National Institute on Aging
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Research Programs 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: |
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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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