Murine hematopoietic stem cells and multipotent progenitors express truncated intracellular form of c-kit receptor.
Murine hematopoietic stem cells and multipotent progenitors express truncated intracellular form of c-kit receptor.
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小鼠造血干细胞和多能祖细胞表达截短的细胞内形式的 c-kit 受体。
DOI：
10.1089/scd.2007.0101
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发表时间：
2008
影响因子：
4
通讯作者：
Jurecic,Roland
中科院分区：
文献类型：
--
作者：
Zayas,Jennifer;Spassov,DanislavS;Nachtman,RonaldG;Jurecic,Roland
c-kit受体在造血干细胞（hsc）和多能祖细胞（mpp）的自我更新和分化中起着重要作用。我们发现除了c-kit外，小鼠多能HSC/ mpp样细胞系EML还表达一种截断的细胞内c-kit受体的转录物和蛋白质，称为tr-kit。值得注意的是，在细胞因子诱导的HSC/ mpp样细胞系EML向髓系分化过程中，tr-kit转录物和蛋白水平下调。这些发现促使我们分析了含有长期再生（LTR）造血干细胞、短期再生（STR）造血干细胞、mpp、谱系承诺祖细胞和未成熟血细胞的纯化小鼠胎肝和骨髓细胞群中tr-kit的表达。值得注意的是，这些研究表明，与c-kit更广泛的表达相反，tr-kit仅在ltr - hsc、str - hsc和mpp富集的细胞群中转录。另一方面，造血干细胞和mpp出现频率较低或完全不存在的细胞群，向淋巴和髓系分化的更高级阶段的细胞不表达tr-kit。观察到tr-kit仅在更原始的HSC和mpp富集的细胞群中与c-kit共表达，这提出了一种令人兴奋的可能性，即tr-kit可能是干细胞因子(SCF)/c-kit途径的新组成部分，或者参与仅存在于HSC和mpp中的新信号通路。综上所述，这些发现需要对tr-kit进行功能表征，并分析其在HSC和多能祖细胞的自我更新、增殖和/或分化中的潜在作用。
The c-kit receptor plays a vital role in self-renewal and differentiation of hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs). We have discovered that besides c-kit, the murine multipotent HSC/MPP-like cell line EML expresses the transcript and protein for a truncated intracellular form of c-kit receptor, called tr-kit. Notably, the tr-kit transcript and protein levels were down-regulated during cytokine-induced differentiation of the HSC/MPP-like cell line EML into myeloerythroid lineages. These findings prompted us to analyze tr-kit expression in purified murine fetal liver and bone marrow cell populations containing long-term repopulating (LTR) HSCs, short-term repopulating (STR) HSCs, MPPs, lineage-committed progenitors, and immature blood cells. Remarkably, these studies have revealed that in contrast to more widespread expression of c-kit, tr-kit is transcribed solely in cell populations enriched for LTR-HSCs, STR-HSCs, and MPPs. On the other hand, cell populations in which HSCs and MPPs are either present at a much lower frequency or are absent altogether, cells representing more advanced stages of differentiation into lymphoid and myeloid lineages do not express tr-kit. The observation that tr-kit is co-expressed with c-kit only in more primitive HSC- and MPP-enriched cell populations raises an exciting possibility that tr-kit functions either as a new component of the stem cell factor (SCF)/c-kit pathway or is involved in a novel signaling pathway, present exclusively in HSC and MPPs. Taken together, these findings necessitate functional characterization of tr-kit and analysis of its potential role in the self-renewal, proliferation, and/or differentiation of HSC and multipotent progenitors.