Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons.
Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons.
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DOI：
10.1002/cne.23653
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发表时间：
2015-01-01
影响因子：
2.5
通讯作者：
Hare, Joshua M.
中科院分区：
文献类型：
--
作者：
Goldstein, Bradley J.;Goss, Garrett M.;Hatzistergos, Konstantinos E.;Rangel, Erika B.;Seidler, Barbara;Saur, Dieter;Hare, Joshua M.
嗅觉上皮含有化学感觉神经元，这些神经元将气味信息从鼻子传递到大脑。在成年哺乳动物中，嗅觉上皮是一个独特的强健的神经增殖区，由于生发基底细胞的存在，它具有补充神经元和非神经元种群的能力。这些生发层的干细胞和祖细胞，以及它们的调节机制，仍然没有完全确定。在这里，我们表明，表达c-Kit的祖细胞是维持成人神经上皮所必需的，c-Kit是一种受体酪氨酸激酶，标志着各种胚胎组织中的干细胞。小鼠遗传命运图谱分析表明，从胚胎角度看，c-Kit(+)群体有助于嗅神经发生。在正常周转的成人中，c-Kit(+)祖细胞(Ck PC)活性相对稀少。然而，在实验诱导的神经上皮损伤后，CKPC被激活，从而重建神经元群体。偶尔也会发现非神经性细胞起源于CKPC。此外，利用时间控制的白喉毒素A表达，选择性地耗尽ck PC群体，导致实验性损伤后神经再生的失败。对这一模型的分析表明，大多数CKPC存在于球状基底细胞群中，并在水平基底细胞的下游起作用，水平基底细胞可以作为干细胞。嗅觉维持中对嗅觉c-Kit表达前体细胞的需求的鉴定为成人嗅觉神经发生的机制提供了新的见解。此外，我们还定义了一个重要的、以前未被发现的成人c-Kit活性位点。
The olfactory epithelium houses chemosensory neurons, which transmit odor information from the nose to the brain. In adult mammals, the olfactory epithelium is a uniquely robust neuroproliferative zone, with the ability to replenish its neuronal and non-neuronal populations due to the presence of germinal basal cells. The stem and progenitor cells of these germinal layers, and their regulatory mechanisms, remain incompletely defined. Here we show that progenitor cells expressing c-Kit, a receptor tyrosine kinase marking stem cells in a variety of embryonic tissues, are required for maintenance of the adult neuroepithelium. Mouse genetic fate-mapping analyses show that embryonically, a c-Kit (+) population contributes to olfactory neurogenesis. In adults under conditions of normal turnover, there is relatively sparse c-Kit (+) progenitor cell (ckPC) activity. However, after experimentally induced neuroepithelial injury, ckPCs are activated such that they reconstitute the neuronal population. There are also occasional non-neuronal cells found to arise from ckPCs. Moreover, the selective depletion of the ckPC population, utilizing temporally controlled targeted diphtheria toxin A expression, results in failure of neurogenesis after experimental injury. Analysis of this model indicates that most ckPCs reside among the globose basal cell populations and act downstream of horizontal basal cells, which can serve as stem cells. Identification of the requirement for olfactory c-Kit expressing progenitors in olfactory maintenance provides new insight into the mechanisms involved in adult olfactory neurogenesis. Additionally, we define an important and previously unrecognized site of adult c-Kit activity.
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影响因子：
6.1
作者：
Bergman, U;Östergren, A;Brittebo, EB
通讯作者：
Brittebo, EB
影响因子：
4.6
作者：
Gokoffski, Kimberly K.;Wu, Hsiao-Huei;Calof, Anne L.
通讯作者：
Calof, Anne L.
影响因子：
16.2
作者：
Fletcher RB;Prasol MS;Estrada J;Baudhuin A;Vranizan K;Choi YG;Ngai J
通讯作者：
Ngai J
影响因子：
2.5
作者：
Guo, Zhen;Packard, Adam;Krolewski, Richard C.;Harris, Margaret T.;Manglapus, Glen L.;Schwob, James E.
通讯作者：
Schwob, James E.
影响因子：
16.2
作者：
CALOF, AL;CHIKARAISHI, DM
通讯作者：
CHIKARAISHI, DM