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Alejandro Tamez, Guillermo Guerrero-Ramirez, Victor Treviño, Jezreel Pantaleon-Garcia, Judith Zavala, Jorge E Valdez; Expression profiling of stem cell for differentiation into corneal endothelium. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1466.
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© ARVO (1962-2015); The Authors (2016-present)
Tissue engineering attempts to develop corneal alternatives for today's transplant demand has been limited by poor biocompatibility and viability. Although differentiation from limbal stem cells is a plausible alternative, these are scarce and difficult to obtain. Here, we explore the capability of more accessible stem cells from adipose, bone marrow and dental pulp tissue for transdifferentiation by comparing their genetic profiles with corneal endothelial cells through microarray data analysis.
Microarray datasets were obtained from GEO Database: 11 for corneal endothelial cells (HCECs), 3 for adipose derived stem cells (ADSCs), 4 for dental pulp stem cells (DPSCs), and 6 for hematopoietic stem cells (HSCs). After quantile normalization, multiple comparison t-test analysis was made against HCECs to obtain differential gene expression information. Target genes were screened through an adjusted False Discovery Rate (FDR), and an over-representation analysis was made with DAVID Bioinformatics Database to know related pathways, gene ontology and transcription factors.
Out of 47,000 possible genetic transcripts, 829 were differentially expressed in HSCs (p<1E-07), 1944 in ADSCs (p<1E-07), and 2781 in DPSCs (p<1E-07) when compared with HCECs. Over-representation analysis of transcripts showed that: HSCs differ in SRP-dependent cotranslational protein targeting (p=1.15E-31, n=42), viral transcription (p=4.11E-28, n=42), and nuclear-transcribed mRNA catabolic process (p=6.19E-27, n=42) genes; ADSCs differ in Homeobox (p=4.27E-05, n=45), DNA-binding (p=1.01E-04, n=35), and Membrane-related (p=1.67E-04, n=740) probes; and DPSCs differs in nucleotide-binding (p=8.71E-06, n=290) genes, ATP-binding (p=1.64E-04, n=224) and cell-cell adherens junction (p=5.14E-04, n=65) genes.
Differential genetic profiles set the baseline that HSCs are suitable stem cell lineages to be applied in a transdifferentiation protocol to corneal endothelial cells. Nevertheless, additional experimental validations is required to best elucidate a new proposal against an increasing demand of corneal tissue for transplant.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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