研究会のご案内
リエゾンラボ研究会
発表内容

Title:
The roles of Kr u ppel-like factors during early mouse development and the self-renewal of ESCs

Masatsugu Ema
Department of Anatomy and Embryology, Institute of Basic Med. Sci., Tsukuba University

Abstract:
ES (Embryonic Stem) cells are derived from the blastocyst and have the potential to give rise to derivatives of each germ layer. Induced pluripotent stem (iPS) cells can be derived from lineage-restricted cells, such as fibroblasts, by forced expression of specific transcription factors. Although recent studies indicate that Kr u ppel-like factors (Klfs) are essential for both maintenance of ES cell self-renewal and reprogramming of somatic cells into a pluripotent state, the molecular mechanism of these processes remains unknown. Thus, understanding the molecular mechanism of ES cell self-renewal by Klfs would be important for the efficient generation of patient-specific pluripotent stem cells and for the development of regenerative medicine.
By generating Klf5 knock-out and over-expressing ESCs, we have showed that Klf5 suppresses differentiation and promotes proliferation of ESC. On the other hand, Klf4 suppresses differentiation and proliferation, indicating that there are overlapped and non-overlapped functions among Klfs. We also show the differential roles of Klfs on differentiation in ESCs.
On the other hand, we have been investigating the development of the Flk1 (VEGF-R2)-positive mesoderm cells during ESC differentiation and mouse development. Recent our data indicate that VEGF-Flk1 pathway is important for the size determination of multiple mesoderm-derived tissues.

References:
Ema, M, Mori, D, Niwa, H, Hasegawa, Y, Yamanaka, Y, Hitoshi, S, Mimura, J, Kawabe, Y, Hosoya, T, Morita, M, Shimosato, D, Uchida, K , Suzuki, N, Yanagisawa, J, Sogawa, K, Rossant, J, Yamamoto, M, Takahashi, S, and Fujii-Kuriyama, Y. Kruppel-like factor 5 Is Essential For Blastocyst Development and the Normal Self-Renewal of Mouse ES cells. Cell Stem Cell 3:555-567. (2008) .

Ema M, Yokomizo T, Wakamatsu A, Terunuma T, Yamamoto M, Takahashi S. Primitive erythropoiesis from mesodermal precursors expressing VE-cadherin, PECAM-1, Tie2, endoglin, and CD34 in the mouse embryo. (2006). Blood. 108:4018-4024.

Ema M , Takahashi S, Rossant J. Deletion of selection cassette but not cis-acting elements in targeted Flk1-lacZ allele reveals Flk1 expression in multipotent mesodermal progenitors. Blood.107: 111-117. (2006) .

Ema M, Faloon P, Zhang WJ, Hirashima M, Reid T, Stanford WL, Orkin S, Choi K, Rossant J. Combinatorial effects of Flk1 and Tal1 on vascular and hematopoietic development in the mouse. (2003). Genes Dev. 17:380-393.