Modeling Normal and Malignant Hematopoiesis Using Human Pluripotent Stem Cells

Abstract

This thesis outlines progress made in creating several human pluripotent stem cell based models for studying hematopoiesis. Induced pluripotent stem cells were generated from human umbilical cord blood cells selected for the early hematopoietic progenitor marker CD34. Furthermore, reprogramming was attempted on primary leukemia samples to generate an induced pluripotent stem cell line with a genetic background harboring the mutations necessary for malignant hematopoiesis. Strategies for manipulating human embryonic stem cells to either express the bcr-abl oncogene or be deficient in the putative tumor suppressor gene sh2b3 were also developed, both genes of which are linked to the expansion of early hematopoietic progenitors.