Resolving the hematopoietic stem cell state by linking functional and molecular assays.

Resolving the hematopoietic stem cell state by linking functional and molecular assays.
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DOI:
10.1182/blood.2022017864
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发表时间:
2023-08-10
期刊:
影响因子:
20.3
通讯作者:
Kent, David G.
Kent, David G.
中科院分区:
医学1区
文献类型:
--
作者:
Jassinskaja, Maria;Gonka, Monika;Kent, David G.

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干细胞研究最具挑战性的方面之一是依赖追溯分析来确定功能。这对造血干细胞(HSC)研究尤其有问题,因为目前正式确定其HSC身份的功能测试涉及长期的连续移植测试,在知道它实际上是HSC之前,必须在许多个月前破坏初始细胞状态。与同样破坏性的单细胞分子分析的爆炸性相结合,研究人员面临的悖论是,当你无法同时评估其功能和分子特性时,如何确定功能HSC的分子状态。在这篇综述中,我们将对该领域中的功能和分子分析进行历史回顾,确定在HSC群体中结合分子和功能读数的新工具,并设想下一代计算和分子图谱工具,这些工具可能有助于我们更好地将细胞功能与分子状态联系起来。这一综述系列由副主编John Crispino编辑,重点关注造血干细胞(HSC)生物学,超越了小鼠HSC生物学的工作,强调人类HSC的发育和特征。该领域的专家作者涵盖了从个体发育到衰老和白血病转化的各种主题。我们希望这些博学的文章将促进研究,开发新的策略来逆转衰老的影响,防止恶性转化,并提高从多能干细胞体外产生HSCs。
One of the most challenging aspects of stem cell research is the reliance on retrospective assays for ascribing function. This is especially problematic for hematopoietic stem cell (HSC) research in which the current functional assay that formally establishes its HSC identity involves long-term serial transplantation assays that necessitate the destruction of the initial cell state many months before knowing that it was, in fact, an HSC. In combination with the explosion of equally destructive single-cell molecular assays, the paradox facing researchers is how to determine the molecular state of a functional HSC when you cannot concomitantly assess its functional and molecular properties. In this review, we will give a historical overview of the functional and molecular assays in the field, identify new tools that combine molecular and functional readouts in populations of HSCs, and imagine the next generation of computational and molecular profiling tools that may help us better link cell function with molecular state. Edited by Associate Editor John Crispino, this Review Series focuses on hematopoietic stem cell (HSC) biology, going beyond the work in murine HSC biology and emphasizing development and characterization of human HSCs. Expert authors in the field cover topics ranging from ontogeny to aging and leukemia transformation. We hope that these erudite articles will stimulate research that develops novel strategies to reverse the effects of aging, prevent malignant transformation, and enhance in vitro production of HSCs from pluripotent stem cells.
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