Korean J Obstet Gynecol.  2005 Nov;48(11):2618-2626.

The effects of BMP4 and BMP2 on Expression of Trophoblast-Specific Genes in Human Embryonic Stem Cells using SNU-hES3 cell line

• Lee YU
• Lee YK
• Lee JE
• Jang YK
• Hwang JH

Abstract

OBJECTIVE
Human embryonic stem cell derived from blastocyst randomly differentiates into multiple cell types during embryoid body development. Bone morphogenetic proteins (BMPs) are members of the transforming growth factor type beta superfamily. We have a question whether BMP2 and/or BMP4 can induce trophoblast specific genes in human ES cells using SNU hES3 cell line.
METHODS
Human embryonic stem cell line (SNU hES3) was supplied by Miz Medi Hospital Seoul National University. Cultured hES cells were divided into small clumps and then allow for EB formation in differentiation medium. After EB formation, EBs were transferred onto gelatin coated dishes and given hES conditioned medium alone (control) or supplemented as following treatment for 6 days; rhBMP4 100 ng/mL; rhBMP2 100 ng/mL; BMP4 100 ng/mL +BMP2 100 ng/mL. RT PCR was performed for trophoblast specific genes. During culture, supernatant was collected and measured for estradiol (E2), progesterone, and hCG beta by enzymeimmuno assay (EIA) kit.
RESULTS
BMP4 and BMP2 increase chorionic gonadotropin beta (hCG beta), glical cell missing 1 (GMC1), and CD9 as trophoblast specific gene markers confirmed by RT PCR. However, the non classical HLA class I molecule HLAG1, was not expressed in our studies. And we cannot find significant differences of the level of estradiol, hCG nd progesterone in this study.
CONCLUSION
The results suggest that BMP 4 and 2 have an additive effect on induction of trophoblast related genes in SNU hES3 cell line. Although we failed to induce the differentiation of human ES cells to trophoblast, this study could provide the possibility for the differentiation of early human trophoblast cells and thus need further studies.

Keyword

Human embryonic stem cells (SNU hES cell line); BMP4; BMP2; Trophoblast specific gene

MeSH Terms

Blastocyst
Bone Morphogenetic Proteins
Cell Line*
Chorionic Gonadotropin
Chorionic Gonadotropin, beta Subunit, Human
Culture Media, Conditioned
Embryoid Bodies
Embryonic Stem Cells*
Estradiol
Gelatin
Humans*
Polymerase Chain Reaction
Progesterone
Seoul
Transforming Growth Factors
Trophoblasts
Bone Morphogenetic Proteins
Chorionic Gonadotropin
Chorionic Gonadotropin, beta Subunit, Human
Culture Media, Conditioned
Estradiol
Gelatin
Progesterone
Transforming Growth Factors