Department of Medical Sciences, Section of Experimental Medicine, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
Department of Medical Sciences, Section of Experimental Medicine, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
Int Rev Cell Mol Biol. 2021;362:111-140. doi: 10.1016/bs.ircmb.2021.05.003. Epub 2021 Jun 21.
Hematopoiesis is based on the existence of hematopoietic stem cells (HSC) with the capacity to self-proliferate and self-renew or to differentiate into specialized cells. The hematopoietic niche is the essential microenvironment where stem cells reside and integrate various stimuli to determine their fate. Recent studies have identified niche containing high level of calcium (Ca) suggesting that HSCs are sensitive to Ca. This is a highly versatile and ubiquitous second messenger that regulates a wide variety of cellular functions. Advanced methods for measuring its concentrations, genetic experiments, cell fate tracing data, single-cell imaging, and transcriptomics studies provide information into its specific roles to integrate signaling into an array of mechanisms that determine HSC identity, lineage potential, maintenance, and self-renewal. Accumulating and contrasting evidence, are revealing Ca as a previously unacknowledged feature of HSC, involved in functional maintenance, by regulating multiple actors including transcription and epigenetic factors, Ca-dependent kinases and mitochondrial physiology. Mitochondria are significant participants in HSC functions and their responsiveness to cellular demands is controlled to a significant extent via Ca signals. Recent reports indicate that mitochondrial Ca uptake also controls HSC fate. These observations reveal a physiological feature of hematopoietic stem cells that can be harnessed to improve HSC-related disease. In this review, we discuss the current knowledge Ca in hematopoietic stem cell focusing on its potential involvement in proliferation, self-renewal and maintenance of HSC and discuss future research directions.
造血是基于造血干细胞（HSC）的存在，这些细胞具有自我增殖和自我更新的能力，或者分化为专门的细胞。造血龛是干细胞所在的必要微环境，整合各种刺激因素以确定其命运。最近的研究表明，龛内含有高水平的钙（Ca），提示 HSC 对 Ca 敏感。Ca 是一种高度多功能和普遍存在的第二信使，调节着广泛的细胞功能。先进的浓度测量方法、遗传实验、细胞命运追踪数据、单细胞成像和转录组学研究为其特定作用提供了信息，将信号整合到一系列机制中，这些机制决定了 HSC 的身份、谱系潜能、维持和自我更新。越来越多的证据表明，Ca 是 HSC 以前未被承认的特征之一，通过调节包括转录和表观遗传因子、Ca 依赖性激酶和线粒体生理学在内的多种因子，参与功能维持。线粒体是 HSC 功能的重要参与者，其对细胞需求的反应在很大程度上受到 Ca 信号的控制。最近的报告表明，线粒体 Ca 摄取也控制着 HSC 的命运。这些观察结果揭示了造血干细胞的生理特征，可以被利用来改善与 HSC 相关的疾病。在这篇综述中，我们讨论了目前关于造血干细胞中 Ca 的知识，重点讨论了其在 HSC 的增殖、自我更新和维持中的潜在作用，并讨论了未来的研究方向。
