Brown Geoffrey, Hughes Philip J, Michell Robert H, Rolink Antonius G, Ceredig Rod
Division of Immunity and Infection, The Medical School, Edgbaston, Birmingham B15 2TT, UK.
Trends Immunol. 2007 Oct;28(10):442-8. doi: 10.1016/j.it.2007.07.007. Epub 2007 Sep 7.
Analysis of hematopoietic development has for decades been central to understanding lineage diversification. Some models consider hematopoietic commitment to be random, and branching lineage maps often include an early myeloid or lymphoid bifurcation. However, the existence of joint lymphoid or myeloid intermediate progenitors argues against both. One of us earlier proposed the sequential determination (SD) model, which features a limited and stepwise set of binary choices across the full hematopoietic spectrum. This model arose from observations that hematopoietic progenitors show preferences for particular associations of lineage potentials--indicating that these linked fates are neighbours developmentally. An updated SD model complemented by several recently recognized processes--spatiotemporal fluctuations in transcription factor concentrations, asymmetric cell division, and Notch signalling--still offers a sound summary of hematopoiesis.
几十年来，造血发育分析一直是理解谱系多样化的核心。一些模型认为造血定向是随机的，分支谱系图通常包括早期髓系或淋巴系分支。然而，联合淋巴系或髓系中间祖细胞的存在对这两种观点都提出了质疑。我们中的一人早些时候提出了顺序决定（SD）模型，该模型的特点是在整个造血谱系中存在一组有限且逐步的二元选择。这个模型源于这样的观察结果：造血祖细胞对特定的谱系潜能组合表现出偏好，这表明这些相关的命运在发育上是相邻的。一个由几个最近认识到的过程——转录因子浓度的时空波动、不对称细胞分裂和Notch信号传导——补充的更新的SD模型，仍然为造血提供了一个合理的总结。
