Bone morphogenetic proteins induce germ cell differentiation from human embryonic stem cells.
The growth factors bone morphogenetic protein-4 (BMP4), BMP7, and BMP8b are required for specification of primordial germ cells (PGCs) in mice. Disruption of the genes that encode these factors leads to a severe reduction in number, or the complete absence, of PGCs. In addition, several studies have demonstrated that human BMP4 can promote PGC differentiation from mouse embryonic stem (ES) cells and in organ cultures. Here, we sought to determine whether recombinant human BMPs could induce differentiation of germ cells from human (h) ES cells. We found that addition of recombinant human BMP4 increased the expression of the germ cell-specific markers VASA and SYCP3 during differentiation of hES cells to embryoid bodies (EBs). In addition, BMP7 and BMP8b showed additive effects on germ cell induction when added together with BMP4. Finally, we observed that addition of BMPs to differentiating ES cells also increased the percentage of cells that stained positively for VASA. We note that the effects of recombinant BMPs were modest but reproducible and suggest that addition of BMPs to differentiation media increases differentiation of human germ cells from hES cells.
Kee
Kehkooi
K
UCSF Human Embryonic Stem Cell Research Center, Department of Obstetrics, Gynecology & Reproductive Sciences, Institute for Stem Cell and Tissue Biology, University of California at San Francisco, San Francisco, CA 94143, USA.
Gonsalves
Joanna M
JM
Clark
Amander T
AT
Pera
Renee A Reijo
RA
D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology*; D015870:Gene Expression; D005854:Germ Cells / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D051379:Mice; D023421:Models, Animal
C525809:BMP4 protein, human; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins