Adult satellite cells and embryonic muscle progenitors have distinct genetic requirements.
Adult satellite cells and embryonic muscle progenitors have distinct genetic requirements.
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DOI：
10.1038/nature08209
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发表时间：
2009-07-30
期刊：
影响因子：
64.8
通讯作者：
Fan CM
中科院分区：
文献类型：
--
作者：
Lepper C;Conway SJ;Fan CM
哺乳动物肌肉祖细胞的成肌潜能、存活和扩增在胚胎期依赖于成肌决定因子Pax 3和Pax 7，而在围产期仅依赖于Pax 7。一些体外研究支持Pax 7在成体肌肉干细胞（即卫星细胞）的这些功能中的关键作用，但缺乏体内的正式证明。应用诱导型Cre/loxP谱系追踪和条件基因失活的胫骨前肌再生范例，我们出乎意料地表明，当Pax 7在成年小鼠中失活时，突变卫星细胞在肌肉再生中不受影响，可以增殖和重新占据板层下卫星龛，并支持进一步的再生过程。令人惊讶的是，Pax 3和Pax 7的双重成人失活也导致正常的肌肉再生。多个时间点的基因失活揭示Pax 7仅在祖细胞过渡到静止期的幼年期才需要。我们进一步证明了新生儿祖细胞和成人卫星细胞在Pax 7依赖性方面的细胞内在差异。我们发现肌肉干细胞的遗传需求存在年龄依赖性变化，这一发现提醒我们不要从胚胎研究中推断成体干细胞生物学，并对在基于移植的治疗中使用来自不同年龄宿主的干细胞具有直接影响。
Myogenic potential, survival and expansion of mammalian muscle progenitors depend on the myogenic determinants Pax3 and Pax7 embryonically, and Pax7 alone perinatally. Several in vitro studies support Pax7's critical role in these functions of adult muscle stem cells, i.e. satellite cells, but a formal demonstration has been lacking in vivo. Applying inducible Cre/loxP lineage tracing and conditional gene inactivation to the tibialis anterior muscle regeneration paradigm, we show unexpectedly that when Pax7 is inactivated in adult mice, mutant satellite cells are not compromised in muscle regeneration, can proliferate and reoccupy the sublaminal satellite niche, and support further regenerative processes. Surprisingly, dual adult inactivation of Pax3 and Pax7 also results in normal muscle regeneration. Multiple time points of gene inactivation reveal Pax7 is only required up to the juvenile period when progenitor cells transition into quiescence. We further demonstrate a cell intrinsic difference between neonatal progenitor and adult satellite cells in their Pax7-dependency. Our finding of an age-dependent change in the genetic requirement for muscle stem cells cautions against inferring adult stem cell biology from embryonic studies, and has direct implications for the use of stem cells from hosts of different ages in transplantation-based therapy.
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DOI：
10.1083/jcb.200508001
发表时间：
2006-01-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kuang S;Chargé SB;Seale P;Huh M;Rudnicki MA
通讯作者：
Rudnicki MA
影响因子：
64.8
作者：
Sacco, Alessandra;Doyonnas, Regis;Kraft, Peggy;Vitorovic, Stefan;Blau, Helen M.
通讯作者：
Blau, Helen M.
影响因子：
3.4
作者：
PASTORET, C;SEBILLE, A
通讯作者：
SEBILLE, A
DOI：
10.1006/bbrc.1997.7124
发表时间：
1997-08-28
影响因子：
3.1
作者：
Feil, R;Wagner, J;Chambon, P
通讯作者：
Chambon, P
影响因子：
3.5
作者：
Melcon, G;Kozlov, S;Stewart, CL
通讯作者：
Stewart, CL