National Institute on Aging
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Intramural
Developmental Genomics and Aging Section
Minoru S.H. Ko, M.D., Ph.D., Chief
Senior Investigator
Overview: The long-term goal is to understand the fundamental mechanisms for the maintenance of self-renewal, immortality, and pluripotency of early mouse embryos and stem cells. Replicative senescence has been an important focus of aging research for many years, though studies have concentrated on the senescence of cells already committed to mortality; here we rather concentrate on the critical distinction between immortal early embryonic cells and mortal differentiating derivative cells. Studies will utilize the potential of a systematic genomic approach - "embryogenomics" - to analyze global gene expression regulations. The approach includes the construction of cDNA libraries from a small number of cells followed by large-scale cDNA sequencing, in situ hybridization to mouse embryonic and fetal preparations, and simultaneous gene expression analyses by DNA chip/microarray technologies. We believe that such global studies will provide greater understanding of mechanisms that will aid in the adaptation of stem cells to replacement therapy for aging and dysfunctional cells and organs. We focus on three complementary research programs.
1. Systematic Analysis of Gene Regulatory Networks
2. Preimplantation Mouse Development
3. Embryonic and Tissue Stem Cells
Selected Recent Publications:
  • Hamatani T et al. (2004). Dynamics of global gene expression changes during mouse preimplantation development. Dev. Cell. 6: 117-131.
  • Ko MSH (2006). Expression profiling of the mouse early embryo: Reflections and perspectives. Dev Dyn. 235: 2437-2448.
  • Falco G et al. (2007). Zscan4: A novel gene expressed exclusively in late 2-cell embryos and embryonic stem cells. Dev Biol. 307: 539-550.
  • Ko MSH (2008). Stem Cell Biology, Chapter 66, Harrison's Principles of Internal Medicine, 17th Edition. (Eds. Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J). McGraw-Hill, NY.
  • Yan Z et al. (2008). BAF250B-associated SWI/SNF chromatin-remodeling complex is required to maintain undifferentiated mouse embryonic stem cells. Stem Cells. 26: 1155-1165.
  • Sharova LV et al. (2008). Database for mRNA half-life of 19977 genes obtained by DNA microarray analysis of pluripotent and differentiating mouse embryonic stem cells. DNA Res. Nov 11.
  • Aiba K et al. (2008). Defining developmental potency and cell lineage trajectories by expression profiling of differentiating mouse embryonic stem cells. In press in DNA Res.
Caption: Principal Component Analysis of DNA microarray data visualized three 'cell lineage trajectories,' which represent the differentiation of ES cells into the first three lineages in mammalian development: primitive endoderm (turquoise arrow), trophoblast (blue arrow), and primitive ectoderm/neural ectoderm (brown arrow). The PCA figure resembles the conceptual picture of Waddington's epigenetic landscape, where cell lineage trajectories represent creodes. (Aiba et al., 2008).
Caption: Principal Component Analysis of DNA microarray data visualized three "cell lineage trajectories," which represent the differentiation of ES cells into the first three lineages in mammalian development: primitive endoderm (turquoise arrow), trophoblast (blue arrow), and primitive ectoderm/neural ectoderm (brown arrow). The PCA figure resembles the conceptual picture of Waddington's epigenetic landscape, where cell lineage trajectories represent creodes. (Aiba et al., 2008).
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Updated: Tuesday December 16, 2008