The transcription factor profile of human mast cells in comparison with monocytes and granulocytes

Abstract

Expression profiles of mRNAs and proteins for various transcription factors were determined for human skin mast cells (sMCs), leukemic HMC-1 MCs, monocytes and granulocytes. By quantitative RT-PCR, sMCs expressed lower levels of c-fos, PU.1, C/EBPalpha, and C/EBPepsilon than monocytes and granulocytes, but higher levels of MITF, SCL, GATA-1 and GATA-2. At the protein level, MITF, SCL, GATA-2, Elf-1 and c-fos were clearly detectable in sMCs. With the exception of c-fos, these proteins were absent or expressed only slightly in monocytes and granulocytes. The expression of NF-E2p45, GATA-1, PU.1, Ets-1, C/EBPalpha and C/EBPepsilon was below the detection limit in sMCs, but detectable in other myelocytes. The high expression of SCL and GATA-2 in sMCs is reminiscent of stem cells. The absence of C/EBPvarepsilon in sMCs, but strong expression in HMC-1, suggests it may impair MC maturation. In summary, mature human MCs can be characterized as C/EBPalpha(low), C/EBPvarepsilon-, PU.1(low), GATA-1(low), GATA-2+, SCL+, MITF(high).

Mast cell lineage diversion of T lineage precursors by the essential T cell transcription factor GATA-3

“…Balanced activity of PU.1 and GATA factors is known to be required, along with Mitf and possibly SCL, and roles of GATA-2 and GATA-1 in this process can now be distinguished 27,[38][39][40] . However, it has remained obscure whether mast cells are 'myeloid' or in a distinct class of their own.…”

Redefinition of the human mast cell transcriptome by deep-CAGE sequencing

“…We employed hierarchical clustering to identify patterns of genes coexpressed with significant TFs (see Babina et al 36 and references therein) and with the newly discovered marker MRGPRX2.…”

“…Because BMPR activation stimulates lineagespecific transcription factors in HSCs, 36 we tested the impact of BMPR stimulation on the expression of markers and transcription factors (TFs) of the lineage. 37 Fc«RIa and GATA-1 transcripts were selectively increased by BMP signaling ( Figure 1A), probably through direct activation of lineage-specific TFs by Smads.…”

KIT signaling regulates MITF expression through miRNAs in normal and malignant mast cell proliferation

“…8 It is expressed in normal human skin mast cells, as well as human mastocytosis; however, it is not highly expressed in human monocytes or granulocytes. 9,10 Mice with a deficiency of MITF display an absence of mast cells, and MITF-deficient cultured mast cells appear immature and do not express genes critical for mast cell function. 11 The in vivo and in vitro mast cell and melanocyte phenotype of Mitf mutant mice is strikingly similar to that of SCF or KIT-deficient mice.…”