Nature：小环境改变造成造血干细胞功能丧失（附原文）

细胞海洋

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间接证据表明，在衰老过程中造血干细胞和前体细胞功能衰退受来自微环境或干细胞小环境的信号的影响，但一直没有支持这一假设的实验证据。现在，用小鼠所做的一项研究证实，干细胞支撑环境中的细胞所发生的与年龄相关的变化的确能够引起造血干细胞丧失功能。; R7 Q0 u* c1 g" C& l1 Q# [

; Z& l1 c+ E0 H+ T4 _6 ?1 h小环境细胞跟年龄相关的缺陷，是通过暴露于一个年轻的循环系统、或通过对保守型长寿调控因子的中和来系统性地调控和逆转的，该保守型长寿调控因子即骨髓微环境中的“胰岛素样生长因子-1”（IGF-1）。所以，衰老动物血液中的相关因子是通过局部小环境细胞来诱导干细胞与年龄相关的破坏的。这表明，以循环环境为目标来维持小环境细胞和干细胞的功能，也许可以延长老化血液系统的年轻功能+ D9 m" ]1 J+ e+ U* \1 L" n
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原文地址： http://www.stemcell8.cn/thread-17262-1-1.html

细胞海洋

原始出处：
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Nature 463, 495-500 (28 January 2010) | doi:10.1038/nature087496 V9 n9 u  L; c# P9 b1 j5 V5 B0 |

) M2 z+ {+ u- y, K5 ?Systemic signals regulate ageing and rejuvenation of blood stem cell niches
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Shane R. Mayack1, Jennifer L. Shadrach1, Francis S. Kim1 & Amy J. Wagers1
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) P/ i6 p! Y" m' M$ L6 ]. n1 Department of Stem Cell and Regenerative Biology, Harvard University, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02115, USA
6 W0 _. X9 V5 x3 S6 ~. w2 Correspondence to: Amy J. Wagers1 Correspondence and requests for materials should be addressed to A.J.W.0 d/ w! I' S( P

( k0 h  C) X5 k$ e* W$ _Ageing in multicellular organisms typically involves a progressive decline in cell replacement and repair processes, resulting in several physiological deficiencies, including inefficient muscle repair, reduced bone mass, and dysregulation of blood formation (haematopoiesis). Although defects in tissue-resident stem cells clearly contribute to these phenotypes, it is unclear to what extent they reflect stem cell intrinsic alterations or age-related changes in the stem cell supportive microenvironment, or niche. Here, using complementary in vivo and in vitro heterochronic models, we show that age-associated changes in stem cell supportive niche cells deregulate normal haematopoiesis by causing haematopoietic stem cell dysfunction. Furthermore, we find that age-dependent defects in niche cells are systemically regulated and can be reversed by exposure to a young circulation or by neutralization of the conserved longevity regulator, insulin-like growth factor-1, in the marrow microenvironment. Together, these results show a new and critical role for local and systemic factors in signalling age-related haematopoietic decline, and highlight a new model in which blood-borne factors in aged animals act through local niche cells to induce age-dependent disruption of stem cell function

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有没有pdf与大家分享啊？期待中