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人类嗅上皮中的体内和体外神经发生

In vivo and in vitro neurogenesis in human olfactory epithelium.

作者信息

Hahn Chang-Gyu, Han Li-Ying, Rawson Nancy E, Mirza Natasha, Borgmann-Winter Karin, Lenox Robert H, Arnold Steven E

机构信息

Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.

出版信息

J Comp Neurol. 2005 Mar 7;483(2):154-63. doi: 10.1002/cne.20424.

Abstract

The birth and differentiation of neurons have been extensively studied in the olfactory epithelium (OE) of rodents but not in humans. The goal of this study was to characterize cellular composition and molecular expression of human OE in vivo and in vitro. In rodent OE, there are horizontal basal cells and globose basal cells that are morphologically and functionally distinct. In human OE, however, there appears to be no morphological distinction among basal cells, with almost all cells having round cell bodies similar to rodent globose basal cells. Unlike the case in rodents, human basal cells, including putative neuronal precursors, express p75NGFR, suggesting a distinctive role for p75NGFR in human OE neurogenesis. Molecular expression of neuronal cells during differentiation in human OE grossly follows that in rodents. However, the topographical organization of immature and mature ORNs in human OE differs from that of rodents, in that immature and mature ORNs in humans are dispersed throughout the OE, whereas rodent counterparts have a highly laminar organization. These observations together suggest that the birth and differentiation of neuronal cells in human OE differ from those in rodents. In OE explant culture, neuronal cells derived from human OE biopsy express markers for immature and mature neurons, grossly recapitulating neuronal differentiation of olfactory neurons in vivo. Furthermore, small numbers of cells are doubly label for bromodeoxyuridine and olfactory marker protein, indicating that neuronal cells born in vitro reach maturity. These data highlight species-related differences in OE development and demonstrate the utility of explant culture for experimental studies of human neuronal development.

摘要

神经元的产生和分化在啮齿动物的嗅觉上皮(OE)中已得到广泛研究,但在人类中尚未有相关研究。本研究的目的是在体内和体外对人类OE的细胞组成和分子表达进行表征。在啮齿动物的OE中,存在形态和功能上不同的水平基底细胞和球状基底细胞。然而,在人类OE中,基底细胞之间似乎没有形态学差异,几乎所有细胞都具有圆形细胞体,类似于啮齿动物的球状基底细胞。与啮齿动物不同,人类基底细胞,包括假定的神经元前体,表达p75NGFR,这表明p75NGFR在人类OE神经发生中具有独特作用。人类OE中神经元细胞在分化过程中的分子表达总体上与啮齿动物相似。然而,人类OE中未成熟和成熟嗅觉受体神经元(ORN)的拓扑组织与啮齿动物不同,人类中未成熟和成熟的ORN分散在整个OE中,而啮齿动物的对应物具有高度分层的组织。这些观察结果共同表明,人类OE中神经元细胞的产生和分化与啮齿动物不同。在OE外植体培养中,源自人类OE活检的神经元细胞表达未成熟和成熟神经元的标志物,总体上概括了体内嗅觉神经元的神经元分化。此外,少量细胞同时被溴脱氧尿苷和嗅觉标记蛋白双重标记,表明体外产生出生的神经元细胞能够成熟。这些数据突出了OE发育中与物种相关的差异,并证明了外植体培养在人类神经元发育实验研究中的实用性。

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