Transcriptional analysis of histone deacetylase family members reveal similarities between differentiating and aging spermatogonial stem cells.
Transcriptional analysis of histone deacetylase family members reveal similarities between differentiating and aging spermatogonial stem cells.
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DOI：
10.1007/s12015-012-9392-5
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发表时间：
2013-02
影响因子：
4.8
通讯作者：
Payne, Christopher J.
中科院分区：
文献类型：
--
作者：
Kofman, Amber E.;Huszar, Jessica M.;Payne, Christopher J.
成体干细胞的分化涉及广泛的染色质重塑，部分由组蛋白去乙酰化酶（HDAC）家族成员的基因产物介导。虽然HDAC的转录下调在某些情况下可以阻碍干细胞自我更新，但它也可能在其他情况下促进干细胞维持。在自我更新、分化和老化的精原干细胞（SSC）中，HDACs的基因表达动态尚未被表征。为了进一步了解这些研究，我们分析了6个HDAC家族成员的转录谱，这些成员先前被确定为在干细胞分化和衰老过程中在自我更新的SSC中表达最高。在这里，我们发现在分化和老化的SSC中，Sirt4的表达增加，而Hdac2，Hdac6和Sirt1的表达减少。当SSC在体内暴露于延长寿命的药物雷帕霉素时，所得的HDAC基因表达模式与分化和老化的SSC中所见的相反，Hdac2，Hdac6和Sirt1增加，Hdac8，Hdac9和Sirt4减少。我们的研究结果表明，HDAC重要的干细胞的维护和氧化能力下调成人干细胞分化或年龄。这些结果为哺乳动物干细胞分化和衰老的表观遗传调控提供了重要的见解。
The differentiation of adult stem cells involves extensive chromatin remodeling, mediated in part by the gene products of histone deacetylase (HDAC) family members. While the transcriptional downregulation of HDACs can impede stem cell self-renewal in certain contexts, it may also promote stem cell maintenance under other circumstances. In self-renewing, differentiating, and aging spermatogonial stem cells (SSCs), the gene expression dynamics of HDACs have not yet been characterized. To gain further insight with these studies, we analyzed the transcriptional profiles of six HDAC family members, previously identified to be the most highly expressed in self-renewing SSCs, during stem cell differentiation and aging. Here we discovered that in both differentiating and aging SSCs the expression of Sirt4 increases, while the expression of Hdac2, Hdac6, and Sirt1 decreases. When SSCs are exposed to the lifespan-enhancing drug rapamycin in vivo, the resultant HDAC gene expression patterns are opposite of those seen in the differentiating and aging SSCs, with increased Hdac2, Hdac6, and Sirt1 and decreased Hdac8, Hdac9, and Sirt4. Our findings suggest that HDACs important for stem cell maintenance and oxidative capacity are downregulated as adult stem cells differentiate or age. These results provide important insights into the epigenetic regulation of stem cell differentiation and aging in mammals.
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影响因子：
64.5
作者：
Hobbs RM;Seandel M;Falciatori I;Rafii S;Pandolfi PP
通讯作者：
Pandolfi PP
影响因子：
3.6
作者：
Shima, JE;McLean, DJ;Griswold, MD
通讯作者：
Griswold, MD
DOI：
10.1196/annals.1395.039
发表时间：
2007-01-01
期刊：
BIOGERONTOLOGY: MECHANISMS AND INTERVENTIONS
影响因子：
--
作者：
Sekeri-Pataryas, Kalliope E.;Sourlingas, Thomae G.
通讯作者：
Sourlingas, Thomae G.
影响因子：
8.5
作者：
Lee, S.;Park, J-R.;Kang, K-S.
通讯作者：
Kang, K-S.
影响因子：
29
作者：
Bjedov I;Toivonen JM;Kerr F;Slack C;Jacobson J;Foley A;Partridge L
通讯作者：
Partridge L