CD34 defines melanocyte stem cell subpopulations with distinct regenerative properties

Melanocyte stem cells (McSCs) are the undifferentiated melanocytic cells of the mammalian hair follicle (HF) responsible for recurrent generation of a large number of differentiated melanocytes during each HF cycle. HF McSCs reside in both the CD34+ bulge/lower permanent portion (LPP) and the CD34- secondary hair germ (SHG) regions of the HF during telogen. Using Dct-H2BGFP mice, we separate bulge/LPP and SHG McSCs using FACS with GFP and anti-CD34 to show that these two subsets of McSCs are functionally distinct. Genome-wide expression profiling results support the distinct nature of these populations, with CD34- McSCs exhibiting higher expression of melanocyte differentiation genes and with CD34+ McSCs demonstrating a profile more consistent with a neural crest stem cell. In culture and in vivo, CD34- McSCs regenerate pigmentation more efficiently whereas CD34+ McSCs selectively exhibit the ability to myelinate neurons. CD34+ McSCs, and their counterparts in human skin, may be useful for myelinating neurons in vivo, leading to new therapeutic opportunities for demyelinating diseases and traumatic nerve injury.黑素细胞干细胞（Melanocyte stem cells, McSCs）是哺乳动物毛囊（hair follicle, HF）中的未分化黑素细胞，负责在每个毛囊周期中周期性再生大量分化后的黑素细胞。毛囊休止期时，McSCs同时定居于毛囊的CD34阳性隆突/下部永久区（bulge/lower permanent portion, LPP）与CD34阴性次级毛芽（secondary hair germ, SHG）两个区域。本研究通过Dct-H2BGFP小鼠，利用结合绿色荧光蛋白与抗CD34抗体的荧光激活细胞分选术（fluorescence-activated cell sorting, FACS）分离得到隆突/LPP与SHG亚型的McSCs，证实二者功能存在显著差异。全基因组表达谱分析结果验证了这两个细胞群的异质性：CD34阴性McSCs高表达黑素细胞分化相关基因，而CD34阳性McSCs的表达谱更符合神经嵴干细胞特征。无论是在体外培养还是体内环境中，CD34阴性McSCs均能更高效地修复色素沉着；而CD34阳性McSCs则可特异性介导神经元髓鞘化。CD34阳性McSCs及其在人类皮肤中的对应细胞群，有望用于体内神经元髓鞘修复，为脱髓鞘疾病与创伤性神经损伤的治疗带来新的临床机遇。