Lessons from early life: understanding development to expand stem cells and treat cancers.
Lessons from early life: understanding development to expand stem cells and treat cancers.
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DOI：
10.1242/dev.201070
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发表时间：
2022-10-15
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影响因子：
--
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造血干细胞（HSC）的自我更新是一个过程，是必不可少的发展和血液系统的稳态。自我更新扩增分裂，从一个单一的亲本HSC中产生两个子代HSC，可以用来为各种细胞和基因治疗创造大量的HSC，但同样的过程也是癌症等疾病中HSC异常扩增的驱动因素。虽然HSC首先在早期胚胎发育期间产生，但它们经历最大扩增的关键阶段和位置是在胎儿肝脏中，使该组织成为破译驱动HSC自我更新的分子的丰富数据来源。另一个同样有趣的阶段发生在出生后，即HSC迁移到骨髓几周后，此时HSC经历发育转变并进入更加休眠的状态。在发展过程中表征这些转变点是关键，无论是理解血液系统恶性肿瘤的演变，并制定方法，以促进HSC的扩张。在这篇聚焦文章中，我们概述了研究HSC发育给HSC扩增和转化医学领域带来的一些关键见解，其中许多见解为该领域的下一个重大突破奠定了基础。总结：本聚焦总结了我们对体内造血发育的理解如何应用于体外扩增造血干细胞，并帮助我们了解血癌的发展和可能的治疗。
Haematopoietic stem cell (HSC) self-renewal is a process that is essential for the development and homeostasis of the blood system. Self-renewal expansion divisions, which create two daughter HSCs from a single parent HSC, can be harnessed to create large numbers of HSCs for a wide range of cell and gene therapies, but the same process is also a driver of the abnormal expansion of HSCs in diseases such as cancer. Although HSCs are first produced during early embryonic development, the key stage and location where they undergo maximal expansion is in the foetal liver, making this tissue a rich source of data for deciphering the molecules driving HSC self-renewal. Another equally interesting stage occurs post-birth, several weeks after HSCs have migrated to the bone marrow, when HSCs undergo a developmental switch and adopt a more dormant state. Characterising these transition points during development is key, both for understanding the evolution of haematological malignancies and for developing methods to promote HSC expansion. In this Spotlight article, we provide an overview of some of the key insights that studying HSC development have brought to the fields of HSC expansion and translational medicine, many of which set the stage for the next big breakthroughs in the field. Summary: This Spotlight summarises how our understanding of haematopoietic development in vivo can be applied to expand haematopoietic stem cells in vitro and aid our understanding of the development, and possible treatment, of blood cancers.
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