Reya Tannishtha
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Recent Prog Horm Res. 2003;58:283-95. doi: 10.1210/rp.58.1.283.
Every day, billions of new blood cells are produced in the body, each one derived from a hematopoietic stem cell (HSC). Because most mature blood stem cells have a limited life span, the ability of HSCs to perpetuate themselves through self-renewal and generate new blood cells for the lifetime of an organism is critical to sustaining life. A key problem in hematopoietic stem cell biology is how HSC self-renewal is regulated. Recent evidence suggests that signaling pathways classically involved in embryonic development--such as the Wnt signaling pathway--play an important role in regulating stem cell self-renewal. The Wnt signaling pathway has been shown to regulate stem cell fate choice in a variety of organs, including the skin, the nervous system, and the hematopoietic system. In the hematopoietic system, stimulation of hematopoietic progenitors and stem cells with soluble Wnt proteins or downstream activators of the Wnt signaling pathway leads to their expansion. Future studies focusing on the mechanism of action of the Wnt signaling pathway and its interaction with other pathways are needed to gain further insight into the regulation of stem cell self-renewal, not only in the hematopoietic system but also in a variety of other tissues.
人体每天会产生数十亿个新的血细胞,每个血细胞都源自造血干细胞(HSC)。由于大多数成熟的血液干细胞寿命有限,造血干细胞通过自我更新维持自身并在生物体的整个生命周期内生成新血细胞的能力对于维持生命至关重要。造血干细胞生物学中的一个关键问题是造血干细胞的自我更新如何受到调控。最近的证据表明,经典的参与胚胎发育的信号通路——如Wnt信号通路——在调节干细胞自我更新中发挥着重要作用。Wnt信号通路已被证明可调节包括皮肤、神经系统和造血系统在内的多种器官中的干细胞命运选择。在造血系统中,用可溶性Wnt蛋白或Wnt信号通路的下游激活剂刺激造血祖细胞和干细胞会导致它们的扩增。未来需要聚焦于Wnt信号通路作用机制及其与其他通路相互作用的研究,以便不仅在造血系统,而且在多种其他组织中更深入地了解干细胞自我更新的调控。