| Developmental Genomics and Aging Section |
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Minoru S.H. Ko, M.D., Ph.D., Chief
Senior Investigator |
| 3. Embryonic and Adult Stem Cells |
| Embryonic stem cells are derived from the inner cell mass (ICM) of the blastocyst and are pluripotent, i.e., give rise to all fetal tissues, including germ lines, in vivo and in vitro. The ES cells have also a capacity called self-renewal, i.e., undergoing an unlimited number of symmetrical divisions without differentiation. Thus, they are naturally immortalized cells with stable and normal karyotypes. Since the first establishment of mouse ES cell lines, these two features have been used to manipulate the mouse genome for the functional studies of genes. The embryonic germ (EG) cells that have similar characteristics have also been derived from mouse primordial germ cells. Recent establishment of human ES and EG cells increases excitement about the possibility of using these embryonic stem cells for therapeutic purposes. For such applications, it is paramount to understand how the ES cells maintain their pluripotency and self-renewal, and how the ES cells differentiate into specific cell lineages in vitro. |
| As a first step to delineate the pathways involved in pluripotency and self-renewal of mouse embryonic stem (ES) cells, we have been examining global changes of gene expression patterns in ES cells during differentiation using the cDNA microarray containing ~15,000 distinct mouse genes. |
| In another approach, we have started from the question: Does any group of genes make stem cells stem cells? In another word, can we find a group of genes that makes committed cells become pluripotent and self-renewing embryonic stem cells? To gain some insight into this problem, we have obtained RNAs from a variety of stem cells in collaboration with experts in the field and have done large-scale gene expression profiling with the NIA 15K mouse cDNA microarrays. We would like to emphasize that at present this microarray is well adapted to this experiment, because the array contains genes that are expressed in early mouse embryos and stem cells. We have thus far conducted expression profiling of the following stem cells: Embryonic stem (ES) cells, Trophoblast stem (TS) cells, Mesenchymal stem (MS) cells, Neural stem (NS) cells, Hematopoietic stem (HS) cells, Embryonic germ (EG) cells. Initial goals will be to identify genes that are commonly expressed in all the stem cells and genes that are uniquely expressed in individual stem cell systems. |
