Biomedical subjects

Charlotte A Collins

Publications and source records attributed to Charlotte A Collins.

6 recordsLinked to original sources

PubMed2007

A population of myogenic stem cells that survives skeletal muscle aging.

Age-related decline in integrity and function of differentiated adult tissues is widely attributed to reduction in number or regenerative potential of resident stem cells. The satellite cell, resident beneath the basal lamina of skeletal muscle myofibers, is the principal myogenic stem cell. Here we have explored the capacity of satellite cells within aged mouse muscle to regenerate skeletal muscle and to self-renew using isolated myofibers in tissue culture and in vivo. Satellite cells expressing Pax7 were depleted from aged muscles, and when aged myofibers were placed in culture, satellite cell myogenic progression resulted in apoptosis and fewer total differentiated progeny. However, a minority of cultured aged satellite cells generated large clusters of progeny containing both differentiated cells and new cells of a quiescent satellite-cell-like phenotype characteristic of self-renewal. Parallel in vivo engraftment assays showed that, despite the reduction in Pax7(+) cells, the satellite cell population associated with individual aged myofibers could regenerate muscle and self-renew as effectively as the larger population of satellite cells associated with young myofibers. We conclude that a minority of satellite cells is responsible for adult muscle regeneration, and that these stem cells survive the effects of aging to retain their intrinsic potential throughout life. Thus, the effectiveness of stem-cell-mediated muscle regeneration is determined by both extrinsic environmental influences and diversity in intrinsic potential of the stem cells themselves.

Aging↗

PubMed2006

Pax7 and myogenic progression in skeletal muscle satellite cells.

Skeletal muscle growth and regeneration are attributed to satellite cells - muscle stem cells resident beneath the basal lamina that surrounds each myofibre. Quiescent satellite cells express the transcription factor Pax7 and when activated, coexpress Pax7 with MyoD. Most then proliferate, downregulate Pax7 and differentiate. By contrast, others maintain Pax7 but lose MyoD and return to a state resembling quiescence. Here we show that Pax7 is able to drive transcription in quiescent and activated satellite cells, and continues to do so in those cells that subsequently cease proliferation and withdraw from immediate differentiation. We found that constitutive expression of Pax7 in satellite-cell-derived myoblasts did not affect MyoD expression or proliferation. Although maintained expression of Pax7 delayed the onset of myogenin expression it did not prevent, and was compatible with, myogenic differentiation. Constitutive Pax7 expression in a Pax7-null C2C12 subclone increased the proportion of cells expressing MyoD, showing that Pax7 can act genetically upstream of MyoD. However these Pax7-null cells were unable to differentiate into normal myotubes in the presence of Pax7. Therefore Pax7 may be involved in maintaining proliferation and preventing precocious differentiation, but does not promote quiescence.

Animals↗

PubMed2006

Satellite cell self-renewal.

Regeneration of adult skeletal muscle involves the activation, proliferation and differentiation of satellite cells - quiescent tissue-specific stem cells occupying a specialised niche beneath the basal laminae of myofibres. Recent studies show that transplanted satellite cells both generate new muscle and undergo self-renewal. Data from cell culture experiments suggest that self-renewal occurs through the return to quiescence of cycling progeny. Several molecules have been implicated in the regulation of satellite cell quiescence, activation and renewal, including the transcription factors Pax7, MyoD and Myf5, the cell-surface glycoprotein CD34, and the membrane lipid sphingomyelin. Evidence suggests that non-satellite cell types from muscle interstitium and bone marrow also give rise to myonuclei, although their contributions relative to the satellite cell remain to be established.

Animals↗

PubMed2005

Self-renewal of the adult skeletal muscle satellite cell.

The concept of the stem cell has evolved in dynamic systems such as those involved in embryonic development and, in the adult, in tissues such as blood and skin which are continuously renewed. It has proved difficult to establish whether stem cell mechanisms underlie the maintenance of the more stable tissues that form the majority of the adult body. We have investigated skeletal muscle, a low-turnover and largely postmitotic tissue which nevertheless maintains a remarkable capacity to regenerate itself following injury. The contractile units of muscle are myofibers, elongated syncytial cells each containing many hundreds of postmitotic myonuclei. Satellite cells are resident beneath the basal lamina of myofibers and function as myogenic precursors during muscle regeneration. We have recently demonstrated that as few as seven Pax7(+) satellite cells associated with one myofiber can regenerate a hundred or more new myofibers containing thousands of myonuclei. Satellite cells also undergo self-renewal, giving them the ability to participate in multiple rounds of injury-induced regeneration. The satellite cell may thus serve as a prototype for stem cell function in stable adult tissues: a tissue-specific progenitor which is normally quiescent but which has self-renewal properties similar to those of better known stem cells.

Animals↗

PubMed2005

Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche.

Satellite cells are situated beneath the basal lamina that surrounds each myofiber and function as myogenic precursors for muscle growth and repair. The source of satellite cell renewal is controversial and has been suggested to be a separate circulating or interstitial stem cell population. Here, we transplant single intact myofibers into radiation-ablated muscles and demonstrate that satellite cells are self-sufficient as a source of regeneration. As few as seven satellite cells associated with one transplanted myofiber can generate over 100 new myofibers containing thousands of myonuclei. Moreover, the transplanted satellite cells vigorously self-renew, expanding in number and repopulating the host muscle with new satellite cells. Following experimental injury, these cells proliferate extensively and regenerate large compact clusters of myofibers. Thus, within a normally stable tissue, the satellite cell exhibits archetypal stem cell properties and is competent to form the basal origin of adult muscle regeneration.

Animals↗

PubMed2002

Randomized, controlled trial of written emotional expression and benefit finding in breast cancer patients.

PURPOSE: Expressing emotions and finding benefits regarding stressful experiences have been associated in correlational research with positive adjustment. A randomized trial was performed to compare effects of experimentally induced written emotional disclosure and benefit finding with a control condition on physical and psychological adjustment to breast cancer and to test whether outcomes varied as a function of participants' cancer-related avoidance. PATIENTS AND METHODS: Early-stage breast cancer patients completing medical treatment were assigned randomly to write over four sessions about (1) their deepest thoughts and feelings regarding breast cancer (EMO group; n = 21), (2) positive thoughts and feelings regarding their experience with breast cancer (POS group; n = 21), or (3) facts of their breast cancer experience (CTL group; n = 18). Psychological (eg, distress) and physical (perceived somatic symptoms and medical appointments for cancer-related morbidities) outcomes were assessed at 1- and 3-month follow-ups. RESULTS: A significant condition x cancer-related avoidance interaction emerged on psychological outcomes; EMO writing was relatively effective for women low in avoidance, and induced POS writing was more useful for women high in avoidance. Significant effects of experimental condition emerged on self-reported somatic symptoms (P =.0183) and medical appointments for cancer-related morbidities (P =.0069). Compared with CTL participants at 3 months, the EMO group reported significantly decreased physical symptoms, and EMO and POS participants had significantly fewer medical appointments for cancer-related morbidities. CONCLUSION: Experimentally induced emotional expression and benefit finding regarding early-stage breast cancer reduced medical visits for cancer-related morbidities. Effects on psychological outcomes varied as a function of cancer-related avoidance.

Adaptation, Psychological↗