Pabpc1a调控斑马鱼血管发生的机制研究

doi:10.16288/j.yczz.26-042

遗传 ›› 2026, Vol. 48 ›› Issue (7): 714-725.doi: 10.16288/j.yczz.26-042

Pabpc1a调控斑马鱼血管发生的机制研究

胡雨琴¹(), 刘帆¹, 李颖¹, 王璐¹^,²()

¹ 中国医学科学院血液病医院(中国医学科学院血液学研究所)北京协和医学院，血液与健康全国重点实验室，国家血液系统疾病临床医学研究中心，细胞生态海河实验室，天津 300020
² 天津医学健康研究院，天津 301600

收稿日期:2026-02-28 修回日期:2026-04-09 出版日期:2026-07-20 发布日期:2026-05-15
通讯作者: 王璐，博士，研究员，研究方向：发育生物学，干细胞与再生医学。E-mail: wanglu1@ihcams.ac.cn
作者简介:胡雨琴，硕士研究生，专业方向：干细胞与再生医学。E-mail: huyuqin@ihcams.ac.cn
基金资助:
国家自然科学基金项目(32400688);中国医学科学院医学与健康科技创新工程项目(2025-I2M-TS-08)

Regulatory mechanism of Pabpc1a during zebrafish vasculogenesis

Yuqin Hu¹(), Fan Liu¹, Ying Li¹, Lu Wang¹^,²()

¹ State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
² Tianjin Institutes of Health Science, Tianjin 301600, China

Received:2026-02-28 Revised:2026-04-09 Published:2026-07-20 Online:2026-05-15
Supported by:
National Natural Science Foundation of China(32400688);Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine(2025-I2M-TS-08)

摘要/Abstract

摘要：

血管发育始于胚胎早期的血管发生，该过程受到多层面、高度整合的分子网络调控，其中转录后调控机制仍有待系统解析。细胞质多聚腺苷酸结合蛋白1a (cytoplasmic poly(A) binding protein 1a，Pabpc1a)是一种关键的RNA结合蛋白，通过转录后调控参与多种生理与病理过程，但其在血管发育中的功能仍不清楚。本研究首先发现pabpc1a在血管发生的关键时间窗口于内皮细胞中表达，随后利用CRISPR/Cas9技术构建了pabpc1a基因缺失模型。功能实验表明，pabpc1a基因缺失导致动静脉特化相关基因表达失调，动静脉血管直径比例异常；而过表达pabpc1a可以有效挽救血管发生缺陷。机制上，组学分析显示pabpc1a基因缺失引起内皮细胞中广泛的基因表达紊乱，其中翻译、核糖体生物合成及能量代谢相关通路显著下调。这些结果提示，Pabpc1a可能通过协调蛋白质合成与代谢稳态来确保血管发生的正常进行。综上所述，本研究证明Pabpc1a是血管发生过程中一个不可或缺的转录后调节因子，为理解血管发育的调控网络提供了新视角。

关键词: pabpc1a, 斑马鱼, 血管发生, 动静脉特化

Abstract:

Vascular development begins with vasculogenesis during early embryogenesis. This process is controlled by a highly integrated, multi-layered molecular network. However, the role of post-transcriptional regulation in this context remains poorly understood. Cytoplasmic poly(A) binding protein 1a (Pabpc1a) is a key RNA-binding protein that regulates gene expression at the post-transcriptional level and participates in many physiological and pathological processes. Its role in vascular development, however, is still unclear. In this study, we first found that pabpc1a is highly expressed in endothelial cells during the critical window of vasculogenesis. We then generated a pabpc1a knockout model using CRISPR/Cas9. Functional analyses showed that loss of pabpc1a disrupted the expression of genes involved in arterial-venous specification and altered the arterial-to-venous diameter ratio. In contrast, overexpression of pabpc1a effectively rescued the vascular defects. Mechanistically, transcriptomic analysis revealed widespread gene expression changes in endothelial cells lacking pabpc1a. Pathways related to translation, ribosome biogenesis, and energy metabolism were significantly downregulated. These findings suggest that Pabpc1a regulates vasculogenesis by coordinating protein synthesis and metabolic homeostasis. In summary, our study demonstrates Pabpc1a as an essential post-transcriptional regulator during vasculogenesis and provides new insight into the regulatory network governing vascular development.

Key words: pabpc1a, zebrafish, vasculogenesis, arterial-venous specification

胡雨琴, 刘帆, 李颖, 王璐. Pabpc1a调控斑马鱼血管发生的机制研究[J]. 遗传, 2026, 48(7): 714-725.

Yuqin Hu, Fan Liu, Ying Li, Lu Wang. Regulatory mechanism of Pabpc1a during zebrafish vasculogenesis[J]. Hereditas(Beijing), 2026, 48(7): 714-725.

图/表 9

附表1

附图1

附图2

图1

图2

图3

图4

附图3

图5

参考文献 32

[1]	Eberlein J, Herdt L, Malchow J, Rittershaus A, Baumeister S, Helker CS. Molecular and cellular mechanisms of vascular development in zebrafish. Life (Basel), 2021, 11(10): 1088. pmid: 34685459
[2]	Wolf K, Hu HD, Isaji T, Dardik A. Molecular identity of arteries, veins, and lymphatics. J Vasc Surg, 2019, 69(1): 253-262. pmid: 30154011
[3]	Ellertsdóttir E, Lenard A, Blum Y, Krudewig A, Herwig L, Affolter M, Belting HG. Vascular morphogenesis in the zebrafish embryo. Dev Biol, 2010, 341(1): 56-65. pmid: 19895803
[4]	Greenspan LJ, Weinstein BM. To be or not to be: endothelial cell plasticity in development, repair, and disease. Angiogenesis, 2021, 24(2): 251-269. pmid: 33449300
[5]	Bai W, Yin DP, Chen G, Lu Y, Jiang Q, Li KR, Yao J, Cao C. Endothelial RAB5IF is required for pathological and developmental retinal angiogenesis. Nat Commun, 2025, 16(1): 11402. pmid: 41390488
[6]	Zhao P, Li D, Liu XW. DcR3, stabilized by the RNA-binding protein IGF2BP2, promotes proliferation, invasion, and migration of trophoblast cells and facilitates angiogenesis. BMC Pregnancy Childbirth, 2025, 26(1): 2. pmid: 41299320
[7]	Han HX, Lin T, Wang ZY, Song JJ, Fang ZY, Zhang J, You XM, Du YP, Ye J, Zhou GX. RNA-binding motif 4 promotes angiogenesis in HCC by selectively activating VEGF-A expression. Pharmacol Res, 2023, 187: 106593. pmid: 36496136
[8]	Biziaev N, Shuvalov A, Salman A, Egorova T, Shuvalova E, Alkalaeva E. The impact of mRNA poly(A) tail length on eukaryotic translation stages. Nucleic Acids Res, 2024, 52(13): 7792-7808. pmid: 38874498
[9]	Kajjo S, Sharma S, Chen S, Brothers WR, Cott M, Hasaj B, Jovanovic P, Larsson O, Fabian MR. PABP prevents the untimely decay of select mRNA populations in human cells. EMBO J, 2022, 41(6): e108650. pmid: 35156721
[10]	Cao SM, Wu H, Yuan GH, Pan YH, Zhang J, Liu YX, Li SQ, Xu YF, Wei MY, Yang L, Chen LL. Altered nucleocytoplasmic export of adenosine-rich circRNAs by PABPC 1 contributes to neuronal function. Mol Cell, 2024, 84(12): 2304-2319.e8. pmid: 38838666
[11]	Boeynaems S, Dorone Y, Zhuang YR, Shabardina V, Huang GZ, Marian A, Kim G, Sanyal A, Şen NE, Griffith D, Docampo R, Lasker K, Ruiz-Trillo I, Auburger G, Holehouse AS, Kabashi E, Lin Y, Gitler AD. Poly(A)-binding protein is an ataxin-2 chaperone that regulates biomolecular condensates. Mol Cell, 2023, 83(12): 2020-2034.e6. pmid: 37295429
[12]	Wang JL, Zhang X, Greene GH, Xu GY, Dong XN. PABP/purine-rich motif as an initiation module for cap-independent translation in pattern-triggered immunity. Cell, 2022, 185(17): 3186-3200.e17. pmid: 35907403
[13]	Sun CG, Xu X, Chen ZY, Zhou FQ, Wang W, Chen JZ, Sun MY, Wang F, Jiang LJ, Ji M, Liu SQ, Xu JY, He MM, Su BW, Liu XL, Gao YD, Wei H, Li J, Wang XS, Zhao M, Yu J, Ma YN. Selective translational control by PABPC1 phase separation regulates blast crisis and therapy resistance in chronic myeloid leukaemia. Nat Cell Biol, 2025, 27(4): 683-695. pmid: 40102686
[14]	Chen ZH, Zeng CW, Yang L, Che Y, Chen ML, Sau L, Wang BT, Zhou KR, Chen Y, Qing Y, Shen C, Zhang TJ, Wunderlich M, Wu D, Li W, Wang K, Leung K, Sun M, Tang TT, He X, Zhang LJ, Swaminathan S, Mulloy JC, Muschen M, Huang HL, Weng HY, Xiao G, Deng XL, Chen JJ. YTHDF2 promotes ATP synthesis and immune evasion in B cell malignancies. Cell, 2025, 188(2): 331-351.e30. pmid: 39694037
[15]	Lawson ND, Weinstein BM. In vivo imaging of embryonic vascular development using transgenic zebrafish. Dev Biol, 2002, 248(2): 307-318. pmid: 12167406
[16]	Bertrand JY, Chi NC, Santoso B, Teng ST, Stainier DYR, Traver D. Haematopoietic stem cells derive directly from aortic endothelium during development. Nature, 2010, 464(7285): 108-111. pmid: 20154733
[17]	Zhang CX, Liu F. A brief protocol for high-resolution whole mount in situ hybridization in zebrafish. Hereditas(Beijing), 2013, 35(4): 522-528.
	张春霞, 刘峰. 斑马鱼高分辨率整胚原位杂交实验方法与流程. 遗传, 2013, 35(4): 522-528.
[18]	Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF. Stages of embryonic development of the zebrafish. Dev Dyn, 1995, 203(3): 253-310. pmid: 8589427
[19]	Mishima Y, Fukao A, Kishimoto T, Sakamoto H, Fujiwara T, Inoue K. Translational inhibition by deadenylation- independent mechanisms is central to microRNA- mediated silencing in zebrafish. Proc Natl Acad Sci USA, 2012, 109(4): 1104-1109. pmid: 22232654
[20]	Li Y, Li C, Liu MY, Liu SC, Liu F, Wang L. The RNA-binding protein CSDE1 promotes hematopoietic stem and progenitor cell generation via translational control of Wnt signaling. Development, 2023, 150(21): dev201890. pmid: 37874038
[21]	Mitchell CD, Morris CA, Wild M, Cunningham A, Chuesiang P, Mohammed AA, Nagalo BM, Rusch NJ, Fouda AY, Shosha E. HDAC3 mediates retinal endothelial cell metabolic reprogramming and angiogenesis. Acta Pharmacol Sin, 2026, 47(4): 1058-1069. pmid: 41023273
[22]	Dong XX, Zhang QQ, Yu XY, Wang D, Ma JM, Ma J, Shi SH. Metabolic lactate production coordinates vasculature development and progenitor behavior in the developing mouse neocortex. Nat Neurosci, 2022, 25(7): 865-875. pmid: 35726058
[23]	Jin DQ, Zhu DQ, Fang YB, Chen YW, Yu GH, Pan WJ, Liu D, Li F, Zhong TP. Vegfa signaling regulates diverse artery/vein formation in vertebrate vasculatures. J Genet Genomics, 2017, 44(10): 483-492. pmid: 29037991
[24]	Lawson ND, Scheer N, Pham VN, Kim CH, Chitnis AB, Campos-Ortega JA, Weinstein BM. Notch signaling is required for arterial-venous differentiation during embryonic vascular development. Development, 2001, 128(19): 3675-3683. pmid: 11585794
[25]	Moser M, Patterson C. Bone morphogenetic proteins and vascular differentiation: BMPing up vasculogenesis. Thromb Haemost, 2005, 94(4): 713-718. pmid: 16270622
[26]	Zhou R, Hu L, Li R, Chen H, Zhang XL, Hua L, Che LQ, Lin Y, Xu SY, Feng B, Jin C, Wu D, Zhuo Y, Fang ZF. Methionine adenosyl-transferase 2A promotes placental angiogenesis by regulating VEGF-A translation via the mTORC1 signalling pathway. J Physiol, 2026, 604(5): 2191-2211. pmid: 41579147
[27]	Shen XY, Wen ZZ, Deng SZ, Qiu YX, Ma WJ, Dong XY, Gong J, Zhang Y, Liu D, Xu B. Regulation of hindbrain vascular development by rps20 in zebrafish. Cells, 2025, 14(14): 1070. pmid: 40710323
[28]	De Bruin RG, Van Der Veer EP, Prins J, Lee DH, Dane MJC, Zhang HY, Roeten MK, Bijkerk R, De Boer HC, Rabelink TJ, Van Zonneveld AJ, Van Gils JM. The RNA-binding protein quaking maintains endothelial barrier function and affects VE-cadherin and β-catenin protein expression. Sci Rep, 2016, 6: 21643. pmid: 26905650
[29]	Kurosu T, Ohga N, Hida Y, Maishi N, Akiyama K, Kakuguchi W, Kuroshima T, Kondo M, Akino T, Totsuka Y, Shindoh M, Higashino F, Hida K. HuR keeps an angiogenic switch on by stabilising mRNA of VEGF and COX-2 in tumour endothelium. Br J Cancer, 2011, 104(5): 819-829. pmid: 21285980
[30]	Galbán S, Kuwano Y, Pullmann R, Martindale JL, Kim HH, Lal A, Abdelmohsen K, Yang XL, Dang YJ, Liu JO, Lewis SM, Holcik M, Gorospe M. RNA-binding proteins HuR and PTB promote the translation of hypoxia- inducible factor 1alpha. Mol Cell Biol, 2008, 28(1): 93-107. pmid: 17967866
[31]	Swift MR, Weinstein BM. Arterial-venous specification during development. Circ Res, 2009, 104(5): 576-588. pmid: 19286613
[32]	Modic M, Kuret K, Steinhauser S, Faraway R, Van Genderen E, De Los Mozos IR, Novljan J, Vičič Ž, Lee FCY, Ten Berge D, Luscombe NM, Ule J. Poised PABP- RNA hubs implement signal-dependent mRNA decay in development. Nat Struct Mol Biol, 2024, 31(9): 1439-1447. pmid: 39054355

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

基因名称	引物序列(5′→3′)	用途
pabpc1a	F：GTTTTCACCATTCGGCACCA R：GATCTGACCTTGTGTTAGACGG	探针合成
hey2	F：CTGCCAAGTTGGAGAAAGCG R：GTTTCCAACACAGTGCGACG	探针合成
pabpc1a	F：TCTATCCGGGTGTGCAGAGA R：TGTTACCCACACCGCTCTTC	qRT-PCR
dltC	F：ATTATTGCACCGAACCCA R：AAAATAGACCGCCCCAAC
flt4	F：TCCCTTCTTCTCAGGTCTGGT R：CTGACCCTGGCGATCAGTAA
hey2	F：ATTGATGTGGGCAGCGAGAA R：TGGGATGTGGTGGATGTGGA
pabpc1a	F：TATTATCTCGAGATGAACCCCAGCGCGCCCAGT R：TATTATTCTAGATTAGACGGCGGGCACAGCAG	mRNA合成
pabpc1a	Pabpc1a-hifi-F：TGATGACAAGATGAACCCCAGCGCGCCC Pabpc1a-hifi-R：AAGCTGGGTCGACGGCGGGCACAGCAGG Vector-hifi-F：GCCCGCCGTCGACCCAGCTTTCTTGTAC Vector-hifi-R：TGGGGTTCATCTTGTCATCATCGTCCTTG	质粒构建
pabpc1a	F：GAAGAGCGGTGTGGGTAAC R：AACCCTGATGTAAGGCGGTG	基因型鉴定

Pabpc1a调控斑马鱼血管发生的机制研究

Regulatory mechanism of Pabpc1a during zebrafish vasculogenesis

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 9

参考文献 32

相关文章 15

编辑推荐

Metrics

[1]	欧阳沛东, 唐嘉兰, 吴成超, 李晓玉, 柯珊珊, 张晶晶. 基于斑马鱼模型探究synpo在颅内出血中的作用机制[J]. 遗传, 2026, 48(4): 407-420.
[2]	李雨洁, 李飞飞, 张文清, 陈琪. tcirg1b基因缺失导致斑马鱼中枢神经稳态失衡的机制[J]. 遗传, 2026, 48(2): 201-212.
[3]	郑少辉, 刘洋, 夏新欣, 刘彦梅. 碱基编辑技术及其在斑马鱼中的开发应用[J]. 遗传, 2026, 48(1): 46-60.
[4]	高云海, 邓家杰, 肖霄, 潘鲁湲, 何牡丹, 张蕴斌. 斑马鱼ppp6r3调控性腺分化和配子发生的作用研究[J]. 遗传, 2025, 47(9): 1023-1031.
[5]	林杰豪, 杨童舒, 张文清, 刘伟. Lyl1不同转录本在斑马鱼原始造血中的作用[J]. 遗传, 2025, 47(5): 573-588.
[6]	寇涵婧, 黄志斌, 张文清, 陈琪. V-ATPase a3亚基调控小胶质细胞吞噬体成熟的机制[J]. 遗传, 2025, 47(11): 1256-1268.
[7]	刘吉祥, 赖思婷, 白晶, 徐进. Il34拯救甲硝唑导致的斑马鱼中枢神经系统轴突再生障碍[J]. 遗传, 2024, 46(6): 478-489.
[8]	洪佳馨, 徐颂恩, 张文清, 刘伟. Pu.1和cMyb在斑马鱼中性粒细胞发育中的相互作用[J]. 遗传, 2024, 46(4): 319-332.
[9]	孙飘, 李颖, 刘帆, 王璐. TPI缺乏症斑马鱼模型的构建及分析[J]. 遗传, 2024, 46(3): 232-241.
[10]	杨晓君, 黄振瀚, 刘伟, 张文清, 黄志斌. CD209同源基因在斑马鱼中的鉴定及功能表征[J]. 遗传, 2024, 46(11): 947-957.
[11]	李凯伦, 卢荆奥, 陈小辉, 张文清, 刘伟. 尿囊素促进破骨细胞缺陷斑马鱼骨折修复[J]. 遗传, 2023, 45(4): 341-353.
[12]	卢荆澳, 黄春燕, 林芷茵, 唐政, 马宁, 黄志斌. cd99l2基因调控斑马鱼白细胞组织间的迁移机制[J]. 遗传, 2022, 44(9): 798-809.
[13]	郑鹏飞, 谢海波, 朱盼盼, 赵呈天. 斑马鱼神经底板处神经元的分布及特征[J]. 遗传, 2022, 44(6): 510-520.
[14]	张婷婷, 刘峰. 斑马鱼蛋白酪氨酸硫酸化修饰的检测方法研究[J]. 遗传, 2022, 44(2): 178-186.
[15]	贾婷婷, 雷蕾, 吴歆媛, 蔡顺有, 陈艺璇, 薛钰. 二甲双胍对斑马鱼骨骼发育及损伤修复的机制研究[J]. 遗传, 2022, 44(1): 68-79.