ISCRM

Germline Stem Cells

Chris T. Amemiya, PhD (Benaroya Research Institute)
In my research lab we are interested in the origins of novelty and innovation in vertebrates, with special emphasis on the adaptive immune system and vertebrate bauplan. We use whatever tools are necessary to address fundamental biological questions, particularly large-insert cloning, comparative genomics, computational biology and developmental biology. Although our research is fundamental in scope, we are always looking for ways in which our findings may be relevant and applicable to biomedical research. Our most recent work focuses on stem cell biology in a nonmammalian vertebrate model system, the sea lamprey. We have discovered that the sea lamprey jettisons roughly 20% of its genome during embryonic development, the deleted DNA encompassing both noncoding as well as coding sequences. This rampant loss of chromatin in all resultant somatic lineages raises several questions with respect to mechanism of loss and, more importantly, to the partitioning of gene functions in germline and somatic lineages and the maintenance of genetic totipotency. This work is interrelated with our research on a rearranging gene system that is involved in adaptive immune recognition in lampreys but also requisite for building the early embryo. We are interested in understanding the role of global genome dynamism described above in the evolution and development of this rearranging gene system.

Daniel G. Miller, MD, PhD (Pediatrics)
Dr. Miller and members of his research group utilize induced pluripotent stem cells (IPSc) made from the skin cells of individuals with Facioscapulohumeral Muscular Dystrophy (FSHD) to understand the etiology of this debilitating condition. The hypothesis is that FSHD is caused by a defect in muscle development and/or maintenance so studying differences between control and patient embryonic cells as they differentiate to form muscle may reveal key mechanisms of disease pathology. Dr. Miller is also interested in treatment strategies for genetic conditions so members of his research group use vectors based on Adeno-Associated Virus (AAV) to perform gene targeting in primary human cells. This approach is currently being applied to keratinocytes from patients affected with a skin blistering condition called Epidermolysis Bullosa. The molecular consequence of disease-causing mutations can also be studied by creating the same mutations in primary human cells, or correcting mutations in cells from affected patients.
Dr. Miller also sees patients with genetic conditions in the pediatric medical genetics clinic at Children’s Hospital.

Hannele Ruohola-Baker, PhD (Biochemistry)
This group has recently shown that Dcr-1-deficient germ line stem cells are delayed in the CDK-inhibitor We p21/p27/Dacapo-dependent G1/S transition, suggesting that miRNAs are required for stem cells to bypass the normal G1/S checkpoint (Hatfield et al., 2005, Nature). Hence, the miRNA pathway might be part of a mechanism that makes stem cells insensitive to environmental signals that normally stop the cell cycle at the G1/S transition. Since miRNAs are a novel class of genes involved in human tumorgenesis, it is tempting to speculate that miRNAs could play a similar role in cancer cells. The investigator is now moving towards analyzing micro RNA function in humans.

Billie Swalla (Biology)
We are studying stem cells in colonial ascidians. In botryllid ascidians, there are multiple stem cells which circulate in the blood. Some stem cells are necessary to form a new individual asexually, and there are also germline stem cells for gametes to develop in the ovary and testes. We are developing molecular markers to identify various stem cells circulating in the colonial ascidians, in order to understand their potential. Brown et al. (2009; Development 136: 3485-3494) has shown that there are germline precursors that are specified early, but then continue to populate gonads as they develop. We have also shown that these colonial ascidians undergo extensive regeneration, thorough activation of a piwi-positive stem cell population (Brown et al. 2009; JEZ:MDE 312B: 885-900).

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