THE GENERATION OF FETAL LIVER HEMATOPOIETIC PROGENITOR CELLS: A MODEL SYSTEM TO STUDY HEMATOPOIESIS IN LETHAL GENE DELETIONS
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Date
2000-11
Department
Hood College Biology
Program
Biomedical and Environmental Science
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Abstract
Recent discoveries in hematopoiesis have shed light on the process of
development of mature blood lineages, but still many aspects of lineage
commitment are unknown. Due to the rarity of hematopoietic stem cells (HSCs)
in vivo, it is difficult to purify and sustain cultures of HSCs in vitro.
The Erythroid-Myeloid-Lymphoid (EML) cell line is a primitive HSC cell line
that was immortalized by infecting bone marrow from mice previously treated
with 5 fluorouracil (5-FU) (increases progenitor cell cycling) with a retrovirus
containing a dominant negative retinoic acid receptor a (dnRARa). This cell line
has the phenotype of a primitive hematopoietic progenitor and has been used as
a cell model for the study of hematopoiesis. The protocol to develop EML-like
HSC lines cannot be used to derive HSC lines from mice that, as a consequence
of gene ablation, do not survive after birth. Since the fetal liver is the main area
of embryonic hematopoietic development in the mouse, I have hypothesized that
fetal liver HSCs could be immortalized using the dnRARa containing retrovirus.
Testing the hypothesis has indicated that EML-like cell lines can be
established using murine fetal liver as a source of stem/progenitor cells. Studies
examining morphology, antigen expression, proliferation, and neutrophil
differentiation have illustrated that fetal liver hematopoietic progenitor (FLHP) cell
lines derived from both wild type and CCAAT enhancer binding protein deleted
mice are comparable to their 5-FU treated bone marrow derived EML
counterparts.