PRE-COMMITMENT REGULATION OF CELL DIFFERENTIATION

这些研究调查了子宫内膜癌中细胞分化的控制。 体外未定植的人类前体细胞。该实验系统是 分化双能细胞系HL-60人早幼粒白血病细胞系 经历髓系或单核细胞终末细胞的细胞 差异化。以往关于髓系分化的研究表明， 细胞对感应信号的反应包括两种中间状态， 预先承诺和承诺，发生在表型终端之前 细胞的分化。承诺是一个点，在这个点之后 诱导信号的缺失并不能阻止随后的细胞分化。 在其他实验系统中也发现了这样一个点的存在， 也是。相反，预先承诺是一种较早的状态，其中移除 诱导剂导致随后不能表型的细胞 分化或生长停滞。预承诺单元格只需要 短期后续暴露于诱导剂以诱导表型分化 和增长停滞。预承诺状态是不稳定的，并且与 核膜结构和细胞质的特征性变化 蛋白质。这些数据表明，预先承诺是有效的 一种故障安全状态。响应于诱导信号，前体细胞被 第一次开到这个状态。如果它接收到后续信号，则它是 被驱使去承诺。如果不是，它就会恢复到最初的幼稚状态。这个 因此，预先承诺状态作为可识别的监管机构具有重要意义 州政府。这项研究的目的是确定这种状态是否 可概括为单核细胞谱系，并确定关系 在髓系预承诺状态和单核细胞状态之间。我们 将决定细胞是否进展到相同的终末状态 分化是由于不同的诱导剂涉及相同的 中间预先承诺状态，如果预先承诺监管状态 分化是特定于谱系的，如果细胞质的变化 蛋白质和/或核膜结构与 髓系分化过程中的预承诺状态也是常见的 单核细胞分化过程。(M)

These studies investigate the control of cell differentiation in an in vitro uncommitted human precursor cell. The experimental system is the HL-60 human promyelocytic leukemia cell line, a differentially bipotent cell which undergoes either myeloid or monocytic terminal cell differentiation. Previous studies on myeloid differentiation showed that cellular response to an induction signal involved two intermediate states, pre-commitment and commitment, occurring before phenotypic terminal differentiation of the cells. Commitment is the point after which removal of the inducing signal does not prevent subsequent cell differentiation. The existence of such a point has been found in other experimental systems, too. Pre-commitment, in contrast, is an earlier state where removal of the inducer results in cells which fail to subsequently phenotypically differentiate or growth arrest. Pre-commitment cells require only an abbreviated subsequent exposure to inducer to phenotypically differentiate and growth arrest. The pre-commitment state is labile and associated with characteristic changes in nuclear envelope structure and cytoplasmic proteins. The data suggest a model in which pre-commitment is effectively a fail-safe state. In response to an inducing signal, a precursor cell is first driven to this state. If it receives a subsequent signal, it is driven to commitment. If not, it reverts to its initial naive state. The pre-commitment state is thus of significance as an identifiable regulatory state. The object of this research is to detemine if this state is generalizable to the monocytic lineage and to determine the relationship between the myeloid lineage pre-commitment state and the monocytic one. We will determine if cellular progression to the same state of terminal differentiation is due to different inducers involving the same intermediate pre-commitment state, if the pre-commitment regulatory state differentiation is lineage specific, and if the changes in cytoplasmic proteins and/or nuclear membrane structure are associated with the pre-commitment state during myeloid differentiation also common to the course of monocytic differentiation. (M)