Rothenberg Ellen V, Anderson Michele K
Division of Biology 156-29, California Institute of Technology, Pasadena 91125, USA.
Dev Biol. 2002 Jun 1;246(1):29-44. doi: 10.1006/dbio.2002.0667.
The complex spectrum of cell types produced in mammalian hematopoiesis can be understood as the output of highly combinatorial transcription factor action. The generation of multiple diverse combinations of transcription factors from the common starting state of the hematopoietic stem cell must be explained through the cross-regulatory interactions of these transcription factors at several levels. Here, the operation of such a network is addressed through a focus on murine T cell development, where we have recently established regulatory linkages between GATA-3 and PU.1 and multiple other factors essential to this differentiation pathway. The action of both essential/rate-limiting factors and factors with effects that shift qualitatively with dose and time of action can be traced through the regulatory interaction network. Hypothetical models are proposed to indicate the network nodes that are differentially activated in normal T cell lineage progression and in cells diverted to other potential fates.
哺乳动物造血过程中产生的复杂细胞谱系可被理解为高度组合性转录因子作用的输出结果。造血干细胞的共同起始状态产生多种不同转录因子组合的现象，必须通过这些转录因子在多个层面的交叉调节相互作用来解释。在此，我们通过聚焦小鼠T细胞发育来探讨这样一个网络的运作，近期我们已在GATA-3与PU.1以及该分化途径中其他多个关键因子之间建立了调控联系。通过调控相互作用网络，可以追踪必需/限速因子以及作用效果随剂量和作用时间发生质性变化的因子的作用。我们提出了假设模型，以指明在正常T细胞谱系进展以及转向其他潜在命运的细胞中差异激活的网络节点。
