Multipotent Peripheral Glial Cells Generate Neuroendocrine Cells of the Adrenal Medulla

Cells producing adrenalin are largely derived from nerve-associated Schwann cell precursors via an intermediate progenitor “bridge” cell. We demonstrate that large numbers of chromaffin cells arise from peripheral glial stem cells, termed Schwann cell precursors (SCPs) SCPs migrate along the visceral motor nerve to the vicinity of the forming adrenal gland where they detach from the nerve and form post-synaptic neuroendocrine chromaffin cells. An intricate molecular logic drives two sequential phases of gene expression, one unique for a distinct transient cellular state and another for cell-type specification. Subsequently, these programs downregulate SCP- and upregulate chromaffin-cell-gene networks. The adrenal medulla forms through limited cell expansion and requires the recruitment of numerous SCPs. Thus, peripheral nerves serve as a stem cell niche for neuroendocrine system development.

产生肾上腺素的细胞主要通过一类充当中间祖细胞“桥梁”的细胞，源自与神经相关的雪旺细胞前体（Schwann cell precursors）。本研究证实，大量嗜铬细胞（chromaffin cells）源自被称为雪旺细胞前体（Schwann cell precursors, SCPs）的外周胶质干细胞。雪旺细胞前体沿内脏运动神经迁移至正在发育的肾上腺附近，随后脱离神经并分化为突触后神经内分泌嗜铬细胞。一套复杂的分子调控逻辑驱动了两个连续的基因表达阶段：一个对应独特的瞬时细胞状态，另一个则参与细胞类型特化。随后，这些基因表达程序会下调雪旺细胞前体相关基因网络，并上调嗜铬细胞相关基因网络。肾上腺髓质的形成依赖于有限的细胞扩增，并需要招募大量雪旺细胞前体。由此可见，外周神经可作为神经内分泌系统发育的干细胞龛（stem cell niche）。