p53-mediated hematopoietic stem and progenitor cell competition.
p53-mediated hematopoietic stem and progenitor cell competition.
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DOI：
10.1016/j.stem.2010.03.002
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发表时间：
2010-04-02
期刊：
影响因子：
23.9
通讯作者：
Medzhitov R
中科院分区：
文献类型：
--
作者：
Bondar T;Medzhitov R
细胞竞争最初在果蝇中被描述为选择最适合的细胞的过程。它可能在所有后生动物的组织稳态中起重要作用，但对其在哺乳动物中的作用和调节知之甚少。使用遗传嵌合小鼠模型和骨髓嵌合体，我们在这里描述了一种细胞竞争的形式，选择最少受损的细胞。这种竞争由p53控制，但与经典的p53介导的DNA损伤反应不同：它持续数月，对造血干细胞和祖细胞具有特异性，并且取决于竞争细胞中p53的相对水平而不是绝对水平。竞争似乎是介导的非细胞自主诱导生长停滞和衰老相关的基因表达的竞争细胞具有较高的p53活性。p53介导的这种类型的细胞竞争可能潜在地有助于初期癌细胞的克隆扩增。
Cell competition was originally described in Drosophila as a process for selection of the fittest cells. It is likely to play an important role in tissue homeostasis in all metazoans, but little is known about its role and regulation in mammals. Using genetic mosaic mouse models and bone marrow chimeras, we describe here a form of cell competition that selects for the least damaged cells. This competition is controlled by p53 but is distinct from the classical p53-mediated DNA damage response: it persists for months, is specific to the hematopoietic stem and progenitor cells, and depends on the relative rather than absolute level of p53 in competing cells. The competition appears to be mediated by a non-cell autonomous induction of growth arrest and senescence-related gene expression in outcompeted cells with higher p53 activity. p53-mediated cell competition of this type could potentially contribute to the clonal expansion of incipient cancer cells.
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