CD164

更新于：2025-05-07

基本信息

别名

CD164、CD164 molecule、DFNA66

+ [6]

简介

Sialomucin that may play a key role in hematopoiesis by facilitating the adhesion of CD34(+) cells to the stroma and by negatively regulating CD34(+)CD38(lo/-) cell proliferation. Modulates the migration of umbilical cord blood CD133+ cells and this is mediated through the CXCL12/CXCR4 axis. May play an important role in prostate cancer metastasis and the infiltration of bone marrow by cancer cells. Promotes myogenesis by enhancing CXCR4-dependent cell motility. Positively regulates myoblast migration and promotes myoblast fusion into myotubes (By similarity).

关联

靶点

CD164

作用机制

CD164 inhibitors

在研机构-

原研机构

Eberhard Karls Universität Tübingen

在研适应症-

非在研适应症

肿瘤

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 CD164 相关的临床结果

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100 项与 CD164 相关的转化医学

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0 项与 CD164 相关的专利（医药）

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138

项与 CD164 相关的文献（医药）

2025-07-01·Biochemical Pharmacology

A novel long-acting recombinant follicle-stimulating hormone with hyperglycosylation exhibits improved pharmacokinetic and bioactivity on promoting follicle growth

Article

作者: Sun, Rongchen ; Yang, Xue ; Fan, Mingtao ; Wang, Ting ; Liu, Shang ; Zha, Zhengqi ; Hua, Zhen ; Yin, Hongping ; Du, Pei ; Yang, Meijia ; Yang, Youyou

Follicle-stimulating hormone (FSH) plays an indispensable role in fertility. Although Recombinant human FSH (rh-FSH) and long-acting FSH analogs, such as FSH-CTP (Elonva), have been used to treat infertility for many years. The need for multiple injections remains inconvenient and uncomfortable. Therefore, long-acting FSH with optimized metabolic properties and bioactivity is urgently required. In this study, we designed a new long-acting FSH by fusing mucin domain II of CD164 to the β-subunit of FSH, which was then combined with the α-subunit, generating FSH164. SDS-PAGE and a series of liquid chromatography analyses showed the changed physicochemical properties, in which the MW of FSH164 was 2-fold greater than that of rh-FSH, and exceeded the MW of Elonva. Glycosylation analysis via ultra-performance liquid chromatography (UPLC) demonstrated an abundance of O-glycans and N-glycans, with sialic acid in the extremities. In vitro experiments suggested that FSH164 improved efficacy in addressing the attenuation of downstream signaling activation associated with sustained-action FSH modifications compared with Elonva. Pharmacokinetic results suggested that, compared with Elonva, FSH164 had a 1.5-fold longer half-life in rats. Furthermore, increased activities in terms of ovary weight gain and superovulations were verified in rats and mice. In conclusion, the designed hyperglycosylated FSH164 exhibits a prolonged metabolic duration, with a single dose of FSH164 possessing bioactivity comparable to that of multiple rh-FSH injections, suggesting that it has great potential as a therapy for infertility.

2025-03-01·Cell Stem Cell

Human skeletal development and regeneration are shaped by functional diversity of stem cells across skeletal sites

Article

作者: Ambrosi, Thomas H ; Yang, George P ; Longaker, Michael T ; Wan, Derrick C ; Sokol, Jan ; Van Rysselberghe, Noelle L ; Gardner, Michael J ; Sinha, Rahul ; Hunt, Ethan J ; Wheeler, Erika E ; Wang, Yongheng ; Weissman, Irving L ; Liu, Daniel Dan ; Bishop, Julius A ; Wang, Yuting ; Weldon, Kelly C ; Leach, J Kent ; Wang, Aijun ; Taheri, Sahar ; Conley, Stephanie D ; Steininger, Holly M ; Sahoo, Debashis ; Neff, Norma F ; Zhao, Liming ; Morri, Maurizio ; Goodman, Stuart ; Chan, Charles K F ; Goodnough, L Henry ; Felix, Franco ; Murphy, Matthew P ; Lu, Wan-Jin ; Chen, Kun ; Koepke, Lauren S ; Hoover, Malachia Y ; Saiz, Augustine

The skeleton is one of the most structurally and compositionally diverse organ systems in the human body, depending on unique cellular dynamisms. Here, we integrate prospective isolation of human skeletal stem cells (hSSCs; CD45^-CD235a^-TIE2^-CD31^-CD146^-PDPN⁺CD73⁺CD164⁺) from ten skeletal sites with functional assays and single-cell RNA sequencing (scRNA-seq) analysis to identify chondrogenic, osteogenic, stromal, and fibrogenic subtypes of hSSCs during development and their linkage to skeletal phenotypes. We map the distinct composition of hSSC subtypes across multiple skeletal sites and demonstrate their unique in vivo clonal dynamics. We find that age-related changes in bone formation and regeneration disorders stem from a pathological fibroblastic shift in the hSSC pool. Utilizing a Boolean algorithm, we uncover gene regulatory networks that dictate differences in the ability of hSSCs to generate specific skeletal tissues. Importantly, hSSC lineage dynamics are pharmacologically malleable, providing a new strategy to treat aberrant hSSC diversity central to aging and skeletal maladies.

2024-12-01·Alzheimer's & Dementia

Regional microglial activation differs across the cortex of patients in the Alzheimer’s disease trajectory: A cross‐sectional study

Article

作者: Femminella, Grazia Daniela ; Brooks, David J ; Buckley, Christopher ; Jogaudaite, Simona ; Trigg, William ; Pasqualetti, Giuseppe ; Hinz, Rainer ; Edison, Paul ; Crook, Harry ; Gentleman, Steve ; Abarrategui, Javier Alegre ; Calsolaro, Valeria ; Tuil, Marie Emilie

AbstractBackgroundMicroglial reactivity and neuroinflammation are crucial pathological processes in Alzheimer’s Disease (AD). Several attempts to develop a treatment by supressing the immune response in AD have been made, yet these yielded very limited results. Recent studies suggest contrasting effects of microglial reactivity, indicating a biphasic response with both beneficial and deleterious effects at distinct stages of AD.We evaluated the regional differential influence of microglial reactivity on neuropathological processes across AD trajectory.Method48 patients were divided by diagnosis into control (11), Mild Cognitive Impairment (MCI, 14), and AD (23) groups. They underwent TSPO‐PET imaging, magnetic resonance imaging (MRI), and neuropsychological testing. The spectral analysis generated a TSPO‐PET impulse response function at 90 minutes (IRF90), reflecting its volume of distribution. Region of interest and voxel‐level analyses were performed, and grey matter (GM) volume was calculated using FreeSurfer and voxel‐based morphometric analysis. Additionally, post mortem brain tissue from 27 patients at Braak Stages IV‐VI was stained for CD32a and CD163, markers of pro and anti‐inflammatory activation respectively.ResultThe AD group showed increased microglial reactivity in the temporal, parietal, occipital, and medio‐temporal lobes, and the cingulate cortex compared to controls. Voxel‐wide analyses of AD and MCI patients yielded similar results across the cortex.The voxel‐wise analysis revealed both positive and negative clusters of association between tracer uptake and GM volume, with negative associations more often found in regions affected earlier in AD trajectory. This dual effect is further denoted by the presence of both CD32a‐positive and CD164‐positive microglia within the same regions in post mortem tissue.ConclusionThe contrasting effects of reactive microglia on different pathological processes show regional disparities, with deleterious effects more closely associated with regions affected in the early stages of AD. This suggests a diverging response driven by both anti‐ and pro‐inflammatory reactivity profiles. The former, neuroprotective, would emerge locally alongside early pathology, while the later, neurotoxic, would only appear with more advanced pathology.Consequently, potential treatments should promote anti‐inflammatory polarization and supress pro‐inflammatory activation in microglia for an effective therapeutic strategy.

项与 CD164 相关的新闻（医药）

2022-10-02

·中国生物技术网

Nature：利用昆虫细胞全基因组CRISPR/Cas9筛选技术揭示杀虫毒素受体

2022年9月28日，发表在《Nature》上的一项最新研究中，来自哈佛医学院董民教授等人领导的研究团队在昆虫细胞上首次利用CRISPR/Cas9筛选技术，找到了一种特异性针对昆虫的细菌蛋白毒素（Tc toxin）的受体。这一工作在分子水平上揭示了毒素的作用机理和对不同昆虫的特异性，不仅建立了对这类毒素在自然界的功能的深刻理解，而且有助于将来进一步发展高效特异的生物杀虫剂，用来控制农业害虫和其他传播疾病的昆虫。细菌蛋白毒素是很多致病菌的主要武器，例如白喉毒素，炭疽毒素，肉毒杆菌毒素等等。近年来，全基因组CRISPR/Cas9筛选技术在哺乳动物细胞上得到广泛应用，成为研究这些针对人和动物的毒素和病原菌的主要实验方法。昆虫是地球上种类最繁多的动物，在整个生态链上起到至关重要的作用。在自然界中，存在许多专门靶向昆虫的细菌蛋白毒素，有些已经被广泛地应用于农业害虫防治。现有的CRISPR/Cas9筛选技术依赖针对哺乳动物细胞的慢病毒转染系统，不适用在昆虫细胞上，大大限制了人们对针对昆虫的蛋白毒素作用机制，抗性，宿主特异性以及开发新型杀虫毒素等问题的研究。这项工作建立了在昆虫细胞上开展非病毒的全基因组CRISPR/Cas9筛选毒素受体的方法，为应用全基因组筛选这一关键技术来研究多种多样的针对昆虫的毒素，病原菌，病毒，众多虫媒病原菌和病毒，以及昆虫细胞生物学问题提供了开创性的榜样。作者主要研究的是一种来源于昆虫病原线虫肠道共生菌的细菌毒素Tc toxin。这种毒素有着非同寻常的生态角色：这类细菌寄生在土壤中的特定线虫体内，这些线虫专门寻找并入侵到土壤中的昆虫幼虫体内，然后释放出这些细菌到昆虫体腔内，这些细菌再用分泌的毒素来抑制昆虫的免疫反应，然后细菌大量繁殖，线虫再以细菌为食物，繁殖下一代，最终杀死昆虫。1998年 R H ffrench-Constant组首次报道从昆虫病原线虫共生菌，发光光杆状菌 (Photorhabdus luminescens) 中分离到活性蛋白毒素（Tc Toxin）。为了更好的利用开发昆虫病原线虫这一重要的生物防治资源，人们一直对Tc 毒素相关的分子机制的研究很感兴趣，并陆续在不同菌属细菌里发现了上千个Tc毒素家族成员，但却对其昆虫宿主因子知之甚少。董民实验室发现Tc toxin 家族的代表毒素（pTc）对多种人源细胞系毒性较低，而对果蝇S2R+细胞毒性较高，5 pM的毒素可以让50%的果蝇细胞呈现毒理表型，这暗示了果蝇S2R+细胞表面很可能存在对 Tc 毒素高特异的受体。与此同时，哈佛医学院Norbert Perrimon教授实验室于2018年开发了应用于果蝇S2R+细胞全基因CRISPR/Cas9 筛选的文库，利用整合酶介导的gRNA基因组定点整合的方法，不需要使用慢病毒转染。作者发现pTc 毒素可以通过修饰细胞内肌动蛋白抑制S2R+细胞分裂，但中毒S2R+细胞基因组依然可以保持复制，进而导致中毒S2R+细胞体积随着时间不断增大。正是利用这一特征，在实际筛选中，作者巧妙地利用30微米孔径的细胞筛分离中毒细胞以及对毒素有耐性的细胞。通过几轮的富集和高通量测序，最终鉴别出了一个单次跨膜的Mucin家族蛋白，Visgun，作为pTc毒素特异性受体。图1：Tc毒素全基因组筛选接着研究者进一步揭示了双翅目的埃及伊蚊，疟蚊以及鞘翅目的赤拟谷盗Visgun同源蛋白均可高效识别pTc毒素，而来源于鳞翅目的草地贪夜蛾和大腊螟Visgun同源蛋白则不能作为受体. 通过比对它们的蛋白序列，提示具有高度富集O-glycan修饰位点是不同昆虫物种Visgun同源蛋白能否作为pTc毒素受体的必要条件，有意思的是，人的同源蛋白CD164正好缺乏这一特征，这些发现在分子水平上解释了Tc毒素对宿主的选择特异性。最后作者以果蝇作为昆虫宿主模型，发现Visgun蛋白主要在血细胞表达，而这些细胞正是昆虫的主要免疫系统。敲除Visgun蛋白可以降低原代血细胞对pTc 毒素的敏感性，并且在被pTc毒素预处理后，这些血细胞依然保持吞噬细菌的能力。在被感染发光光杆状菌后, Visgun蛋白敲除的果蝇也表现出较低的致死率和病原菌载量，这揭示出在病原菌感染的初期，低剂量的Tc毒素被分泌到昆虫体腔后，可以通过高特异性的Visgun受体进入昆虫血细胞，通过破坏昆虫免疫系统防线，为病原细菌的进一步整殖和最终杀死宿主创造条件。图2：敲除Visgun蛋白降低果蝇血细胞对Tc毒素的敏感度论文链接：https://doi.org/10.1038/s41586-022-05250-7