Cellular and Molecular Medicine
Overview
Our research interests mainly focus on two themes.
The first is the reconstitution of the developmental potential with stem cells alone.
We aim to artificially reconstitute mammalian early embryos by using a combination of embryonic stem cells, trophoblast stem cells, and our own proprietary primitive endoderm stem cells.
The second is the epigenetic regulation of organ development and stem cell functions, mediated by Polycomb group (PcG) proteins and DNA methylation (5mC) mechanisms.
Professor:
Haruhiko Koseki, M.D., Ph.D.
TEL: +81-43-226-2187
e-mail: hkoseki●chiba-u.jp
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Research & Education
1. Reconstitution of the developmental potential with stem cells alone
The mammalian blastocyst consists of dozens cells of three distinct cell lineages: epiblast, trophoblast (TB), and primitive endoderm (PrE) and derives all embryonic and extraembryonic tissues. Epiblast, TB, and PrE are the major components of the embryo, placenta, and yolk sac, respectively. ESCs (Evans & Kaufman, Nature (1998)) and TSCs (Tanaka et al, Science (2003)) retain the functional properties of preimplantation epiblast and TB, respectively, We recently succeed to establish fully potent PrE stem cells (PrESCs). We are trying to reconstitute developmental potential by using these stem cells in vitro an to elucidate mechanisms of early embryonic development.
2-1. Epigenetic transcriptional regulatory mechanism led by Polycomb repressive complex (PRC)
We are trying to explore for novel molecules that regulate ncPRC1 binding in CpG sequences and new factors that promote cPRC1 enrichment, which occurs in conjunction with PRC2 accumulation.
2-2. Epigenetic transcriptional regulatory mechanism led by DNA methylation-related factors
We are also working on functional analysis of DNA methylation-related factors (NP95/UHRF1, DNMT1, etc.).
Recent Publications
- Yasuhide Ohinata, Takaho A. Endo, Hiroki Sugishita, Takashi Watanabe, Yusuke Iizuka, Yurie Kawamoto, Atsunori Saraya, Mami Kumon, Yoko Koseki,Takashi Kondo, Osamu Ohara, Haruhiko Koseki. Establishment of mouse stem cells that canrecapitulate the developmental potentialof primitive endoderm. Science. Feb 4. 375: 574-578
- Takada Y, Yaman-Deveci R, Shirakawa T, Sharif J, Tomizawa SI, Miura F, Ito T, Ono M, Nakajima K, Koseki Y, Shiotani F, Ishiguro KI, Ohbo K, Koseki H. Maintenance DNA methylation in pre-meiotic germ cells regulates meiotic prophase by facilitating homologous chromosome pairing. Development. 2021 May 15
- Hiroki Sugishita, Takashi Kondo, Shinsuke Ito, Manabu Nakayama, Nayuta Yakushiji-Kaminatsui, Eiryo Kawakami, Yoko Koseki, Yasuhide Ohinata, Jafar Sharif, Mio Harachi, Neil P. Blackledge, Robert J. Klose and Haruhiko Koseki. Variant PCGF1-PRC1 links PRC2 recruitment with differentiation-associated transcriptional inactivation at target genes. Nature Communications. 2021 September 09