THESIS
2017
vii, 65 pages : illustrations (some color) ; 30 cm
Abstract
Vertebrate skeletal muscles possess remarkable regenerative capacity in response to
injury due to the presence of muscle stem cells, also called muscle satellite cells
(MuSC). Adult MuSC are quiescent under normal conditions, but become activated
after injury. Activated satellite cells re-enter the cell cycle to generate a large pool of
myogenic precursor cells (MPCs), and these MPCs will then differentiate and fuse to
form new myofibers.
PAX7 is a well-characterized marker for MuSC and is indispensable for
injury-induced muscle regeneration. However, the exact role of PAX7 remains largely
unknown. PAXBP1 is a novel PAX7-interacting protein identified by our group using
yeast two hybrid screening. In cell culture models, both PAX7 and PAXBP1 are
required for MuSC proliferation...[
Read more ]
Vertebrate skeletal muscles possess remarkable regenerative capacity in response to
injury due to the presence of muscle stem cells, also called muscle satellite cells
(MuSC). Adult MuSC are quiescent under normal conditions, but become activated
after injury. Activated satellite cells re-enter the cell cycle to generate a large pool of
myogenic precursor cells (MPCs), and these MPCs will then differentiate and fuse to
form new myofibers.
PAX7 is a well-characterized marker for MuSC and is indispensable for
injury-induced muscle regeneration. However, the exact role of PAX7 remains largely
unknown. PAXBP1 is a novel PAX7-interacting protein identified by our group using
yeast two hybrid screening. In cell culture models, both PAX7 and PAXBP1 are
required for MuSC proliferation. However, different from PAX7, PAXBP1 also
regulates myoblast differentiation in culture, suggesting PAXBP1 also plays PAX7
independent roles.
To elucidate the roles of PAXBP1 in vivo in adult MuSC, our group generated
inducible MuSC-specific Paxbp1 knockout (KO) mice. Preliminary data showed that
PAXBP1 was not required for MuSC maintenance in uninjured muscles but
indispensable for injury-induced muscle regeneration. Specifically, the quiescent
PAXBP1-null MuSC failed to enter the cell cycle after injury, which resulted in a total
block of injury-induced muscle regeneration. Indeed, RNA-seq data revealed a global
downregulation of positive regulators of the cell cycle in KO cells. Moreover, the
PAXBP1-null MuSC displayed severe morphology and motility defect. Our results
demonstrated that PAXBP1 has crucial functions in adult MuSC in vivo. Next, we
will try to rescue the defects of KO cells using potential PAXBP1 target genes. In
addition, we will look for new PAXBP1 binding partners for better understandings of
the underlying molecular mechanism by which PAXBP1 regulates the cell cycle
re-entry from the quiescent MuSC after injury.
Post a Comment