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Shannon
McKinney-Freeman, Ph.D. Instructor in Pediatrics |
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In 2003, I joined the Daley lab to study
a cell population functionally reminiscent of hematopoietic stem cells
(HSC) that the group had recently engineered from murine embryonic stem
cells (ESC) and to develop novel methods for the derivation of HSC from
ESC. Despite the group’s success in generating ESC-derived
HSC, there was as yet no knowledge of how these cells compared phenotypically
and functionally to bona fide bone marrow HSC. For ESC-derived
HSC to achieve clinical utility, we must have a good understanding of
their biology. The main object of my research has
been the characterization of the phenotype, function, and in vivo
HSC equivalent of the ESC-derived HSC. As they originate from a
developmentally primitive stem cell, I hypothesized that these cells would
represent a developmental intermediate in the hierarchy of HSC maturation.
Indeed, I have since demonstrated that ESC-derived HSC present a cell
surface phenotype akin to embryonic, rather than bone marrow, HSC.
To glean a better understanding of why ESC-derived HSC are developmentally
immature, I am currently comparing the global gene expression profiles
of HSC purified from multiple stages of embryonic development to that
of ESC-derived HSC and bone marrow HSC. I have also contributed
significant effort to other projects focused on the identification of
novel determinants of HSC development both in vivo and from differentiating
ESC.
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