Identification of Novel Mutations in Amniotic Fluid Derived Stem Cells Collected from the Mothers Having Case of Neural Tube Defects
International Journal of Genetics and Genomics
Volume 4, Issue 3, June 2016, Pages: 16-19
Received: Mar. 15, 2016;
Accepted: Apr. 11, 2016;
Published: May 27, 2016
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Ajit Kumar Saxena, Department of Pathology/Laboratory Medicine, All India Institute of Medical Sciences, Patna, Bihar, India
Madhu Jain, Department of Obstetrics and Gynecology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
Meenakshi Tiwari, Department of Pathology/Laboratory Medicine, All India Institute of Medical Sciences, Patna, Bihar, India
Ramanuj Kumar Gupta, Department of Pathology/Laboratory Medicine, All India Institute of Medical Sciences, Patna, Bihar, India
Neural tube defects (NTDs) are severe congenital malformations of central nervous system that have high prevalence with severe consequences. The etiology of NTDs involves interactions of both genetic and epigenetic factors and their complex interactions with stems cells during organogenesis. Despite of recent advances, there has been limited progress in delineating the molecular basis of NTDs that can pave way for prevention, diagnostics and therapeutics. We have previously identified a role for stem cell markers Oct 4, Sox 2 and Nanog 3 in neural tube defect affected pregnancies. In the present report we identified mutations in stem cell pluripotency markers from amniotic fluid derived stem cells isolated from women with NTD affected pregnancy. Oct 4 and Nanog 3 were studied to find a correlation with the disease and its severity. Interestingly, sequence based DNA analysis revealed two different forms of nucleotide changes that were observed in different clinical conditions of NTDs. The mutation in Oct 4 at position 183 G →T and in the sequence of Nanog 3 at 63CAAAAA ACA72 to 38ACAGTCTCT47 appears in the cases of anencephaly and meningomyelocele respectively in comparison to control. These findings suggest that these mutational spectra might be responsible for the alterations in the developmental process during embryogenesis leading to NTDs.
Ajit Kumar Saxena,
Ramanuj Kumar Gupta,
Identification of Novel Mutations in Amniotic Fluid Derived Stem Cells Collected from the Mothers Having Case of Neural Tube Defects, International Journal of Genetics and Genomics.
Vol. 4, No. 3,
2016, pp. 16-19.
Finnell, R. H., Junker, W. M., Wadman, L. K. and Cabrera, R. M. (2002). Gene expression profiling within the developing neural tube. Neurochem. Res. 27: 1165-1180.
Cabrera, R. M., Hill, D. S, Etheredge, A. J. and Finnell, R. H. (2004). Investigations into the etiology of neural tube defects. Birth Defects Res. C. Embryo Today 72: 330-344.
Detrait, E. R., George, T. M., Etchevers, H. C., Gilbert, J. R., et. al. (2005). Human neural tube defects: developmental biology, epidemiology, and genetics. Neurotoxicol. Teratol. 27: 515-524.
Beaudin, A. E. and Stover, P. J. (2009). Insights into metabolic mechanisms underlying folate-responsive neural tube defects: a minireview. Birth Defects Res. A Clin. Mol. Teratol. 85: 274-284.
Motohashi, T., Aoki, H., Chiba, K., Yoshimura, N., et al. (2007). Multipotent cell fate of neural crest-like cells derived from embryonic stem cells. Stem Cells 25: 402-410.
Wang, Z., Oron, E., Nelson, B., Razis, S., Ivanova, N. (2012). Distinct lineage specification roles for NANOG, OCT4, and SOX2 in human embryonic stem cells. Cell Stem Cell 10: 440-54.
Kumar, V., Singh, A., Sharma, S. P., Srivastava, A., Saxena, A., Gangopadhyay, A. N. (2012). Clinical spectrum of neural tube defects with special reference to karyotyping study. J. Pediatr. Neurosci. 7: 82-4.
Saxena, A. K., Pandey, S., Pandey, L. K. (2013). Genetic diversity of stem cells and their functional impact on the development of neural tube defects in Eastern population of India. Genet. Mol. Res. 15: 2380-90.
Wu, G. and Schöler, H. R. Role of Oct 4 in the early embryo development (2014). Cell Regen (Lond). 29: 3 (1): 7.
Guseva, D., Rizvanov, A. A., Salafutdinov, I. I., Kudryashova, N. V. et. al. (2014) Over-expression of Oct 4 and Sox 2 transcription factors enhances differentiation of human umbilical cord blood cells in vivo. Biochem Biophys Res Commun. 451: 503-9.
De Veale, B., Brokhman, I, Mohseni, P., Babak, T., et. al.. (2013) Oct 4 is required ~E7.5 for proliferation in the primitive streak. PLoS Genet.; 9 (11): e1003957.
Chambners, I., Colby, D., Robertson, M., Nochols, J, Lee. S, Tweedie. S, and Smith, A., 2003. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113: 643-655.
Meinhardt, A., Eberle, D., Tazaki, A., Ranga, A., et. al. (2014) 3D reconstitution of the patterned neural tube from embryonic stem cells. Stem Cell Reports 6: 987-99.
Zbinden, M., Duquet, A., Lorente-Trigos, A., Ngwabyt, S. N., Borges, I., Ruiz, i. Altaba, A. (2010). NANOG regulates glioma stem cells and is essential in vivo acting in a cross-functional network with GLI1 and p53. EMBO. J. 4: 2659-74.