Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, Texas, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, USA.
Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, Texas, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Curr Top Dev Biol. 2014;107:39-75. doi: 10.1016/B978-0-12-416022-4.00002-0.
Hematopoietic development and homeostasis are based on hematopoietic stem cells (HSCs), a pool of ancestor cells characterized by the unique combination of self-renewal and multilineage potential. These two opposing forces are finely orchestrated by several regulatory mechanisms, comprising both extrinsic and intrinsic factors. Over the past decades, several studies have contributed to dissect the key role of niche factors, signaling transduction pathways, and transcription factors in HSC development and maintenance. Accumulating evidence, however, suggests that a higher level of intrinsic regulation exists; epigenetic marks, by controlling chromatin accessibility, directly shape HSC developmental cascades, including their emergence during embryonic development, maintenance of self-renewal, lineage commitment, and aging. In addition, aberrant epigenetic marks have been found in several hematological malignancies, consistent with clinical findings that mutations targeting epigenetic regulators promote leukemogenesis. In this review, we will focus on both normal and malignant hematopoiesis, covering recent findings that illuminate the epigenetic life of HSCs.
造血的发生和稳态依赖于造血干细胞（HSCs），其作为一个祖细胞池，以自我更新和多系分化潜能的独特组合为特征。这两种相反的力量由几种调节机制精细地协调，包括外在和内在因素。在过去的几十年中，多项研究有助于解析龛因子、信号转导途径和转录因子在 HSC 发生和维持中的关键作用。然而，越来越多的证据表明存在更高水平的内在调节；通过控制染色质可及性，表观遗传标记直接塑造 HSC 发育级联，包括它们在胚胎发育过程中的出现、自我更新的维持、谱系决定以及衰老。此外，在几种血液恶性肿瘤中发现了异常的表观遗传标记，这与临床发现一致，即针对表观遗传调节剂的突变可促进白血病的发生。在这篇综述中，我们将重点关注正常和恶性造血，涵盖了阐明 HSCs 表观遗传本质的最新发现。
