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理解谱系追踪实验中的分裂与合并现象。

Making sense of fragmentation and merging in lineage tracing experiments.

作者信息

Dang Yiteng, Rulands Steffen

机构信息

Max-Planck-Institute for the Physics of Complex Systems, Dresden, Germany.

Center for Systems Biology Dresden, Dresden, Germany.

出版信息

Front Cell Dev Biol. 2022 Dec 14;10:1054476. doi: 10.3389/fcell.2022.1054476. eCollection 2022.

DOI:10.3389/fcell.2022.1054476
PMID:36589749
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9794873/
Abstract

Lineage tracing experiments give dynamic information on the functional behaviour of dividing cells. These experiments therefore have become an important tool for studying stem and progenitor cell fate behavior . When cell proliferation is high or the frequency of induced clones cannot be precisely controlled, the merging and fragmentation of clones renders the retrospective interpretation of clonal fate data highly ambiguous, potentially leading to unguarded interpretations about lineage relationships and fate behaviour. Here, we discuss and generalize statistical strategies to detect, resolve and make use of clonal fragmentation and merging. We first explain how to detect the rates of clonal fragmentation and merging using simple statistical estimates. We then discuss ways to restore the clonal provenance of labelled cells algorithmically and statistically and elaborate on how the process of clonal fragmentation can indirectly inform about cell fate. We generalize and extend results from the context of their original publication.

摘要

谱系追踪实验提供了关于分裂细胞功能行为的动态信息。因此,这些实验已成为研究干细胞和祖细胞命运行为的重要工具。当细胞增殖率高或诱导克隆的频率无法精确控制时,克隆的合并和碎片化使得对克隆命运数据的回顾性解释极具歧义性,可能导致对谱系关系和命运行为的无根据解释。在这里,我们讨论并归纳了检测、解决和利用克隆碎片化与合并的统计策略。我们首先解释如何使用简单的统计估计来检测克隆碎片化和合并的速率。然后,我们讨论通过算法和统计方法恢复标记细胞克隆来源的方法,并详细阐述克隆碎片化过程如何间接反映细胞命运。我们对其原始发表背景下的结果进行了归纳和扩展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f060/9794873/813aa236b005/fcell-10-1054476-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f060/9794873/8d81426f1de2/fcell-10-1054476-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f060/9794873/630cae3cc414/fcell-10-1054476-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f060/9794873/813aa236b005/fcell-10-1054476-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f060/9794873/8d81426f1de2/fcell-10-1054476-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f060/9794873/630cae3cc414/fcell-10-1054476-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f060/9794873/813aa236b005/fcell-10-1054476-g003.jpg

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2
Longitudinal dynamics of clonal hematopoiesis identifies gene-specific fitness effects.克隆性造血的纵向动力学确定了基因特异性的适应性影响。
Nat Med. 2022 Jul;28(7):1439-1446. doi: 10.1038/s41591-022-01883-3. Epub 2022 Jul 4.
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Nature. 2021 Aug;596(7871):211-220. doi: 10.1038/s41586-021-03634-9. Epub 2021 Aug 11.
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Universal principles of lineage architecture and stem cell identity in renewing tissues.在更新组织中谱系架构和干细胞特性的普遍原则。
Development. 2021 Jun 1;148(11). doi: 10.1242/dev.194399. Epub 2021 Jun 8.
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Tracing oncogene-driven remodelling of the intestinal stem cell niche.追踪癌基因驱动的肠道干细胞龛重塑。
Nature. 2021 Jun;594(7863):442-447. doi: 10.1038/s41586-021-03605-0. Epub 2021 Jun 2.
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Stem cell lineage survival as a noisy competition for niche access.干细胞谱系的存活是对小生境准入的一种嘈杂竞争。
Proc Natl Acad Sci U S A. 2020 Jul 21;117(29):16969-16975. doi: 10.1073/pnas.1921205117. Epub 2020 Jul 1.
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Coupled differentiation and division of embryonic stem cells inferred from clonal snapshots.从克隆快照推断胚胎干细胞的偶联分化和分裂。
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