華盛頓卡耐基研究所胚胎發(fā)育系,約翰霍普金斯大學(xué)生物系,印第安大大學(xué)醫(yī)學(xué)院的研究人員在最新的Nature在線版上發(fā)布干細(xì)胞研究新成果,。
干細(xì)胞分成體干細(xì)胞(Adult Stem Cell)和胚胎干細(xì)胞(Embryonic Stem Cell)兩種,兩者的細(xì)胞特征和分化潛能都具有差異,當(dāng)然,兩種干細(xì)胞在發(fā)育過程中起調(diào)控作用的基因也各不相同,。
本研究主要以哺乳動物的肌細(xì)胞為研究模型,在胚胎發(fā)育前期,,哺乳動物肌細(xì)胞的祖細(xì)胞其生肌潛能,,存活能力,遷移能力等都依賴于Pax3和Pax7,,但是圍產(chǎn)期間,,僅Pax7對祖細(xì)胞的發(fā)育起關(guān)鍵調(diào)控作用。
在目前的研究中,,對Pax7的調(diào)節(jié)功能的研究已經(jīng)受幾個體外實驗數(shù)據(jù)支持,,但是缺乏活體實驗的驗證,。
在本篇研究中,,研究小組以小鼠模型證實了這一觀點。并且證實成體肌肉干細(xì)胞不受Pax3和Pax7的調(diào)控,,當(dāng)研究小組將兩基因失活后,,成年小鼠的肌肉再生不受影響。
這些干細(xì)胞發(fā)育基因調(diào)控差異的發(fā)現(xiàn)有助科學(xué)家更深入了解干細(xì)胞的發(fā)育,,尤其對將來干細(xì)胞臨床移植具有指導(dǎo)性意義,。(生物谷Bioon.com)
生物谷推薦原始出處:
Nature 25 June 2009 | doi:10.1038/nature08209
Adult satellite cells and embryonic muscle progenitors have distinct genetic requirementsnear-final version
Christoph Lepper1,2, Simon J. Conway3 & Chen-Ming Fan1
1 Department of Embryology, Carnegie Institution, 3520 San Martin Drive, Baltimore, Maryland 21218, USA
2 Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA
3 Riley Heart Research Center, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
Myogenic potential, survival and expansion of mammalian muscle progenitors depend on the myogenic determinants Pax3 and Pax7 embryonically1, and Pax7 alone perinatally2, 3, 4, 5. Several in vitro studies support the critical role of Pax7 in these functions of adult muscle stem cells5, 6, 7, 8 (satellite cells), but a formal demonstration has been lacking in vivo. Here we show, through the application of inducible Cre/loxP lineage tracing9 and conditional gene inactivation to the tibialis anterior muscle regeneration paradigm, that, unexpectedly, when Pax7 is inactivated in adult mice, mutant satellite cells are not compromised in muscle regeneration, they can proliferate and reoccupy the sublaminal satellite niche, and they are able to support further regenerative processes. Dual adult inactivation of Pax3 and Pax7 also results in normal muscle regeneration. Multiple time points of gene inactivation reveal that Pax7 is only required up to the juvenile period when progenitor cells make the transition into quiescence. Furthermore, we 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.