The establishment of human pluripotential stem cell cell lines has led to a resurgence of interest in stem cell biology. This interest is largely due to the therapeutic potential of stem cells for repairing degenerative diseases and injuries. Before recent breakthroughs in studies of human stem cells can be effectively and safely applied in the clinic, many basic questions about the biology of stem cells need to be addressed. These include: how is stem cell proliferation regulated in vivo to generate the appropriate number of daughter stem cells and differentiating progeny without forming tumors? How is the developmental potential of a stem cell restricted to a particular fate? How is pluripotentiality maintained and what steps lead to loss of pluripotentiality? The work proposed here will address these fundamental questions using the freshwater planarian, Schmic/tea mediterranea, as a model organism for studying stem cell regulation. Planarians- classic models of regeneration experiments- can regenerate entire animals from small fragments of their bodies. This remarkable plasticity is based upon a stem cell population present in the adult worm. These stem cells are used both to replace cells lost during the course of cell turnover and to regenerate missing structures when the animal is transected. Recent advances permit this classic system to be re-examined in detail at both cellular and molecular levels. Thus, environmental influences on stem cell proliferation will be studied by analysing cell cycle kinetics in intact and regeneratiing planarians. These experiments will deter- mine if wounding regulates the cell cycle of planarian stem cells. If it does, these experiments will also define the phases of the cell cycle that are regulated, an important consideration for understand- ing the signaling pathways that lead from wounding to proliferation. The development of automated in situ hybridization techniques and the availablility of over 4000 unique planarian cDNAs provide starting material for defining stem cell-specific genes and raising monoclonal antibodies to identify and study stem cells. Finally, functional analysis using double-stranded RNA-mediated genetic inter- ference will be used to identify genes that play critical roles in stern cell regulation.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD043403-05
Application #
7160539
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Coulombe, James N
Project Start
2003-01-09
Project End
2009-07-31
Budget Start
2007-01-01
Budget End
2009-07-31
Support Year
5
Fiscal Year
2007
Total Cost
$254,280
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Anatomy/Cell Biology
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Rouhana, Labib; Tasaki, Junichi; Saberi, Amir et al. (2017) Genetic dissection of the planarian reproductive system through characterization of Schmidtea mediterranea CPEB homologs. Dev Biol 426:43-55
Iyer, Harini; Issigonis, Melanie; Sharma, Prashant P et al. (2016) A premeiotic function for boule in the planarian Schmidtea mediterranea. Proc Natl Acad Sci U S A 113:E3509-18
Iyer, Harini; Collins 3rd, James J; Newmark, Phillip A (2016) NF-YB Regulates Spermatogonial Stem Cell Self-Renewal and Proliferation in the Planarian Schmidtea mediterranea. PLoS Genet 12:e1006109
Saberi, Amir; Jamal, Ayana; Beets, Isabel et al. (2016) GPCRs Direct Germline Development and Somatic Gonad Function in Planarians. PLoS Biol 14:e1002457
Ong, Ta-Hsuan; Romanova, Elena V; Roberts-Galbraith, Rachel H et al. (2016) Mass Spectrometry Imaging and Identification of Peptides Associated with Cephalic Ganglia Regeneration in Schmidtea mediterranea. J Biol Chem 291:8109-20
Forsthoefel, David J; Waters, Forrest A; Newmark, Phillip A (2014) Generation of cell type-specific monoclonal antibodies for the planarian and optimization of sample processing for immunolabeling. BMC Dev Biol 14:45
Tharp, Marla E; Collins 3rd, James J; Newmark, Phillip A (2014) A lophotrochozoan-specific nuclear hormone receptor is required for reproductive system development in the planarian. Dev Biol 396:150-7
Rouhana, Labib; Weiss, Jennifer A; King, Ryan S et al. (2014) PIWI homologs mediate histone H4 mRNA localization to planarian chromatoid bodies. Development 141:2592-601
Brubacher, John L; Vieira, Ana P; Newmark, Phillip A (2014) Preparation of the planarian Schmidtea mediterranea for high-resolution histology and transmission electron microscopy. Nat Protoc 9:661-73
Rouhana, Labib; Weiss, Jennifer A; Forsthoefel, David J et al. (2013) RNA interference by feeding in vitro-synthesized double-stranded RNA to planarians: methodology and dynamics. Dev Dyn 242:718-30

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