Stem cells are found as units of organization, generation, and regeneration in virtually all metazoan species. Both germline and somatic tissues are organized in a stem/progenitor/progeny plan of cell lineage development. Hematopoietic stem cells (HSC) are the only functional cells in human bone marrow/mobilized peripheral blood transplantation, and it is likely that other organ and tissue-specific cell therapies will depend on their content of stem cells for their regenerative capacities. We have recently found that in a protochordate species, Botryllus schlosseri, that both germline and somatic cell progenitors-probably stem cells-can migrate between genetically distinct individuals sharing a natural vascular bridge and replace host cells in the generation (or regeneration) of gonads and somatic organs respectively. The predilection to win in these competitions is genetically determined, and therefore stem cells are likely units of natural selection also. Here we embark on a series of experiments to create the assays and the tools (mainly monoclonal antibodies to separate putative stem cells and to characterize their progeny) to isolate each of these Botryllus stem cells. In parallel we plan to define the forms of Mendelian inheritance that characterize somatic and germline cell competitive proclivities. These experiments will serve as a prelude to develop an understanding of the phylogeny of stem cells, the genetic bases for their functions, and the eventual identification of the human homologues of these Botryllus genes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK054762-01A1
Application #
6045985
Study Section
Hematology Subcommittee 2 (HEM)
Program Officer
Badman, David G
Project Start
2000-08-01
Project End
2005-02-28
Budget Start
2000-08-01
Budget End
2001-02-28
Support Year
1
Fiscal Year
2000
Total Cost
$317,498
Indirect Cost
Name
Stanford University
Department
Pathology
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Kassmer, Susannah H; Rodriguez, Delany; Langenbacher, Adam D et al. (2015) Migration of germline progenitor cells is directed by sphingosine-1-phosphate signalling in a basal chordate. Nat Commun 6:8565
Kawamura, Kaz; Tiozzo, Stefano; Manni, Lucia et al. (2011) Germline cell formation and gonad regeneration in solitary and colonial ascidians. Dev Dyn 240:299-308
McKitrick, Tanya R; De Tomaso, Anthony W (2010) Molecular mechanisms of allorecognition in a basal chordate. Semin Immunol 22:34-8
Tiozzo, Stefano; Murray, Maureen; Degnan, Bernard M et al. (2009) Development of the neuromuscular system during asexual propagation in an invertebrate chordate. Dev Dyn 238:2081-94
Voskoboynik, Ayelet; Soen, Yoav; Rinkevich, Yuval et al. (2008) Identification of the endostyle as a stem cell niche in a colonial chordate. Cell Stem Cell 3:456-64
Tiozzo, Stefano; Voskoboynik, Ayelet; Brown, Federico D et al. (2008) A conserved role of the VEGF pathway in angiogenesis of an ectodermally-derived vasculature. Dev Biol 315:243-55
Voskoboynik, Ayelet; Simon-Blecher, Noa; Soen, Yoav et al. (2007) Striving for normality: whole body regeneration through a series of abnormal generations. FASEB J 21:1335-44
Lapidot, Z; Rinkevich, B (2006) Development of monoclonal antibodies specific to urochordate intracellular epitopes. Cell Biol Int 30:190-5
Laird, Diana J; Chang, Wen-Teh; Weissman, Irving L et al. (2005) Identification of a novel gene involved in asexual organogenesis in the budding ascidian Botryllus schlosseri. Dev Dyn 234:997-1005
Lapidot, Ziva; Rinkevich, Baruch (2005) Development of panel of monoclonal antibodies specific to urochordate cell surface antigens. Mar Biotechnol (NY) 7:532-9

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