Although B lymphopoiesis is one of the best-defined paradigms in cell differentiation, our knowledge of the regulatory mechanisms underlying its earliest processes, in which hematopoietic stem cells (HSCs) enter the B lineage, is limited. However, recent methodological advances in sorting progenitor cells and monitoring their epigenetic features have increased our understanding of HSC activities. It is now known that even the highly enriched HSC fraction is heterogeneous in terms of lymphopoietic potential. While surface markers and reporter proteins provide information on the sequential differentiation of B-lineage progenitors, complex interactions between transcription factors have also been shown to play a major role in this process. Epigenetic regulation of histones, nucleosomes, and chromatin appears to play a crucial background role in this elaborate transcription network. In this review, we summarize recent findings on the physiological processes of early B-lineage differentiation, which provides a new paradigm for understanding the harmonious action of genetic and epigenetic mechanisms.

译文

:尽管B淋巴细胞生成是细胞分化中定义最明确的范例之一,但我们对其最早过程(造血干细胞(HSC)进入B谱系)的调控机制的了解有限。但是,最近在分类祖细胞和监测其表观遗传学特征方面的方法学进展增加了我们对HSC活性的了解。现在已知,就淋巴生成潜力而言,即使高度富集的HSC部分也是异质的。尽管表面标志物和报告蛋白提供了有关B系祖细胞顺序分化的信息,但转录因子之间的复杂相互作用在该过程中也发挥了重要作用。组蛋白,核小体和染色质的表观遗传调控似乎在这个复杂的转录网络中起着至关重要的背景作用。在这篇综述中,我们总结了关于早期B谱系分化的生理过程的最新发现,这为理解遗传和表观遗传机制的协调作用提供了新的范例。

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