Gameiro Juliana Gutschow, Hintschich Constantin A, Dekeyser Agnès, Hox Valérie, Schwob James E, Holbrook Eric H, Fornazieri Marco Aurélio, Lin Brian
Department of Clinical Surgery, State University of Londrina, Paraná, Londrina, Brazil; Health Sciences Graduate Program, State University of Londrina, Paraná, Londrina, Brazil; Department of Developmental, Molecular and Chemical Biology, Tufts University Graduate School of Biomedical Sciences, Boston, MA 02111, USA.
Department of Developmental, Molecular and Chemical Biology, Tufts University Graduate School of Biomedical Sciences, Boston, MA 02111, USA; Department of Otolaryngology - Head & Neck Surgery, Massachusetts Eye and Ear, Boston, MA, USA; Department of Otorhinolaryngology, Regensburg University Hospital, Regensburg, Germany; Department of Ophthalmology, Ludwig Maximilians University Munich, Munich, Germany.
Cell Rep Methods. 2025 Jun 16;5(6):101055. doi: 10.1016/j.crmeth.2025.101055. Epub 2025 May 28.
The olfactory epithelium contains two basal stem cell populations that facilitate the usually life-long ability for neuronal regeneration that is required for maintaining our sense of smell. Horizontal basal cells (HBCs) are generally quiescent and only become active after direct injury to the epithelium that eliminates more than just the olfactory sensory neurons (OSNs). Globose basal cells (GBCs) lie apical to HBCs and are solely responsible for the generation of olfactory neurons in the undamaged epithelium. Understanding how these two neurogenic stem cell populations are regulated as OSNs are replenished is hampered by a lack of robust culture models. Here, we report the development of a 3D mouse organoid model that recapitulates the neurogenic cascade, forming immature OSNs while maintaining both HBCs and GBCs in culture. We use this model to demonstrate that, despite their relative quiescence, HBCs form a critical niche for the emergence and composition of the organoid.
嗅觉上皮包含两个基底干细胞群体，它们促进了神经元再生这一通常终身具备的能力，而这种能力是维持我们嗅觉所必需的。水平基底细胞（HBCs）通常处于静止状态，只有在上皮受到直接损伤且不仅仅消除嗅觉感觉神经元（OSNs）时才会变得活跃。球状基底细胞（GBCs）位于HBCs的顶端，并且是未受损上皮中嗅觉神经元产生的唯一负责者。由于缺乏强大的培养模型，了解在OSNs得到补充时这两个神经源性干细胞群体是如何被调控的受到了阻碍。在此，我们报告了一种3D小鼠类器官模型的开发，该模型概括了神经发生级联反应，在培养中形成未成熟的OSNs，同时维持HBCs和GBCs。我们使用这个模型来证明，尽管HBCs相对静止，但它们为类器官的出现和组成形成了关键的生态位。
