Self-renewal and expansion of single transplanted muscle stem cells.

Self-renewal and expansion of single transplanted muscle stem cells.
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DOI:
10.1038/nature07384
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发表时间:
2008-11-27
期刊:
影响因子:
64.8
通讯作者:
Blau, Helen M.
Blau, Helen M.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Sacco, Alessandra;Doyonnas, Regis;Kraft, Peggy;Vitorovic, Stefan;Blau, Helen M.

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成体肌肉卫星细胞在出生后骨骼肌的生长和再生中起主要作用。卫星细胞以静止细胞的形式存在于包围着肌肉纤维的基板下,并通过产生瞬时放大细胞(祖细胞)和与肌纤维融合的成肌细胞来对损伤做出反应。最近的实验表明,与培养的成肌细胞相比,新鲜分离的卫星细胞或移植一个完整的肌纤维产生的卫星细胞对肌肉修复有很大的促进作用。然而,由于卫星细胞是已知的异质性,需要克隆分析来证明干细胞的功能。在这里,我们展示了当单个表达荧光素酶的肌肉干细胞被移植到小鼠的肌肉中时,它能够广泛增殖,有助于肌肉纤维,并且Pax7+荧光素酶+单核细胞可以很容易地重新分离,这为肌肉干细胞自我更新提供了证据。此外,我们使用体内生物发光成像显示,肌肉修复过程中肌肉干细胞行为的动态可以以一种传统的回溯性组织学分析不可能跟踪的方式进行跟踪。通过成像荧光素酶活性,实时定量和动力学分析表明,供体来源的肌肉干细胞在注射后迅速增殖和植入,直到达到动态平衡。在损伤时,供体来源的单核细胞会产生大量的细胞增殖浪潮。综上所述,这些结果表明单个表达荧光素酶的肌肉干细胞的后代在小鼠体内移植后既能自我更新又能分化,在克隆水平上为自我更新是单个成年肌肉干细胞的自主属性提供了新的证据。
Adult muscle satellite cells have a principal role in postnatal skeletal muscle growth and regeneration. Satellite cells reside as quiescent cells underneath the basal lamina that surrounds muscle fibres and respond to damage by giving rise to transient amplifying cells (progenitors) and myoblasts that fuse with myofibres. Recent experiments showed that, in contrast to cultured myoblasts, satellite cells freshly isolated or satellite cells derived from the transplantation of one intact myofibre contribute robustly to muscle repair. However, because satellite cells are known to be heterogeneous, clonal analysis is required to demonstrate stem cell function. Here we show that when a single luciferase-expressing muscle stem cell is transplanted into the muscle of mice it is capable of extensive proliferation, contributes to muscle fibres, and Pax7+luciferase+ mononucleated cells can be readily re-isolated, providing evidence of muscle stem cell self-renewal. In addition, we show using in vivo bioluminescence imaging that the dynamics of muscle stem cell behaviour during muscle repair can be followed in a manner not possible using traditional retrospective histological analyses. By imaging luciferase activity, real-time quantitative and kinetic analyses show that donor-derived muscle stem cells proliferate and engraft rapidly after injection until homeostasis is reached. On injury, donor-derived mononucleated cells generate massive waves of cell proliferation. Together, these results show that the progeny of a single luciferase-expressing muscle stem cell can both self-renew and differentiate after transplantation in mice, providing new evidence at the clonal level that self-renewal is an autonomous property of a single adult muscle stem cell.
DOI: 10.1083/jcb.200312007
发表时间: 2004-08-02
期刊: The Journal of cell biology
影响因子: --
作者:
Zammit PS;Golding JP;Nagata Y;Hudon V;Partridge TA;Beauchamp JR
通讯作者: Beauchamp JR
DOI: 10.1016/j.cell.2004.10.021
发表时间: 2004-11-12
期刊: CELL
影响因子: 64.5
作者:
Sherwood, RI;Christensen, JL;Wagers, AJ
通讯作者: Wagers, AJ
DOI: 10.1016/s1534-5807(02)00254-x
发表时间: 2002-09-01
期刊: DEVELOPMENTAL CELL
影响因子: 11.8
作者:
Conboy, IM;Rando, TA
通讯作者: Rando, TA
DOI: 10.1073/pnas.2637010100
发表时间: 2004-01-06
影响因子: 11.1
作者:
Cao, YA;Wagers, AJ;Contag, CH
通讯作者: Contag, CH
DOI: 10.1083/jcb.200506123
发表时间: 2005-11-07
影响因子: 7.8
作者:
Sacco, A;Doyonnas, R;Blau, HM
通讯作者: Blau, HM