De novo hematopoietic (stem) cell generation - A differentiation or stochastic process?
De novo hematopoietic (stem) cell generation - A differentiation or stochastic process?
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DOI：
10.1016/j.ceb.2023.102255
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发表时间：
2023-10-06
影响因子：
7.5
通讯作者：
Dzierzak，Elaine
中科院分区：
文献类型：
--
作者：
Vink，Chris S.;Popravko，Anna;Dzierzak，Elaine
造血系统是最早发育的组织之一。造血祖细胞和干细胞的去新生是通过(造血)内皮细胞向造血细胞的转分化而发生的，导致主动脉内造血簇(IAHC)细胞的形成。IAHC细胞表型和功能的异质性阻碍了该领域寻找新出现的造血干细胞(HSCs)的转录计划，因为单个IAHC不能同时检测功能和转录组。有几个模型可以解释这种异质性，包括一个新的模型，该模型表明单个新出现的IAHC细胞的转录处于不稳定/亚稳定状态，由于转录脉冲和组合活性，关键的造血转录因子动态表达。问题仍然存在--功能性造血细胞的命运是如何确定的--这个过程是随机的吗？这篇文章涉及到这些重要的问题，这些问题可能与该领域无法在体内进行HSC性相关。
The hematopoietic system is one of the earliest tissues to develop.De novogeneration of hematopoietic progenitor and stem cells occurs through a transdifferentiation of (hemogenic) endothelial cells to hematopoietic identity, resulting in the formation of intra-aortic hematopoietic cluster (IAHC) cells. Heterogeneity of IAHC cell phenotypes and functions has stymied the field in its search for the transcriptional program of emerging hematopoietic stem cells (HSCs), given that an individual IAHC cannot be simultaneously examined for function and transcriptome. Several models could account for this heterogeneity, including a novel model suggesting that the transcriptomes of individual emerging IAHC cells are in an unstable/metastable state, with pivotal hematopoietic transcription factors expressed dynamically due to transcriptional pulsing and combinatorial activities. The question remains — how is functional hematopoietic cell fate established — is the process stochastic? This article touches upon these important issues, which may be relevant to the field's inability to make HSCsex vivo.