Dynamic heterogeneity as a strategy of stem cell self-renewal

Author:

Greulich Philip,Simons Benjamin D.

Abstract

To maintain cycling adult tissue in homeostasis the balance between proliferation and differentiation of stem cells needs to be precisely regulated. To investigate how stem cells achieve perfect self-renewal, emphasis has been placed on models in which stem cells progress sequentially through a one-way proliferative hierarchy. However, investigations of tissue regeneration have revealed a surprising degree of flexibility, with cells normally committed to differentiation able to recover stem cell competence following injury. Here, we investigate whether the reversible transfer of cells between states poised for proliferation or differentiation may provide a viable mechanism for a heterogeneous stem cell population to maintain homeostasis even under normal physiological conditions. By addressing the clonal dynamics, we show that such models of “dynamic heterogeneity” may be equally capable of describing the results of recent lineage tracing assays involving epithelial tissues. Moreover, together with competition for limited niche access, such models may provide a mechanism to render tissue homeostasis robust. In particular, in 2D epithelial layers, we show that the mechanism of dynamic heterogeneity avoids some pathological dependencies that undermine models based on a hierarchical stem/progenitor organization.

Funder

Engineering and Physical Sciences Research Council

Deutsche Forschungsgemeinschaft

Wellcome Trust

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Cited by 54 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3