Analysis of myogenesis by somatic cell hybridization: III. Myogenic competence of hybrids derived from rat L6 myoblasts and mouse primary fibroblasts and myoblasts

Konieczny, Stephen F.; Coleman, John R.

doi:10.1007/bf01544046

Cited by 4 publications

(1 citation statement)

References 25 publications

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“…Our results differ from two recent reports involving myogenic cell hybrids (33,34). Lawrence and Coleman found that hybrids between competent and differentiation-defective L6 myoblasts exhibited high rather than intermediate levels ofdifferentiation (33).…”

Section: Discussioncontrasting

confidence: 99%

Control of differentiation in heterokaryons and hybrids involving differentiation-defective myoblast variants.

Wright¹

1984

The Journal of Cell Biology

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Clones of differentiation-defective myoblasts were isolated by selecting clones of L6 rat myoblasts that did not form myotubes under differentiation-stimulating conditions. Rat skeletal myosin light chain synthesis was induced in heterokaryons formed by fusing these defective myoblasts to differentiated chick skeletal myocytes. This indicates that the structural gene for this muscle protein was still responsive to chick inducing factors and that the defective myoblasts were not producing large quantities of molecules that dominantly suppressed the expression of differentiated functions . The regulation of the decision to differentiate was then examined in hybrids between differentiation-defective myoblasts and differentiation-competent myoblasts . Staining with antimyosin antibodies showed that the defective myoblasts and homotypic hybrids formed by fusing defective myoblasts to themselves could in fact differentiate, but did so more than a thousand times less frequently than the 64% differentiation achieved by competent L6 myoblasts or homotypic competent x competent L6 hybrids . Heterotypic hybrids between differentiation-defective myoblasts and competent L6 cells exhibited an intermediate behavior of -1% differentiation . A theoretical model for the regulation of the commitment to terminal differentiation is proposed that could explain these results by invoking the need to achieve threshold levels of secondary inducing molecules in response to differentiation-stimulating conditions. This model helps explain many of the stochastic aspects of cell differentiation .During the past twenty years cultured cells have become one ofthe most,important tools for the study ofcell differentiation . Unfortunately, the expression of differentiated functions is frequently unstable under conditions of continuous cell culture (1-7). Although overgrowth ofthe differentiated cell type by "fibroblastoid cells" is often invoked as the cause in primary cultures, there is good evidence in some systems that differentiated diploid cells can "dedifferentiate" and reduce their synthesis of differentiated products (2, 3, 7). This loss of differentiated functions is also observed in cloned established cell lines where, if overgrowth is the cause, it is overgrowth by a dedifferentiated variant arising within the cloned population .The mechanisms by which cells lose the capacity to express differentiated functions and the nature of the differentiated program in nonexpressing variants are important issues for understanding the regulation and maintenance of cell differentiation. In the present study we have approached this problem by examining the regulation of muscle functions in heterokaryons and cell hybrids involving differentiation-defective myoblasts. We have previously shown that rat skeletal myosin light chain synthesis is induced when undifferentiated rat myoblasts are fused with polyethylene glycol to mononucleated differentiated chick skeletal myocytes (8,9). This suggests that differentiated chick myocytes contain factors...

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Section: Discussioncontrasting

confidence: 99%

Control of differentiation in heterokaryons and hybrids involving differentiation-defective myoblast variants.

Wright¹

1984

The Journal of Cell Biology

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Analysis of myogenesis by somatic cell hybridization. II. Retention of myogenic competence and suppression of transformed properties in hybrids between differentiation competent and incompetent rat L6 myoblasts

Lawrence

Coleman

1983

Journal Cellular Physiology

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This study describes the characteristics of hybrids between two closely related rat myoblast lines, which differ both in the ability to express their program of differentiation and in the expression of neoplastic properties. Myogenic, nonneoplastic L6J1-S cells were hybridized with nonmyogenic, neoplastic L6J1-N1 cells. Six hybrid clones were isolated and expanded for analysis of myogenic competence, and four of these clones were also evaluated for parameters of transformation, including tumorigenicity, ability to clone in agar, and surface fibronectin. In addition to our analysis of isolated clones, we also assessed myogenic differentiation in colonies representing 226 early hybrid clones. Results of all these analyses demonstrate that the myogenic phenotype is retained and that the tumorigenic/transformed phenotype is suppressed in the hybrids. Furthermore, our results indicate that when the programs for myogenesis and neoplastic transformation are confronted within a single cell, they are expressed as mutually exclusive alternatives. In contrast to these results on myogenic X nonmyogenic L6 hybrids, it has been reported that isolated clones of A9 X L6 exhibited extinction of myogenic competence and retention of transformed properties. We have evaluated myotube formation in over 300 early hybrid clones between A9 and either diploid or subtetraploid L8 rat myoblasts. Our results demonstrate that all of these hybrid clones exhibit extinction regardless of the ploidy of the myoblast parent, and they further indicate that extinction is not a consequence of chromosome loss. These results support the conclusion that in A9 X L6 hybrids, the nonmyogenic, transformed phenotype is dominant.

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Expression of differentiated functions in heterokaryons between skeletal myocytes, adrenal cells, fibroblasts and glial cells

Wright

1984

Experimental Cell Research

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Analysis of myogenesis by somatic cell hybridization: III. Myogenic competence of hybrids derived from rat L6 myoblasts and mouse primary fibroblasts and myoblasts

Cited by 4 publications

References 25 publications

Control of differentiation in heterokaryons and hybrids involving differentiation-defective myoblast variants.

Control of differentiation in heterokaryons and hybrids involving differentiation-defective myoblast variants.

Analysis of myogenesis by somatic cell hybridization. II. Retention of myogenic competence and suppression of transformed properties in hybrids between differentiation competent and incompetent rat L6 myoblasts

Expression of differentiated functions in heterokaryons between skeletal myocytes, adrenal cells, fibroblasts and glial cells

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