TY - JOUR
T1 - Y chromosome genes may play roles in the development of neural rosettes from human embryonic stem cells
AU - Khani, Farzaneh
AU - Nafian, Simin
AU - Mollamohammadi, Sepideh
AU - Nemati, Shiva
AU - Shokoohian, Bahare
AU - Hassani, Seyedeh Nafiseh
AU - Baharvand, Hossein
AU - Soleimanpour-lichaei, Hamid Reza
AU - Salekdeh, Ghasem Hosseini
PY - 2022/12
Y1 - 2022/12
N2 - 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. Graphical Abstract: [Figure not available: see fulltext.].
AB - 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. Graphical Abstract: [Figure not available: see fulltext.].
KW - Human Embryonic Stem Cells (hESC)
KW - Neural differentiation
KW - RPS4Y1
KW - Stable cell line
KW - Y-Chromosome Human Proteome Project (Y-HPP)
UR - http://www.scopus.com/inward/record.url?scp=85131309990&partnerID=8YFLogxK
U2 - 10.1007/s12015-022-10392-2
DO - 10.1007/s12015-022-10392-2
M3 - Article
C2 - 35661078
AN - SCOPUS:85131309990
SN - 2629-3269
VL - 18
SP - 3008
EP - 3020
JO - Stem Cell Reviews and Reports
JF - Stem Cell Reviews and Reports
IS - 8
ER -