Nature：细胞的“转分化”和“脱分化”
成熟分化的细胞类型是怎样被控制的、通过充分分化的细胞类型能够实现什么程度的发育弹性？这是发育生物学和干细胞研究中一个重要的、基础性的问题。这个领域的一个中心问题，即细胞是通过直接“转分化”（transdifferentiation）被直接重新编程为一种不同细胞类型的，还是在沿被称为“脱分化”（dedifferentiation）的另一条路径前进之前采取了一个向后的步骤而进入一种更不成熟的状态，由本期Nature上发表的一篇研究报告进行了解答。Cobaleda等人演示了在成熟B-淋巴瘤细胞转化成功能性T-细胞过程中的脱分化。Pax5（一个对于B-细胞分化和功能很重要的转录因子）的删除引起成熟B-细胞脱分化成能够产生T-细胞的先祖细胞。Pax5已知在癌症中也扮演一个角色，它的缺失能诱发由先祖细胞形成的淋巴瘤。
英文原文：
Nature 449, 473-477 (27 September 2007) | doi:10.1038/nature06159; Received 2 May 2007; Accepted 8 August 2007; Published online 12 September 2007
Conversion of mature B cells into T cells by dedifferentiation to uncommitted progenitors
César Cobaleda1,3, Wolfram Jochum2 & Meinrad Busslinger1
- Research Institute of Molecular Pathology, Vienna Biocenter, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria
- Department of Pathology, University Hospital, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland
- Present address: Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
Correspondence to: Meinrad Busslinger1 Correspondence and requests for materials should be addressed to M.B. (Email: busslinger@imp.ac.at).
Lineage commitment and differentiation to a mature cell type are considered to be unidirectional and irreversible processes under physiological conditions1. The commitment of haematopoietic progenitors to the B-cell lineage2, 3 and their development to mature B lymphocytes4, 5 critically depend on the transcription factor encoded by the paired box gene 5 (Pax5). Here we show that conditional Pax5 deletion in mice allowed mature B cells from peripheral lymphoid organs to dedifferentiate in vivo back to early uncommitted progenitors in the bone marrow, which rescued T lymphopoiesis in the thymus of T-cell-deficient mice. These B-cell-derived T lymphocytes carried not only immunoglobulin heavy- and light-chain gene rearrangements but also participated as functional T cells in immune reactions. Mice lacking Pax5 in mature B cells also developed aggressive lymphomas, which were identified by their gene expression profile as progenitor cell tumours. Hence, the complete loss of Pax5 in late B cells could initiate lymphoma development and uncovered an extraordinary plasticity of mature peripheral B cells despite their advanced differentiation stage.
相关报道:
- 众说风云 (已有0条评论)
