Division of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University Hospital, Lund, Sweden.
Blood. 2015 Jun 4;125(23):3542-50. doi: 10.1182/blood-2014-12-618090. Epub 2015 Apr 1.
Blood is a tissue with high cellular turnover, and its production is a tightly orchestrated process that requires constant replenishment. All mature blood cells are generated from hematopoietic stem cells (HSCs), which are the self-renewing units that sustain lifelong hematopoiesis. HSC behavior, such as self-renewal and quiescence, is regulated by a wide array of factors, including external signaling cues present in the bone marrow. The transforming growth factor-β (TGF-β) family of cytokines constitutes a multifunctional signaling circuitry, which regulates pivotal functions related to cell fate and behavior in virtually all tissues of the body. In the hematopoietic system, TGF-β signaling controls a wide spectrum of biological processes, from homeostasis of the immune system to quiescence and self-renewal of HSCs. Here, we review key features and emerging concepts pertaining to TGF-β and downstream signaling pathways in normal HSC biology, featuring aspects of aging, hematologic disease, and how this circuitry may be exploited for clinical purposes in the future.
血液是一种具有高细胞周转率的组织，其生成是一个经过精心协调的过程，需要不断地补充。所有成熟的血细胞都来自造血干细胞（HSCs），HSCs 是维持终生造血的自我更新单位。HSC 的行为，如自我更新和静止，受到多种因素的调节，包括骨髓中存在的外部信号线索。转化生长因子-β（TGF-β）细胞因子家族构成了一个多功能的信号通路，它调节与细胞命运和行为相关的关键功能，几乎涉及身体的所有组织。在造血系统中，TGF-β信号控制着广泛的生物学过程，从免疫系统的稳态到 HSCs 的静止和自我更新。在这里，我们回顾了 TGF-β及其下游信号通路在正常 HSC 生物学中的关键特征和新出现的概念，重点介绍了衰老、血液疾病以及该电路如何在未来为临床目的所利用的方面。
