《Nature》年轻的“秘诀”在干细胞Niche

　　

生物通报道，哈佛大学医学院干细胞与再生生物学系，哈佛干细胞研究院，Howard Hughes医学研究所，Joslin糖尿病中心的科学家在最新一期的Nature杂志上发表干细胞再生话题的研究进展文章Systemic signals regulate ageing and rejuvenation of blood stem cell niches。

 

老化是所有多细胞生命体无法避免的话题，随着年龄的增大以及细胞自我复制的能力降低，生命体开始出现系列的生理衰退现象，包括，肌肉修复功能丧失，骨髓量减少，造血功能衰退等等。

 

尽管，科学家们一直都知道，衰老变化的根源来自干细胞的变化，但是，究竟干细胞发生怎样的变化才会导致衰老一直是个悬而未决的问题。

 

为此，哈佛大学的科学家们尝试从干细胞微环境（也称为Niche）入手，研究衰老与干细胞微环境的变化之间的关联。干细胞周围的细胞形成像摇篮样的环境保护着干细胞，这一环境被称为niche。niche不仅给干细胞提供养分，同时还指导干细胞的行动，决定干细胞的分化方向。

 

研究小组发现，随着年龄增长而发生的干细胞微环境的变化可通过调整到新的环境（年轻的微环境）而得到改善和逆转，也就是说，可以直接逆转衰老的过程。此外，科学家们还发现除了给干细胞更换新的微环境外，还可以通过一种调节因子“胰岛素样生长因子-1”（IGF-1）来进行改善。

 

这些数据表明，造血功能的丧失与系统化的信号环境的改变有关，科学家们依照这种新的思路可改善因衰老而退化的造血机能，并且更好地研究干细胞的微环境功能。

（生物通 小茜）

 

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生物通推荐原文检索

Nature 463, 495-500 (28 January 2010) | doi:10.1038/nature08749; Received 26 August 2009; Accepted 6 December 2009

Systemic signals regulate ageing and rejuvenation of blood stem cell niches

Shane R. Mayack1, Jennifer L. Shadrach1, Francis S. Kim1 & Amy J. Wagers1

 

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

Correspondence to: Amy J. Wagers1 Correspondence and requests for materials should be addressed to A.J.W. (Email: [e-mail]).

 

 

【Abstract】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.