Department of Cell and Molecular Biology, Uppsala University, The Biomedical Center, Box 596, SE-751 24 Uppsala, Sweden.
Department of Medical Biochemistry and Microbiology, Uppsala University, The Biomedical Center, Box 589, SE-751 23 Uppsala, Sweden.
Cells. 2020 Sep 17;9(9):2118. doi: 10.3390/cells9092118.
Bone marrow-derived mast cells (BMMCs) are often used as a model system for studies of the role of MCs in health and disease. These cells are relatively easy to obtain from total bone marrow cells by culturing under the influence of IL-3 or stem cell factor (SCF). After 3 to 4 weeks in culture, a nearly homogenous cell population of toluidine blue-positive cells are often obtained. However, the question is how relevant equivalents these cells are to normal tissue MCs. By comparing the total transcriptome of purified peritoneal MCs with BMMCs, here we obtained a comparative view of these cells. We found several important transcripts that were expressed at very high levels in peritoneal MCs, but were almost totally absent from the BMMCs, including the major chymotryptic granule protease Mcpt4, the neurotrophin receptor Gfra2, the substance P receptor Mrgprb2, the metalloprotease Adamts9 and the complement factor 2 (C2). In addition, there were a number of other molecules that were expressed at much higher levels in peritoneal MCs than in BMMCs, including the transcription factors Myb and Meis2, the MilR1 (Allergin), Hdc (Histidine decarboxylase), Tarm1 and the IL-3 receptor alpha chain. We also found many transcripts that were highly expressed in BMMCs but were absent or expressed at low levels in the peritoneal MCs. However, there were also numerous MC-related transcripts that were expressed at similar levels in the two populations of cells, but almost absent in peritoneal macrophages and B cells. These results reveal that the transcriptome of BMMCs shows many similarities, but also many differences to that of tissue MCs. BMMCs can thereby serve as suitable models in many settings concerning the biology of MCs, but our findings also emphasize that great care should be taken when extrapolating findings from BMMCs to the in vivo function of tissue-resident MCs.
骨髓来源的肥大细胞(BMMC)通常被用作研究 MC 在健康和疾病中作用的模型系统。这些细胞相对容易从总骨髓细胞中获得,通过在 IL-3 或干细胞因子(SCF)的影响下培养。在培养 3 到 4 周后,通常会获得一种近乎同质的甲苯胺蓝阳性细胞群体。然而,问题是这些细胞与正常组织 MC 有多么相关。通过比较纯化的腹腔 MC 和 BMMC 的全转录组,我们在这里获得了对这些细胞的比较观点。我们发现了一些重要的转录本,它们在腹腔 MC 中表达水平非常高,但在 BMMC 中几乎完全不存在,包括主要的糜蛋白酶颗粒蛋白酶 Mcpt4、神经生长因子受体 Gfra2、P 物质受体 Mrgprb2、金属蛋白酶 Adamts9 和补体因子 2(C2)。此外,还有一些其他分子在腹腔 MC 中的表达水平比在 BMMC 中高得多,包括转录因子 Myb 和 Meis2、MilR1(Allergin)、Hdc(组氨酸脱羧酶)、Tarm1 和 IL-3 受体α链。我们还发现许多在 BMMC 中高度表达但在腹腔 MC 中缺失或表达水平较低的转录本。然而,也有许多与 MC 相关的转录本在这两种细胞群体中的表达水平相似,但在腹腔巨噬细胞和 B 细胞中几乎不存在。这些结果表明,BMMC 的转录组显示出许多相似之处,但也与组织 MC 有许多差异。BMMC 可以在许多与 MC 生物学相关的环境中作为合适的模型,但我们的发现也强调,在将从 BMMC 中获得的发现外推到组织驻留 MC 的体内功能时,应格外小心。