present study, we isolated WJ-MSCs by a nonenzymatic method. Further, using microarray analysis by Affymetrix GeneChip and functional network analyses, we determined the degree of expression of sternness genes exhibited by the Human Stem Cell Pluripotency array. We also defined a wide range of stem cell gene expression in the WJ-MSCs in comparison with hESCs. At the same time, the definitive markers of early cardiac precursor cells and more committed progenitors were further characterized in WJ-MSCs. Our results demonstrated for the first time that WJ-MSCs had significant expression of undifferentiated human embryonic stem cell core markers, such as SOX2, NANOG, LIN28, SSEA1, SSEA3, SSEA4, KLF4, c-MYC, CRIPTO, and REX1, with a relatively lower level of expression than in hESCs. We also found WJ-MSCs have high expression of early cardiac transcription factors, such as Flk-1, Isl-1, and Nkx2.5. Functional analysis revealed signature genes of WJ-MSCs with specific roles involved in immune, cytoskeletal, and chemokine regulation, cell adhesion, and cell signaling. Our study indicated that there is a significant overlap between the sternness genes expressed by hESCs and WJ-MSCs. WJ-MSCs harbor a true stem cell population and are promising cells for stem cell-based therapies.
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