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Updated: Jul 17, 2026
In Vitro Differentiation of Human Pluripotent Stem Cells into Trophoblastic Cells
Published on: March 16, 2017
Bone morphogenetic proteins induce germ cell differentiation from human embryonic stem cells
Kehkooi Kee1, Joanna M Gonsalves, Amander T Clark
1UCSF 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.
Abstract:
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.
Insights
Recombinant human bone morphogenetic proteins (BMPs) promote human germ cell differentiation from embryonic stem cells. BMP4, BMP7, and BMP8b enhance the expression of germ cell markers, aiding in the development of primordial germ cells.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Reproductive Biology
Background:
- Bone morphogenetic proteins (BMPs) are crucial for primordial germ cell (PGC) specification in mice.
- Human BMP4 has shown potential in promoting PGC differentiation from mouse embryonic stem cells and in organ cultures.
- The role of recombinant human BMPs in inducing germ cell differentiation from human embryonic stem cells (hESCs) requires further investigation.
Purpose of the Study:
- To investigate the potential of recombinant human BMPs (specifically BMP4, BMP7, and BMP8b) to induce germ cell differentiation from hESCs.
- To assess the expression of germ cell-specific markers following BMP treatment during hESC differentiation.
Main Methods:
- Human embryonic stem cells (hESCs) were differentiated into embryoid bodies (EBs).
- Recombinant human BMP4, BMP7, and BMP8b were added to the differentiation media.
- Expression of germ cell-specific markers, VASA and SYCP3, was analyzed.
- The percentage of VASA-positive cells was quantified.
Main Results:
- Recombinant human BMP4 significantly increased the expression of VASA and SYCP3 during hESC differentiation into EBs.
- BMP7 and BMP8b demonstrated additive effects on germ cell induction when used in combination with BMP4.
- BMP treatment led to a higher percentage of VASA-positive cells in differentiating hESCs.
Conclusions:
- Recombinant human BMPs, particularly BMP4, can enhance the differentiation of germ cells from hESCs.
- BMP7 and BMP8b may act synergistically with BMP4 to promote germ cell induction.
- While modest, the effects of BMPs are reproducible and suggest their utility in directed germ cell differentiation protocols.
