TY - JOUR
T1 - Over expression of NANOS3 and DAZL in human embryonic stem cells
AU - Panula, Sarita
AU - Reda, Ahmed
AU - Stukenborg, Jan Bernd
AU - Ramathal, Cyril
AU - Sukhwani, Meena
AU - Albalushi, Halima
AU - Edsgärd, Daniel
AU - Nakamura, Michiko
AU - Söder, Olle
AU - Orwig, Kyle E.
AU - Yamanaka, Shinya
AU - Reijo Pera, Renee A.
AU - Hovatta, Outi
N1 - Funding Information:
The authors thank the members of the Outi Hovatta laboratory and Dr. Fredrik Lanner for guidance and discussions, Dr. Björn Rozell for assistance in histological analysis, and Dr. Erik Sundström and Dr. Elisabeth Åkesson for fetal tissue samples. The authors would like to acknowledge support from Science for Life Laboratory, the National Genomics Infrastructure (NGI), Sweden, the Knut and Alice Wallenberg Foundation and UPPMAX for providing assistance in massively parallel DNA sequencing and computational infrastructure.
Publisher Copyright:
© 2016 Panula et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/10
Y1 - 2016/10
N2 - The mechanisms underlying human germ cell development are largely unknown, partly due to the scarcity of primordial germ cells and the inaccessibility of the human germline to genetic analysis. Human embryonic stem cells can differentiate to germ cells in vitro and can be genetically modified to study the genetic requirements for germ cell development. Here, we studied NANOS3 and DAZL, which have critical roles in germ cell development in several species, via their over expression in human embryonic stem cells using global transcriptional analysis, in vitro germ cell differentiation, and in vivo germ cell formation assay by xenotransplantation. We found that NANOS3 over expression prolonged pluripotency and delayed differentiation. In addition, we observed a possible connection of NANOS3 with inhibition of apoptosis. For DAZL, our results suggest a post-transcriptional regulation mechanism in hES cells. In addition, we found that DAZL suppressed the translation of OCT4, and affected the transcription of several genes associated with germ cells, cell cycle arrest, and cell migration. Furthermore, DAZL over expressed cells formed spermatogonialike colonies in a rare instance upon xenotransplantation. These data can be used to further elucidate the role of NANOS3 and DAZL in germ cell development both in vitro and in vivo.
AB - The mechanisms underlying human germ cell development are largely unknown, partly due to the scarcity of primordial germ cells and the inaccessibility of the human germline to genetic analysis. Human embryonic stem cells can differentiate to germ cells in vitro and can be genetically modified to study the genetic requirements for germ cell development. Here, we studied NANOS3 and DAZL, which have critical roles in germ cell development in several species, via their over expression in human embryonic stem cells using global transcriptional analysis, in vitro germ cell differentiation, and in vivo germ cell formation assay by xenotransplantation. We found that NANOS3 over expression prolonged pluripotency and delayed differentiation. In addition, we observed a possible connection of NANOS3 with inhibition of apoptosis. For DAZL, our results suggest a post-transcriptional regulation mechanism in hES cells. In addition, we found that DAZL suppressed the translation of OCT4, and affected the transcription of several genes associated with germ cells, cell cycle arrest, and cell migration. Furthermore, DAZL over expressed cells formed spermatogonialike colonies in a rare instance upon xenotransplantation. These data can be used to further elucidate the role of NANOS3 and DAZL in germ cell development both in vitro and in vivo.
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U2 - 10.1371/journal.pone.0165268
DO - 10.1371/journal.pone.0165268
M3 - Article
C2 - 27768780
AN - SCOPUS:84992315330
SN - 1932-6203
VL - 11
JO - PLoS One
JF - PLoS One
IS - 10
M1 - e0165268
ER -