Farzaneh Khani1,2, Simin Nafian1,2, Sepideh Mollamohammadi3, Shiva Nemati2, Bahare Shokoohian2, Seyedeh Nafiseh Hassani3, Hossein Baharvand3,4, Hamid Reza Soleimanpour-Lichaei5, Ghasem Hosseini Salekdeh6,7. 1. Department of Stem Cells and Regenerative Medicine, Institute of Medical Biotechnology, National Institute of Genetic Engineering & Biotechnology (NIGEB), P.O.Box: 14965-161, Tehran, Iran. 2. Department of Molecular Systems Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, 16656-59911, Tehran, Iran. 3. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, 16656-59911, Tehran, Iran. 4. Department of Developmental Biology, University of Science and Culture, 13145-871, Tehran, Iran. 5. Department of Stem Cells and Regenerative Medicine, Institute of Medical Biotechnology, National Institute of Genetic Engineering & Biotechnology (NIGEB), P.O.Box: 14965-161, Tehran, Iran. hrs@nigeb.ac.ir. 6. Department of Molecular Systems Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, 16656-59911, Tehran, Iran. hsalekdeh@gmail.com. 7. Department of Molecular Sciences, Macquarie University, Sydney, NSW, Australia. hsalekdeh@gmail.com.
Abstract
BACKGROUND: The human Y chromosome harbors genes that are mainly involved in the growth, development, sexual dimorphism, and spermatogenesis process. Despite many studies, the function of the male-specific region of the Y chromosome (MSY) awaits further clarification, and a cell-based approach can help in this regard. RESULTS: In this study, we have developed four stable transgenic male embryonic stem cell (ESCs) lines that can overexpress male-specific genes HSFY1, RBMY1A1, RPS4Y1, and SRY. As a proof of principle, we differentiated one of these cell lines (RPS4Y1 over-expressing ESCs) to the neural stem cell (rosette structure) and characterized them based on the expression level of lineage markers. RPS4Y1 expression in the Doxycycline-treated group was significantly higher than control groups at transcript and protein levels. Furthermore, we found Doxycycline-treated group had a higher differentiation efficiency than the untreated control groups. CONCLUSIONS: Our results suggest that the RPS4Y1 gene may play a critical role in neurogenesis. Also, the generated transgenic ESC lines can be widely employed in basic and preclinical studies, such as sexual dimorphism of neural and cardiac functions, the development of cancerous and non-cancerous disease models, and drug screening.
BACKGROUND: The human Y chromosome harbors genes that are mainly involved in the growth, development, sexual dimorphism, and spermatogenesis process. Despite many studies, the function of the male-specific region of the Y chromosome (MSY) awaits further clarification, and a cell-based approach can help in this regard. RESULTS: In this study, we have developed four stable transgenic male embryonic stem cell (ESCs) lines that can overexpress male-specific genes HSFY1, RBMY1A1, RPS4Y1, and SRY. As a proof of principle, we differentiated one of these cell lines (RPS4Y1 over-expressing ESCs) to the neural stem cell (rosette structure) and characterized them based on the expression level of lineage markers. RPS4Y1 expression in the Doxycycline-treated group was significantly higher than control groups at transcript and protein levels. Furthermore, we found Doxycycline-treated group had a higher differentiation efficiency than the untreated control groups. CONCLUSIONS: Our results suggest that the RPS4Y1 gene may play a critical role in neurogenesis. Also, the generated transgenic ESC lines can be widely employed in basic and preclinical studies, such as sexual dimorphism of neural and cardiac functions, the development of cancerous and non-cancerous disease models, and drug screening.
Authors: Zohreh Jangravi; Mehdi Alikhani; Babak Arefnezhad; Mehdi Sharifi Tabar; Sara Taleahmad; Razieh Karamzadeh; Mahdieh Jadaliha; Seyed Ahmad Mousavi; Diba Ahmadi Rastegar; Pouria Parsamatin; Haghighat Vakilian; Shahab Mirshahvaladi; Marjan Sabbaghian; Anahita Mohseni Meybodi; Mehdi Mirzaei; Maryam Shahhoseini; Marzieh Ebrahimi; Abbas Piryaei; Ali Akbar Moosavi-Movahedi; Paul A Haynes; Ann K Goodchild; Mohammad Hossein Nasr-Esfahani; Esmaiel Jabbari; Hossein Baharvand; Mohammad Ali Sedighi Gilani; Hamid Gourabi; Ghasem Hosseini Salekdeh Journal: J Proteome Res Date: 2012-12-20 Impact factor: 4.466
Authors: Zohreh Jangravi; Mehdi Sharif Tabar; Mehdi Mirzaei; Pouria Parsamatin; Haghighat Vakilian; Mehdi Alikhani; Mohammad Shabani; Paul A Haynes; Ann K Goodchild; Hamid Gourabi; Hossein Baharvand; Ghasem Hosseini Salekdeh Journal: J Proteome Res Date: 2015-08-10 Impact factor: 4.466
Authors: Daniel W Bellott; Jennifer F Hughes; Helen Skaletsky; Laura G Brown; Tatyana Pyntikova; Ting-Jan Cho; Natalia Koutseva; Sara Zaghlul; Tina Graves; Susie Rock; Colin Kremitzki; Robert S Fulton; Shannon Dugan; Yan Ding; Donna Morton; Ziad Khan; Lora Lewis; Christian Buhay; Qiaoyan Wang; Jennifer Watt; Michael Holder; Sandy Lee; Lynne Nazareth; Jessica Alföldi; Steve Rozen; Donna M Muzny; Wesley C Warren; Richard A Gibbs; Richard K Wilson; David C Page Journal: Nature Date: 2014-04-24 Impact factor: 49.962