Integrative Immunobiology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States.
Integrative Immunobiology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States.
Adv Immunol. 2024;161:85-108. doi: 10.1016/bs.ai.2024.03.003. Epub 2024 Mar 21.
Hematopoiesis, a process which generates blood and immune cells, changes significantly during mammalian development. Definitive hematopoiesis is marked by the emergence of long-term hematopoietic stem cells (HSCs). Here, we will focus on the post-transcriptional differences between fetal liver (FL) and adult bone marrow (ABM) HSCs. It remains unclear how or why exactly FL HSCs transition to ABM HSCs, but we aim to leverage their differences to revive an old idea: in utero HSC transplantation. Unexpectedly, the expression of certain RNA-binding proteins (RBPs) play an important role in HSC specification, and can be employed to convert or reprogram adult HSCs back to a fetal-like state. Among other features, FL HSCs have a broad differentiation capacity that includes the ability to regenerate both conventional B and T cells, as well as innate-like or unconventional lymphocytes such as B-1a and marginal zone B (MzB) cells. This chapter will focus on RNA binding proteins, namely LIN28B and IGF2BP3, that are expressed during fetal life and how they promote B-1a cell development. Furthermore, this chapter considers a potential clinical application of synthetic co-expression of LIN28B and IGF2BP3 in HSCs.
造血是一个产生血液和免疫细胞的过程，在哺乳动物的发育过程中会发生显著变化。确定性造血的标志是出现长期造血干细胞（HSCs）。在这里，我们将重点关注胎儿肝脏（FL）和成人骨髓（ABM）HSCs 之间的转录后差异。目前尚不清楚 FL HSCs 如何或为什么会过渡到 ABM HSCs，但我们旨在利用它们的差异来重新审视一个旧观念：子宫内 HSC 移植。出人意料的是，某些 RNA 结合蛋白（RBPs）的表达在 HSC 特化中起着重要作用，并可用于将成人 HSCs 转化或重新编程为类似胎儿的状态。除其他特征外，FL HSCs 具有广泛的分化能力，包括再生常规 B 和 T 细胞以及先天样或非常规淋巴细胞（如 B-1a 和边缘区 B（MzB）细胞）的能力。本章将重点介绍在胎儿期表达的 RNA 结合蛋白，即 LIN28B 和 IGF2BP3，以及它们如何促进 B-1a 细胞的发育。此外，本章还考虑了在 HSCs 中人工共表达 LIN28B 和 IGF2BP3 的潜在临床应用。
