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新兴的单细胞工具正准备揭示恶性造血干细胞中的功能和分子异质性。

Emerging single-cell tools are primed to reveal functional and molecular heterogeneity in malignant hematopoietic stem cells.

机构信息

Wellcome-MRC Cambridge Stem Cell Institute.

Department of Haematology, University of Cambridge, Cambridge, UK.

出版信息

Curr Opin Hematol. 2019 Jul;26(4):214-221. doi: 10.1097/MOH.0000000000000512.

Abstract

PURPOSE OF REVIEW

The recent emergence of single-cell technologies has permitted unprecedented insight into the molecular drivers of fate choice in blood stem and progenitor cells. This review gives a broad overview of current efforts to understand the molecular regulators of malignant hematopoietic stem cells (HSCs) at the single-cell level.

RECENT FINDINGS

The large-scale adoption of single-cell approaches has allowed extensive description of the transcriptional profiles and functional properties of single HSCs. These techniques are now beginning to be applied to malignant HSCs isolated directly from patients or from mouse models of malignancy. However, these studies have generally struggled to pinpoint the functional regulators of malignant characteristics, since malignant HSCs often differ in more than one property when compared with normal HSCs. Moreover, both normal and malignant populations are complicated by HSC heterogeneity.

SUMMARY

Despite the existence of single-cell gene expression profiling tools, relatively few publications have emerged. Here, we review these studies from recent years with a specific focus on those undertaking single-cell measurements in malignant stem and progenitor cells. We anticipate this to be the tip of the iceberg, expecting the next 2-3 years to produce datasets that will facilitate a much broader understanding of malignant HSCs.

摘要

目的综述

单细胞技术的最新出现使得人们能够以前所未有的方式深入了解血液干/祖细胞中命运选择的分子驱动因素。本综述广泛概述了目前在单细胞水平上理解恶性造血干/祖细胞(HSC)的分子调控因子的努力。

最近的发现

单细胞方法的大规模采用使得对单个 HSC 的转录谱和功能特性进行广泛描述成为可能。这些技术现在开始应用于直接从患者或恶性肿瘤小鼠模型中分离的恶性 HSC。然而,这些研究通常难以确定恶性特征的功能调节剂,因为与正常 HSC 相比,恶性 HSC 在多个属性上往往存在差异。此外,正常和恶性群体都因 HSC 异质性而变得复杂。

总结

尽管存在单细胞基因表达谱分析工具,但发表的相关研究相对较少。在这里,我们重点回顾了近年来的这些研究,特别是那些在恶性干细胞和祖细胞中进行单细胞测量的研究。我们预计这只是冰山一角,期待未来 2-3 年能产生更多数据集,从而更广泛地了解恶性 HSC。

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