Zayas Jennifer, Spassov Danislav S, Nachtman Ronald G, Jurecic Roland
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Stem Cells Dev. 2008 Apr;17(2):343-53. doi: 10.1089/scd.2007.0101.
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.
c-kit受体在造血干细胞（HSCs）和多能祖细胞（MPPs）的自我更新及分化过程中发挥着至关重要的作用。我们发现，除了c-kit之外，小鼠多能HSC/MPP样细胞系EML还表达一种截短的细胞内形式的c-kit受体的转录本和蛋白质，称为tr-kit。值得注意的是，在细胞因子诱导HSC/MPP样细胞系EML分化为髓系红细胞谱系的过程中，tr-kit的转录本和蛋白质水平下调。这些发现促使我们分析tr-kit在纯化的小鼠胎肝和骨髓细胞群体中的表达情况，这些细胞群体包含长期重建造血（LTR）HSCs、短期重建造血（STR）HSCs、MPPs、谱系定向祖细胞和未成熟血细胞。值得注意的是，这些研究表明，与c-kit更广泛的表达不同，tr-kit仅在富含LTR-HSCs、STR-HSCs和MPPs的细胞群体中转录。另一方面，HSCs和MPPs存在频率低得多或完全不存在的细胞群体，即代表分化为淋巴系和髓系谱系更晚期阶段的细胞不表达tr-kit。tr-kit仅在更原始的富含HSC和MPP的细胞群体中与c-kit共表达这一观察结果，引发了一个令人兴奋的可能性，即tr-kit要么作为干细胞因子（SCF）/c-kit途径的一个新组分发挥作用，要么参与一个仅存在于HSC和MPPs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。
