Loose Matt, Swiers Gemma, Patient Roger
Institute of Genetics, University of Nottingham, Queen's Medical Centre, Nottingham, UK.
Curr Opin Hematol. 2007 Jul;14(4):307-14. doi: 10.1097/MOH.0b013e3281900eee.
We provide a summary of the temporal cascade of transcriptional networks giving rise to the hematopoietic stem cell (HSC) and controlling differentiation of the erythroid lineage from it. We focus on the mechanisms by which cell fate decisions are made and comment on recent developments and additions to the networks.
A role for an SCL/LMO2 complex in HSC emergence, as well as in subsequent erythroid differentiation, has received support. Connections between the transcriptional networks and signaling molecules are being made but more work is needed in this area. Evidence that transcriptional cross-antagonistic switches underlie the choice between lineage pathways is increasing, and we highlight how the dynamics of earlier lineage decisions can influence later ones. Mathematical models are being built and reveal a surprising degree of power in these simple motifs to explain lineage choices.
New links in the transcriptional networks underlying cell-fate decisions are constantly emerging, and their incorporation into the evolving networks will make mathematical modeling more precise in its predictions of cell behavior, which can be tested experimentally.
我们总结了导致造血干细胞（HSC）产生并控制其向红系谱系分化的转录网络的时间级联反应。我们重点关注细胞命运决定的机制，并对网络的最新进展和补充进行评论。
SCL/LMO2复合物在造血干细胞出现以及随后的红系分化中所起的作用得到了支持。转录网络与信号分子之间的联系正在建立，但该领域仍需更多研究。越来越多的证据表明转录交叉拮抗开关是谱系途径选择的基础，我们强调早期谱系决定的动态过程如何影响后期决定。数学模型正在构建中，这些简单基序在解释谱系选择方面展现出惊人的强大能力。
细胞命运决定所依据的转录网络中的新联系不断涌现，将它们纳入不断发展的网络将使数学模型对细胞行为的预测更加精确，而这可以通过实验进行验证。
