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Expression profile analysis of aorta-gonad-mesonephros region-derived stromal cells reveals genes that regulate hematopoiesis
Authors:Nagao Kenji  Ohta Takayuki  Hinohara Atsushi  Tahara Tomoyuki  Hagiwara Tetsuya  Maeda Yoshitake  Yoneya Takashi  Sohma Yoshiaki  Heike Toshio  Nakahata Tatsutoshi  Inagaki Yoshimasa  Nishikawa Mitsuo
Institution:a Frontier Laboratory, Kirin Pharma CO., LTD., 3 Miyahara, Takasaki, Gunma 370-1295, Japan
b Discovery Research Laboratories, Kirin Pharma CO., LTD., 3 Miyahara, Takasaki, Gunma 370-1295, Japan
c Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
Abstract:The aorta-gonad-mesonephros (AGM) region is involved in the generation and maintenance of the first definitive hematopoietic stem cells (HSCs). A mouse AGM-derived cell line, AGM-S3, was shown to support the development of HSCs. To elucidate the molecular mechanisms regulating early hematopoiesis, we obtained subclones from AGM-S3, one of which was hematopoiesis supportive (S3-A9) and the other one of which was non-supportive (S3-A7), and we analyzed their gene expression profiles by gene chip analysis. In the present study, we found that Glypican-1 (GPC1) was highly expressed in the supportive subclone AGM-S3-A9. Over-expression of GPC1 in non-supportive cells led to the proliferation of progenitor cells in human cord blood when cocultured with the transfected-stromal cells. Thus, GPC1 may have an important role in the establishment of a microenvironment that supports early events in hematopoiesis.
Keywords:AGM  Stroma  Glypican  Hematopoietic stem cell
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