Postnatal development of the M-band in rat cardiac myofibrils.

Anversa, Piero; Olivetti, G; Bracchi, P.G.; Loud, Alden V.

doi:10.1161/01.res.48.4.561

Cited by 35 publications

(16 citation statements)

References 32 publications

(29 reference statements)

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“…At prenatal stages of differentiation, the myofibrils of most of the mammalian ventricular myocytes, including rats and mice, are devoid of M-lines (for discussion see Rumyantsev 1976Rumyantsev , 1977Rumyantsev , 1991. Similar data were reported by Anversa et al (1981) who found that in rat cardiac muscle, the formation of M-lines occurred during the postnatal period when the myofibrillar contractile apparatus was already very well developed. The results of immunolabeling experiments confirmed the data of electron microscopy.…”

Section: Discussionsupporting

confidence: 89%

Early incorporation of obscurin into nascent sarcomeres: implication for myofibril assembly during cardiac myogenesis

Borisov

Martynova

Russell

2008

Histochem Cell Biol

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Obscurin is a recently identified giant multidomain muscle protein whose functions remain poorly understood. The goal of this study was to investigate the process of assembly of obscurin into nascent sarcomeres during the transition from non-striated myofibril precursors to striated structure of differentiating myofibrils in cell cultures of neonatal rat cardiac myocytes. Double immunofluorescent labeling and high resolution confocal microscopy demonstrated intense incorporation of obscurin in the areas of transition from non-striated to striated regions on the tips of developing myofibrils and at the sites of lateral fusion of nascent sarcomere bundles. We found that obscurin rapidly and precisely accumulated in the middle of the A-band regions of the terminal newly assembled half-sarcomeres in the zones of transition from the continuous, non-striated pattern of sarcomeric α-actinin distribution to cross-striated structure of laterally expanding nascent Z-discs. The striated pattern of obscurin typically ended at these points. This occurred before the assembly of morphologically differentiated terminal Z-discs of the assembling sarcomeres on the tips of growing myofibrils. The presence of obscurin in the areas of the terminal Z-discs of each new sarcomere was detected at the same time or shortly after complete assembly of sarcomeric structure. Many non-striated fibers with very low concentration of obscurin were already immunopositive for sarcomeric actin and myosin. This suggests that obscurin may serve for organization and alignment of myofilaments into the striated pattern. The comparison of obscurin and titin localization in these areas showed that obscurin assembly into the A-bands occurred soon after or concomitantly with incorporation of titin. Electron microscopy of growing myofibrils demonstrated intense formation and integration of myosin filaments into the "open" half-assembled sarcomeres in the areas of the terminal Z-I structures and at the lateral surfaces of newly formed, terminally located nascent sarcomeres. This process progressed before the assembly of the second-formed, terminal Z-discs of new sarcomeres and before the development of ultrastructurally detectable mature M-lines that define the completion of myofibril assembly, which supports the data of immunocytochemical study. Abundant non-aligned sarcomeres in immature myofibrils located on the growing tips were spatially separated and underwent the transition to the registered, aligned pattern. The sarcoplasmic reticulum, © Springer-Verlag 2008 aborisov@umich.edu. This paper is dedicated to the memory of Professor Pavel P. Rumyantsev (1927Rumyantsev ( -1988, a pioneer in studies of cardiac muscle differentiation, who is a lasting inspiration to all who worked with him. the organelle known to interact with obscurin, assembled around each new sarcomere. These results suggest that obscurin is directly involved in the proper positioning and alignment of myofilaments within nascent sarcomeres and in the establishment of the registered ...

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Section: Discussionsupporting

confidence: 89%

Early incorporation of obscurin into nascent sarcomeres: implication for myofibril assembly during cardiac myogenesis

Borisov

Martynova

Russell

2008

Histochem Cell Biol

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“…Myocytes essentially identical to those commonly involved in the prenatal and early postnatal development of the myocardium (89,90) reappear in the diseased human heart, and this process may be mediated by the release from macrophages of a member of the IL-6 inflammatory cytokines, oncostatin M (35). Surprisingly, divid- ing myocytes repeatedly observed in IDC and acute and chronic MI in humans (6,7,10) have not been detected (35).…”

Section: Myocyte Dedifferentiationmentioning

confidence: 99%

Regenerating new heart with stem cells

Anversa

Kajstura²,

Rota³

et al. 2013

J. Clin. Invest.

144

126

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This article discusses current understanding of myocardial biology, emphasizing the regeneration potential of the adult human heart and the mechanisms involved. In the last decade, a novel conceptual view has emerged. The heart is no longer considered a postmitotic organ, but is viewed as a self-renewing organ characterized by a resident stem cell compartment responsible for tissue homeostasis and cardiac repair following injury. Additionally, HSCs possess the ability to transdifferentiate and acquire the cardiomyocyte, vascular endothelial, and smooth muscle cell lineages. Both cardiac and hematopoietic stem cells may be used therapeutically in an attempt to reverse the devastating consequences of chronic heart failure of ischemic and nonischemic origin. IntroductionOur understanding of the process of myocardial regeneration is currently under debate. Although the adult human heart is no longer considered a static organ unable to replace its parenchymal cells during the course of life, the rate of myocyte regeneration reported thus far varies dramatically. Minimal levels of myocyte turnover, which decrease with age, have been claimed (1-5), but results have also been obtained supporting continuous myocyte renewal at a remarkable degree (6-12). Independent from the extent of the process, the debate is further intensified by contrasting views regarding the origin of newly formed cardiomyocytes (13,14). These issues have important implications because knowledge of the magnitude of cell regeneration and the mechanisms involved may offer a novel dynamic perspective of cardiac homeostasis and myocardial biology. This information is critical for the identification of strategies aiming at the restoration of the functional and structural integrity of the failing human heart.The recognition that the adult heart harbors a compartment of multipotent c-kit-positive cardiac stem cells (CSCs) (15-23) and other progenitor cell classes (24-29) capable of differentiating into cardiomyocytes and coronary vessels has raised the challenging question concerning their embryologic origin and role in cardiac cell turnover and regeneration. CSCs are stored in interstitial structures with the characteristics of stem cell niches and can divide symmetrically and asymmetrically, with the ability to self-renew and form a committed progeny (17,21,30). But whether this stem cell pool is actually self-autonomous and fully distinct from HSCs in the bone marrow remains to be determined. c-kit-positive HSCs transdifferentiate and acquire the myocyte, endothelial cell, and smooth muscle cell lineage (31), suggesting that the bone marrow participates in the homeostatic control of the myocardium and the restoration of myocytes and coronary vessels following injury. Additionally, the possibility has been advanced that postmitotic myocytes dedifferentiate, acquire an immature cell phenotype, and then reenter the cell cycle and divide (32-35), representing an alternative or complementary modality of myocyte formation. In this Review, we discuss CSCs, HS...

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“…27 M-band formation was confirmed in the latest stage and has been considered the endpoint of myofibrillar maturation. 18, 21 The lower expression levels of the M-band-specific proteins in the hiPSC-CMs compared with the adult heart might be associated with the delayed appearance of M-bands. Maturation of iPSC-CMs is critical for their application in regenerative medicine, as well as for investigating the mechanisms underlying inherited cardiac diseases.…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural Maturation of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes in a Long-Term Culture

Kamakura

Makiyama

Sasaki

et al. 2013

Circ J

258

224

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Background:In the short-to mid-term, cardiomyocytes generated from human-induced pluripotent stem cells (hiPSC-CMs) have been reported to be less mature than those of adult hearts. However, the maturation process in a long-term culture remains unknown. Methods and Results:A hiPSC clone generated from a healthy control was differentiated into CMs through embryoid body (EB) formation. The ultrastructural characteristics and gene expressions of spontaneously contracting EBs were analyzed through 1-year of culture after cardiac differentiation was initiated. The 14-day-old EBs contained a low number of myofibrils, which lacked alignment, and immature high-density Z-bands lacking A-, H-, I-, and Mbands. Through the long-term culture up to 180 days, the myofibrils became more tightly packed and formed parallel arrays accompanied by the appearance of mature Z-, A-, H-, and I-bands, but not M-bands. Notably, M-bands were finally detected in 360-day-old EBs. The expression levels of the M-band-specific genes in hiPSC-CMs remained lower in comparison with those in the adult heart. Immunocytochemistry indicated increasing number of MLC2v-positive/MLC2a-negative cells with decreasing number of MLC2v/MLC2a double-positive cells, indicating maturing of ventricular-type CMs. Conclusions:The structural maturation process of hiPSC-CMs through 1-year of culture revealed ultrastructural sarcomeric changes accompanied by delayed formation of M-bands. Our study provides new insight into the maturation process of hiPSC-CMs. (Circ J 2013; 77: 1307 -1314

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Postnatal development of the M-band in rat cardiac myofibrils.

Cited by 35 publications

References 32 publications

Early incorporation of obscurin into nascent sarcomeres: implication for myofibril assembly during cardiac myogenesis

Early incorporation of obscurin into nascent sarcomeres: implication for myofibril assembly during cardiac myogenesis

Regenerating new heart with stem cells

Ultrastructural Maturation of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes in a Long-Term Culture

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