The goal of this research program is to identify the mechanisms that allow hematopoietic stem cells (HSC) to differentiate into hepatocytes. The project detailed in this proposal is based on a mouse model for liver regeneration. Specifically we propose: 1) To test whether a single, highly purified HSC can differentiate into both the hematopoietic and hepatic lineage. 2) To conduct comparative studies between highly purified HSC from different sources with the aim of defining the best source of HSC for hepatic engraftment. 3) To examine whether hematopoietic engraftment is an obligatory step for hepatocyte differentiation. 4) Characterization of a transitional intermediate cell between HSC and hepatocytes. 5) To test whether HSC can contribute to other non-hematopoietic tissues. 6) To test whether human HSC can differentiate into hepatocytes. These discoveries together enable the identification of key factors for HSC plasticity. We propose that HSC-derived hepatocytes could be the basis for the development of cell-based therapeutics addressing a myriad of devastating human liver diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
7R01DK061843-03
Application #
6662013
Study Section
Special Emphasis Panel (ZHL1-CSR-J (S4))
Program Officer
Badman, David G
Project Start
2001-09-30
Project End
2005-05-31
Budget Start
2003-08-01
Budget End
2004-05-31
Support Year
3
Fiscal Year
2003
Total Cost
$272,700
Indirect Cost
Name
Palo Alto Institute for Research & Edu, Inc.
Department
Type
DUNS #
624218814
City
Palo Alto
State
CA
Country
United States
Zip Code
94304