Xie Rongfang, Li Miaomiao, Wang Xusheng, Liu Zhongjie
School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, 518107, China.
Department of Hemangioma and Vascular Malformation Surgery, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450003, China.
Cell Mol Life Sci. 2025 Jan 12;82(1):41. doi: 10.1007/s00018-024-05564-x.
Hair follicle (HF) development and pigmentation are complex processes governed by various signaling pathways, such as TGF-β and FGF signaling pathways. Nestin + (neural crest like) stem cells are also expressed in HF stem cells, particularly in the bulge and dermal papilla region. However, the specific role and differentiation potential of these Nestin-positive cells within the HF remain unclear, especially regarding their contribution to melanocyte formation and hair pigmentation. Bone morphogenetic protein 4 (BMP4), members of the TGFβ family, has been implicated in regulating HF growth, coloration, and related cellular behaviors. Its role in directing Nestin-positive cells toward a melanocytic lineage has yet to be fully explored. In this study, mouse HF organoids were constructed and shown to be an ideal model for studying HF growth and development in vitro. Using this model as a basis, we demonstrated that BMP4 controls HF coloration as well as its length, number, and even size. Furthermore, Nestin-positive cells in the HF-especially those in the bulge region-differentiate into melanocytes, which produce the pigments that give HF its color under BMP4 stimulation. The resulting increase in pigmentation within the mouse HF organoids underscores that BMP4 has a major regulatory role in the formation of melanocytes from Nestin-positive stem cells. This research provides insights into the cellular mechanisms underlying hair pigmentation and suggests potential therapeutic applications for pigmentation disorders.
毛囊（HF）的发育和色素沉着是由多种信号通路（如TGF-β和FGF信号通路）调控的复杂过程。巢蛋白阳性（神经嵴样）干细胞也在HF干细胞中表达，特别是在隆突和真皮乳头区域。然而，这些巢蛋白阳性细胞在HF内的具体作用和分化潜能仍不清楚，尤其是它们对黑素细胞形成和毛发色素沉着的贡献。骨形态发生蛋白4（BMP4）是TGFβ家族成员，已被证明与调节HF生长、色素沉着及相关细胞行为有关。其在引导巢蛋白阳性细胞向黑素细胞谱系分化方面的作用尚未得到充分研究。在本研究中，构建了小鼠HF类器官，并证明其是体外研究HF生长和发育的理想模型。以该模型为基础，我们证明BMP4可控制HF的色素沉着以及其长度、数量甚至大小。此外，HF中的巢蛋白阳性细胞，尤其是隆突区域的那些细胞，在BMP4刺激下分化为黑素细胞，黑素细胞产生赋予HF颜色的色素。小鼠HF类器官中色素沉着的增加突显了BMP4在巢蛋白阳性干细胞形成黑素细胞过程中具有主要调节作用。本研究为毛发色素沉着的细胞机制提供了见解，并为色素沉着障碍提示了潜在的治疗应用。
