Pax 7 is Necessary For the Myogenic Specification of CD45+ Stem Cells Reviewed by Heather Hall Research by Patrick Seale, Jeff Ishibashi, Anthony Scime, Michael A. Rudnicki

What are stem cells? Undifferentiated cells that have no specific tissue function Two types of stem cells: –Pluripotent –Multipotent

Background Recent studies have identified adult stem cells in skeletal muscle CD45+ cells were originally purified from uninjured muscle CD45+ and CD45- cells do not form muscle in- vitro when cultured alone When cocultured with myoblasts and in-vivo CD45+ and CD45- cells to form muscle Transcription factor Pax 7 is expressed by satellite cells

Review of Literature Muscle derived CD45+ cells purified from uninjured muscle are uniformly nonmyogenic in vitro and do not form muscle in vivo (Asakura et al. 2002) coculture and in vivo injection experiments indicate that CD45+ SP, as well as CD45- SP, cells possess myogenic potential (McKinney-Freeman et al. 2002)

Review of Literature Recent experiments have established that CD45+ adult stem cells have a normal physiological role in tissue regeneration (Polesskaya et al. 2003) The transcription factor Pax7 is specifically expressed in satellite cells (Seale et al. 2000).

Hypothesis Pax 7 directs myogenic specification of adult stem cells in muscle

Materials and Methods CD45+ cells from uninjured muscles were cultured CD45+ cells from 4 day old injured muscle were cultured Cells from the uninjured muscle were infected with a Pax 7 expressing retrovirus CDSC-LacZ and CDSC-Pax 7 cells were injected into the injured muscle of nude mice

In Vitro Results Cells from uninjured muscles do not produce Pax 7 while cells from injured muscles do When cells were infected with Pax 7 expressing virus they expressed proteins that only injured muscle cells were known to express Exposure to Pax 7 caused the CD45+ cells to differentiate into myotubes

In Vitro Results Pax 7 infected Control

In three separate in vivo experimental trials, the number of regenerated fibers was markedly increased in Ad-Pax 7 treated muscles relative to Ad-LacZ In Vivo Results

Discussion Experiments suggest that a population of CD45+ cells reside in muscle and can form muscle cells Data supports the hypothesis and establishes that Pax 7 is necessary for adult stem cells to become muscle tissue

Future Uses Methods to deliver Pax7 or upregulate its expression in stem cells may be useful in treating degenerative muscle disease.

Work Cited