PSI-25 Effects of restricted maternal nutrition and realimentation during gestation on the fetal progenitor cell population in semitendinosus muscle of sheep

Abstract Satellite cells are muscle stem cells that contribute to postnatal growth. The satellite cell population is established during fetal muscle development, through the retention of Pax7-expressing myogenic progenitor cells. We hypothesized that realimentation during late gestation would ameliorate the negative effect of poor maternal nutrition during mid-gestation on the fetal myogenic progenitor cell population. To test this hypothesis, 47 ewes pregnant with singletons were fed a control diet of 100% of National Research Council (NRC) requirements (CON) starting at day 25 of gestation. At day 50 of gestation, six ewes were euthanized and the remainder were randomly assigned to one of two diets: CON or 60% of CON (RES). On day 90 of gestation, a subset of ewes were euthanized (n = 7 per treatment) and fetal semitendinosus samples were collected. The remaining ewes were maintained on the current diet (CON-CON, RES-RES) or switched to the alternative diet (CON-RES, RES-CON). On day 130 of gestation, all ewes were euthanized for fetal sample collection (n = 6–7 per treatment). Fetal semitendinosus was cryosectioned and immunostained for detection of Pax7(+) cells followed by image analysis. Data were analyzed using the MIXED procedure in SAS. Semitendinosus from RES lambs had a greater number of Pax7(+) cells but similar total cell numbers to CON offspring, resulting in a greater percentage of Pax7(+) cells at d90 of gestation (CON: 13.22 ± 0.74%; RES: 16.01 ± 0.74%, P = 0.01). At day 130, there was no difference in the percentage of Pax7(+) cells between dietary treatment groups (CON-CON: 7.88 ± 0.80%; CON-RES: 6.34 ± 0.74%; RES-RES: 7.82 ± 0.74%; RES-CON: 6.87 ± 0.74%; P > 0.17). The percentage of Pax7(+) cells decreased from day 90 to day 130, regardless of dietary treatment (P < 0.0001). In summary, restricted maternal nutrition may delay progenitor cell differentiation at mid-gestation.

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Rad is temporally regulated within myogenic progenitor cells during skeletal muscle regeneration

AJP Cell Physiology ◽

10.1152/ajpcell.00270.2005 ◽

2006 ◽

Vol 290 (2) ◽

pp. C379-C387 ◽

Cited By ~ 26

Author(s):

Thomas J. Hawke ◽

Shane B. Kanatous ◽

Cindy M. Martin ◽

Sean C. Goetsch ◽

Daniel J. Garry

Keyword(s):

Skeletal Muscle ◽

Progenitor Cells ◽

Cell Population ◽

Muscle Regeneration ◽

Progenitor Cell ◽

Transcriptional Activity ◽

Skeletal Muscle Regeneration ◽

Progenitor Cell Population ◽

Myogenic Progenitor Cells ◽

Myogenic Progenitor

The successful use of myogenic progenitor cells for therapeutic applications requires an understanding of the intrinsic and extrinsic cues involved in their regulation. Herein we demonstrate the expression pattern and transcriptional regulation of Rad, a prototypical member of a family of novel Ras-related GTPases, during mammalian development and skeletal muscle regeneration. Rad was identified using microarray analysis, which revealed robust upregulation of its expression during skeletal muscle regeneration. Our current findings demonstrate negligible Rad expression with resting adult skeletal muscle; however, after muscle injury, Rad is expressed within the myogenic progenitor cell population. Rad expression is significantly increased and localized to the myogenic progenitor cell population during the early phases of regeneration and within the newly regenerated myofibers during the later phases of regeneration. Immunohistochemical analysis demonstrated that Rad and MyoD are coexpressed within the myogenic progenitor cell population of regenerating skeletal muscle. This expression profile of Rad during skeletal muscle regeneration is consistent with the proposed roles for Rad in the inhibition of L-type Ca2+channel activity and the inhibition of Rho/RhoA kinase activity. We also have demonstrated that known myogenic transcription factors (MEF2, MyoD, and Myf-5) can increase the transcriptional activity of the Rad promoter and that this ability is significantly enhanced by the presence of the Ca2+-dependent phosphatase calcineurin. Furthermore, this enhanced transcriptional activity appears to be dependent on the presence of a conserved NFAT binding motif within the Rad promoter. Taken together, these data define Rad as a novel factor within the myogenic progenitor cells of skeletal muscle and identify key regulators of its transcriptional activity.

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