Glial cell line-derived neurotrophic factor alters the growth characteristics and genomic imprinting of mouse multipotent adult germline stem cells.
This study evaluated the essentiality of glial cell line-derived neurotrophic factor (GDNF) for in vitro culture of established mouse multipotent adult germline stem (maGS) cell lines by culturing them in the presence of GDNF, leukemia inhibitory factor (LIF) or both. We show that, in the absence of LIF, GDNF slows the proliferation of maGS cells and result in smaller sized colonies without any change in distribution of cells to different cell-cycle stages, expression of pluripotency genes and in vitro differentiation potential. Furthermore, in the absence of LIF, GDNF increased the expression of male germ-line genes and repopulated the empty seminiferous tubule of W/W(v) mutant mouse without the formation of teratoma. GDNF also altered the genomic imprinting of Igf2, Peg1, and H19 genes but had no effect on DNA methylation of Oct4, Nanog and Stra8 genes. However, these effects of GDNF were masked in the presence of LIF. GDNF also did not interfere with the multipotency of maGS cells if they are cultured in the presence of LIF. In conclusion, our results suggest that, in the absence of LIF, GDNF alters the growth characteristics of maGS cells and partially impart them some of the germline stem (GS) cell-like characteristics.
Jung
Yoon Hee
YH
Department of Bioscience and Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-Gu, Seoul 143701, South Korea.
Gupta
Mukesh Kumar
MK
Oh
Shin Hye
SH
Uhm
Sang Jun
SJ
Lee
Hoon Taek
HT
D053687:Adult Stem Cells / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape; D018920:Coculture Techniques; D019175:DNA Methylation; D015870:Gene Expression / Q000187:drug effects; D018392:Genomic Imprinting / Q000187:drug effects; D005854:Germ Cells / Q000187:drug effects / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology*; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D039902:Multipotent Stem Cells / Q000187:drug effects / Q000502:physiology; D012671:Seminiferous Tubules / Q000166:cytology / Q000187:drug effects; D033581:Stem Cell Transplantation / Q000009:adverse effects; D013724:Teratoma / Q000473:pathology; D014212:Tretinoin / Q000494:pharmacology
D000970:Antineoplastic Agents; D051100:Glial Cell Line-Derived Neurotrophic Factor; D053605:Leukemia Inhibitory Factor; D014212:Tretinoin