Recent experiments revealed that both IR stress and DMBA treatment increase the stem cell factor (SCF) expression level at the secondary hair germ and dermal papillae. However, IR stress causes hair graying due to the damaged melanocytic stem cells (McSCs), while DMBA treatment causes the hyperpigmentation of coat hair in the dorsal skin. This result provokes two important questions;
1) SCF/c-KIT signal is the only signal pathway to maintain the differentiation of immature melanocytes also referred to as melanoblasts or McSCs?
2) What is responsible for the paradoxical phenotype between enhanced SCF expression level and coat hair color?
- Are these data unpublished? I can't see any papers about this in a quick search.
- What are you using IR to mean here? Ionizing radiation? Infrared?
(1) - not sure what you mean by a pathway maintaining differentiation. SCF/KIT signalling can promote proliferation and/or survival (under different conditions) of both melanoblasts and melanocytes.
If you really mean survival: other factors including BCL2 and notch signalling are reported to promote survival of McSCs.
Or do you mean, pathways that prevent McSCs or melanoblasts differentiating into melanocytes? SCF can do that under some conditions; Notch has been suggested to do that, and ASIP.
(2) Guessing IR might be ionizing radiation, are these differences independent of dose or could it be that both IR and DMBA could produce both effects at different doses? There might be an involvement of p53, which is activated by DNA damage. p53 in keratinocytes can stimulate melanogenesis through SCF and MSH secretion, as G Barsh and others showed; or under other conditions p53 (in cells generally) can cause apoptosis.
Thank you for your helpful comments, Dr. Dorothy C Bennett.
This experimental data is under revised period now.
IR herein means ionizing radiation at the dose of 4-5 Gy.
1) Survival is the anti-apoptotic capacity due to Bcl-2 and I am also devoted in the normal differentiation of McSCs. I will check the Notch activity by performing q-PCR to reveal the transcription level of Hey and Hes. Also, I will try the F-IHC with Notch ICD antibody merged with SCF-GFP knock-in mice. Thank in advance for your comment!
2) According to q-PCR, both of IR and DMBA treatment increases SCF mRNA level up to two-fold as compared with control. I have already made the mating with Dct-Cre;p53(fx/fx); SCF-GFP-KI, but contrary to my expectations, there was no much difference depending on p53 expression. CDK such as p21 might not only induce cellular senescence (cell cycle arrest) but also influence on the paradoxical phenotype.
Anyway, I have to investigate into the molecular machinery why I cannot detect positive correlation of SCF expression and coat hair color between IR and DMBA treatment, both of which increases SCF expression, but induces hair graying and hyper-pigmentation, respetively.
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