This application is sent in response to the RFA entitled NIDDK Progenitor Cell Genome Projects (RFA-DK-02-027). The Project will coordinate several investigators with expertise in stem cell isolation (Goodell), liver cell biology (Darlington, Weiss), intestinal development (Henning), biostatistics (Shaw), cDNA microarray manufacture and analysis (Darlington, White), gene profiling by a novel sequence based strategy (Gunaratne), and database management and data distribution (Steffen, Shaw). With the exception of Dr. Weiss, these investigators are faculty at Baylor College of Medicine.
The aims of the application are to characterize populations of putative stem cells from the liver, intestine and cells obtained from embryonic liver that are able to be maintained in culture and that show the capacity to differentiate in vitro. Characterization of these cells will be done in five ways; (1) by analysis of known markers that are associated with stem cells in the hematopoietic lineage, (2) by analysis of markers of mature liver or gut cells, (3) by transplantation to the liver using the fumarylacetoacetate hydrolyze (FAH) deficient mouse, (4) by cDNA microarray analysis, and (5) by a sequence based gene profiling approach. The data from these characterizations will be organized and distributed through a web site using software and interfaces that will permit easy access by the research community. Protocols, custom arrays and cell lines will be distributed on request.
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| Chambers, Stuart M; Shaw, Chad A; Gatza, Catherine et al. (2007) Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation. PLoS Biol 5:e201 |
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| Strick-Marchand, Helene; Morosan, Serban; Charneau, Pierre et al. (2004) Bipotential mouse embryonic liver stem cell lines contribute to liver regeneration and differentiate as bile ducts and hepatocytes. Proc Natl Acad Sci U S A 101:8360-5 |
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