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此期Nature上几篇与干细胞相关的有趣研究
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9种不同细胞（包括干细胞）组蛋白动态状态的mapping and analysis。是否以后的干细胞及其分化靶细胞会常规地与成体细胞系统比较鉴定表观遗传。) U+ l0 Z2 z/ k i
$ v# q: C4 J# |4 LMapping and analysis of chromatin state dynamics in nine human cell types
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Z4 G; v1 K8 d1 M: @: C+ ]! GChromatin profiling has emerged as a powerful means of genome annotation and detection of regulatory activity. The approach is especially well suited to the characterization of non-coding portions of the genome, which critically contribute to cellular phenotypes yet remain largely uncharted. Here we map nine chromatin marks across nine cell types to systematically characterize regulatory elements, their cell-type specificities and their functional interactions. Focusing on cell-type-specific patterns of promoters and enhancers, we define multicell activity profiles for chromatin state, gene expression, regulatory motif enrichment and regulator expression. We use correlations between these profiles to link enhancers to putative target genes, and predict the cell-type-specific activators and repressors that modulate them. The resulting annotations and regulatory predictions have implications for the interpretation of genome-wide association studies. Top-scoring disease single nucleotide polymorphisms are frequently positioned within enhancer elements specifically active in relevant cell types, and in some cases affect a motif instance for a predicted regulator, thus suggesting a mechanism for the association. Our study presents a general framework for deciphering cis-regulatory connections and their roles in disease.
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6 w+ C1 {6 Q2 @+ {. q- q& h脂肪细胞激活沉默神经成纤维细胞。营养代谢状况可以调节体内细胞分化和再生？& Y+ d# Z3 {6 C: D' g; |
7 o% ?( R9 C. \0 eFat cells reactivate quiescent neuroblasts via TOR and glial insulin relays in Drosophila* S( L* y8 Q* K1 r2 i( X
1 C. N; R" N' A; RMany stem, progenitor and cancer cells undergo periods of mitotic quiescence from which they can be reactivated1–5. The signals triggering entry into and exit fromthis reversible dormant state are not well understood. In the developing Drosophila central nervous system,multipotent self-renewing progenitors called neuroblasts6–9 undergo quiescence in a stereotypical spatiotemporal pattern10. Entry into quiescence is regulated by Hox proteins and an internal neuroblast timer11–13. Exit from quiescence (reactivation) is subject to a nutritional checkpoint requiring dietary amino acids14. Organ co-cultures also implicate an unidentified signal from an adipose/hepatic-like tissue called the fat body14. Here we provide in vivo evidence that Slimfast amino-acid sensing and Target of rapamycin (TOR) signalling15 activate a fat-body-derived signal (FDS) required for neuroblast reactivation. Downstream of this signal, Insulin-like receptor signalling and the Phosphatidylinositol 3-kinase (PI3K)/TOR network are required in neuroblasts for exit from quiescence. We demonstrate that nutritionally regulated glial cells provide the source of Insulin-like peptides (ILPs) relevant for timely neuroblast reactivation but not for overall larval growth. Conversely, ILPs secreted into the haemolymph by median neurosecretory cells systemically control organismal size16–18 but do not reactivate neuroblasts. Drosophila thus contains two segregated ILP pools, one regulating proliferation within the central nervous system and the other controlling tissue growth systemically. Our findings support a model in which amino acids trigger the cell cycle re-entry of neural progenitors via a fat-body–glia–neuroblasts relay. This mechanism indicates that dietary nutrients and remote organs, as well as local niches, are key regulators of transitions in stem-cell behaviour.
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体外诱导精子。这个新闻已经很著名了，问题是体外制造的精子用于临床的话，会不会带来很多问题。" K, T7 e5 ^2 T% r. Y0 [- b. v
8 R# }* F/ S1 O, H* I4 y! V% lIn vitro production of functional sperm in cultured neonatal mouse testes
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8 @/ @7 f7 B" u& L6 QSpermatogenesis is one of the most complex and longest processes of sequential cell proliferation and differentiation in the body, taking more than a month fromspermatogonial stemcells, through meiosis, to sperm formation1,2. The whole process, therefore, has never been reproduced in vitro in mammals3–5, nor in any other species with a very few exceptions in some particular types of fish6,7. Here we show that neonatal mouse testes which contain only gonocytes or primitive spermatogonia as germ cells can produce spermatids and sperm in vitro with serum-free culture media.7 \9 C2 x) u) y) K
Spermatogenesis wasmaintained over 2months in tissue fragments positioned at the gas–liquid interphase. The obtained spermatids and sperm resulted in healthy and reproductively competent offspring through microinsemination. In addition, neonatal testis tissues were cryopreserved and, after thawing, showed complete spermatogenesis in vitro. Our organ culture method could be applicable through further refinements to a variety of mammalian species, which will serve as a platformfor future clinical application as well as mechanistic understanding of spermatogenesis." p- `+ ~9 w* g9 [/ O3 w
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小鼠不是牛（Developmental Cell上的文章）。如果发育过程中核心多潜能调控机制在哺乳动物中有广泛差异，这个影响还是很大的。
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7 z u3 `% K& ]* |: f0 O, LThe trophectoderm (TE) and inner cell mass (ICM) are committed and marked by reciprocal expression of Cdx2 and Oct4 in mouse late blastocysts. We find that the TE is not committed at equivalent stages in cattle, and that bovine Cdx2 is required later, for TE maintenance, but does not repress Oct4 expression. A mouse Oct4 (mOct4) reporter, repressed in mouse TE, remained active in the cattle TE; bovine Oct4 constructs were not repressed in the mouse TE. mOct4 has acquired Tcfap2 binding sites mediating Cdx2-independent repressioncattle, humans, and rabbits do not contain these sites and maintain high Oct4 levels in the TE. Our data suggest that the regulatory circuitry determining ICM/TE identity has been rewired in mice, to allow rapid TE differentiation and early blastocyst implantation. These findings thus emphasize ways in which mice may not be representative of the earliest stages of mammalian development and stem cell biology. |
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发表于 2011-3-26 23:08
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