PMID- 32957735 OWN - NLM STAT- MEDLINE DCOM- 20210324 LR - 20210324 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 9 IP - 9 DP - 2020 Sep 17 TI - How Relevant Are Bone Marrow-Derived Mast Cells (BMMCs) as Models for Tissue Mast Cells? A Comparative Transcriptome Analysis of BMMCs and Peritoneal Mast Cells. LID - 10.3390/cells9092118 [doi] LID - 2118 AB - 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. FAU - Akula, Srinivas AU - Akula S AUID- ORCID: 0000-0001-6628-1640 AD - Department of Cell and Molecular Biology, Uppsala University, The Biomedical Center, Box 596, SE-751 24 Uppsala, Sweden. FAU - Paivandy, Aida AU - Paivandy A AD - Department of Medical Biochemistry and Microbiology, Uppsala University, The Biomedical Center, Box 589, SE-751 23 Uppsala, Sweden. FAU - Fu, Zhirong AU - Fu Z AD - Department of Cell and Molecular Biology, Uppsala University, The Biomedical Center, Box 596, SE-751 24 Uppsala, Sweden. FAU - Thorpe, Michael AU - Thorpe M AD - Department of Cell and Molecular Biology, Uppsala University, The Biomedical Center, Box 596, SE-751 24 Uppsala, Sweden. FAU - Pejler, Gunnar AU - Pejler G AD - Department of Medical Biochemistry and Microbiology, Uppsala University, The Biomedical Center, Box 589, SE-751 23 Uppsala, Sweden. AD - Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Box 7011, SE-75007 Uppsala, Sweden. FAU - Hellman, Lars AU - Hellman L AD - Department of Cell and Molecular Biology, Uppsala University, The Biomedical Center, Box 596, SE-751 24 Uppsala, Sweden. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200917 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (Biomarkers) RN - 0 (Complement C2) RN - 0 (Gfra2 protein, mouse) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor Receptors) RN - 0 (Homeodomain Proteins) RN - 0 (Milr1 protein, mouse) RN - 0 (Mrg1 protein, mouse) RN - 0 (Mrgprb2 protein, mouse) RN - 0 (Proto-Oncogene Proteins c-myb) RN - 0 (Receptors, G-Protein-Coupled) RN - 0 (Receptors, Immunologic) RN - 0 (Receptors, Interleukin-3) RN - 0 (TARM1 protein, mouse) RN - EC 3.4.21.- (Serine Endopeptidases) RN - EC 3.4.21.- (mast cell protease 4) RN - EC 3.4.24.- (ADAMTS9 Protein) RN - EC 3.4.24.- (Adamts9 protein, mouse) RN - EC 4.1.1.22 (Histidine Decarboxylase) SB - IM MH - ADAMTS9 Protein/genetics/metabolism MH - Animals MH - B-Lymphocytes/cytology/*metabolism MH - Biomarkers/metabolism MH - Bone Marrow Cells/cytology/*metabolism MH - Complement C2/genetics/metabolism MH - Female MH - Gene Expression Regulation MH - Glial Cell Line-Derived Neurotrophic Factor Receptors/genetics/metabolism MH - Histidine Decarboxylase/genetics/metabolism MH - Homeodomain Proteins/genetics/metabolism MH - Macrophages/cytology/*metabolism MH - Mast Cells/cytology/*metabolism MH - Mice MH - Mice, Inbred BALB C MH - Organ Specificity MH - Peritoneum/cytology/*metabolism MH - Proto-Oncogene Proteins c-myb/genetics/metabolism MH - Receptors, G-Protein-Coupled/genetics/metabolism MH - Receptors, Immunologic/genetics/metabolism MH - Receptors, Interleukin-3/genetics/metabolism MH - Serine Endopeptidases/genetics/metabolism MH - *Transcriptome PMC - PMC7564378 OTO - NOTNLM OT - FcepsilonRI OT - chymase OT - heparin OT - histamine OT - in vitro model OT - mRNA OT - mast cell OT - serine protease OT - transcriptome OT - tryptase COIS- The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. EDAT- 2020/09/23 06:00 MHDA- 2021/03/25 06:00 PMCR- 2020/09/01 CRDT- 2020/09/22 01:03 PHST- 2020/07/29 00:00 [received] PHST- 2020/09/14 00:00 [revised] PHST- 2020/09/16 00:00 [accepted] PHST- 2020/09/22 01:03 [entrez] PHST- 2020/09/23 06:00 [pubmed] PHST- 2021/03/25 06:00 [medline] PHST- 2020/09/01 00:00 [pmc-release] AID - cells9092118 [pii] AID - cells-09-02118 [pii] AID - 10.3390/cells9092118 [doi] PST - epublish SO - Cells. 2020 Sep 17;9(9):2118. doi: 10.3390/cells9092118.