生物技术进展 ›› 2024, Vol. 14 ›› Issue (5): 793-804.DOI: 10.19586/j.2095-2341.2024.0078
• 进展评述 • 上一篇
万令飞(), 潘文婷, 雍雨婷, 李元帅, 赵悦, 阎新龙(
)
收稿日期:
2024-04-11
接受日期:
2024-07-02
出版日期:
2024-09-25
发布日期:
2024-10-22
通讯作者:
阎新龙
作者简介:
万令飞 E-mail: wan-lingfei@outlook.com;
基金资助:
Lingfei WAN(), Wenting PAN, Yuting YONG, Yuanshuai LI, Yue ZHAO, Xinlong YAN(
)
Received:
2024-04-11
Accepted:
2024-07-02
Online:
2024-09-25
Published:
2024-10-22
Contact:
Xinlong YAN
摘要:
肝纤维化是一种严重威胁人类健康的疾病,单细胞转录组测序技术为揭示其复杂的病理机制提供了全新途径。传统的研究方法在识别肝纤维化中不同细胞亚群及其基因表达变化方面存在局限,难以深入理解疾病机制。概述了单细胞转录组测序技术在肝纤维化过程中对不同细胞亚群类型的研究进展,单细胞RNA测序技术能够精确地解析不同细胞类型的基因表达及异质性,揭示肝纤维化过程中细胞亚群的动态变化及相关基因的表达,进而有助于理解各类细胞亚型在肝纤维化中的功能、相互作用及其对疾病进展的贡献。进一步探讨了该技术在肝纤维化研究中的重要意义与应用前景,通过这一技术,可以鉴定出与纤维化相关的关键基因和信号通路,为早期诊断、治疗靶点的发现以及新疗法的制定提供理论依据。此外,结合空间转录组测序技术,研究者可以在空间维度上观察细胞在组织中的分布,进一步提升对肝纤维化微环境的理解。该技术有助于深入理解肝纤维化的病理机制,为寻找新的治疗靶点和制定早期诊断及治疗策略提供了创新思路。
中图分类号:
万令飞, 潘文婷, 雍雨婷, 李元帅, 赵悦, 阎新龙. 单细胞转录组测序技术在肝纤维化中的研究进展[J]. 生物技术进展, 2024, 14(5): 793-804.
Lingfei WAN, Wenting PAN, Yuting YONG, Yuanshuai LI, Yue ZHAO, Xinlong YAN. Research Progress of Single-cell Transcriptome Sequencing Technology in Liver Fibrosis[J]. Current Biotechnology, 2024, 14(5): 793-804.
1 | HAMMEL P, COUVELARD A, O'TOOLE D, et al.. Regression of liver fibrosis after biliary drainage in patients with chronic pancreatitis and stenosis of the common bile duct[J]. N. Engl. J. Med., 2001, 344(6): 418-423. |
2 | KWEON Y O, GOODMAN Z D, DIENSTAG J L, et al.. Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis B[J]. J. Hepatol., 2001, 35(6): 749-755. |
3 | ARTHUR M J P. Reversibility of liver fibrosis and cirrhosis following treatment for hepatitis C[J]. Gastroenterology, 2002, 122(5): 1525-1528. |
4 | CZAJA A J, CARPENTER H A. Decreased fibrosis during corticosteroid therapy of autoimmune hepatitis[J]. J. Hepatol., 2004, 40(4): 646-652. |
5 | DIXON J B, BHATHAL P S, HUGHES N R, et al.. Nonalcoholic fatty liver disease: improvement in liver histological analysis with weight loss[J]. Hepatology, 2004, 39(6): 1647-1654. |
6 | BURT A D. Liver fibrosis[J]. Br. Med. J., 1992, 305(6853):537-538. |
7 | HERNANDEZ-GEA V, FRIEDMAN S L. Pathogenesis of liver fibrosis[J]. Ann. Rev. Pathol. Mechan. Disease, 2011, 6(1):425-456. |
8 | ROCKEY D C, BELL P D, HILL J A. Fibrosis: a common pathway to organ injury and failure[J]. N. Engl. J. Med., 2015, 372(12): 1138-1149. |
9 | WANG S, FRIEDMAN S L. Hepatic fibrosis: a convergent response to liver injury that is reversible[J]. J. Hepatol., 2020, 73(1): 210-211. |
10 | DREW L. Tipping the balance[J/OL]. Nature, 2018, 564(7736): S74-S75[2024-05-13]. . |
11 | 杨瑞华,李芹,陈玮.扶正化瘀胶囊治疗慢性乙型肝炎肝纤维化疗效的Meta分析[J].中华肝脏病杂志,2015,23(4):295-296. |
YANG R H, LI Q, CHEN W. Efficacy and safety of Fuzhenghuayu capsule for treating liver fibrosis in patients with chronic hepatitis B: a meta-analysis[J]. Chin. J. Hepatol., 2015, 23(4): 295-296. | |
12 | 苗亮,杨婉娜,董晓琴,等.安络化纤丸联合恩替卡韦治疗可显著提高慢性乙型肝炎病毒感染者肝纤维化的改善率[J].中华肝脏病杂志,2019,27(7):521-526. |
MIAO L, YANG W N, DONG X Q, et al.. Combined anluohuaxianwan and entecavir treatment significantly improve the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection[J]. Chin. J. Hepatol., 2019, 27(7): 521-526. | |
13 | JI D, CHEN Y, BI J, et al.. Entecavir plus Biejia-Ruangan compound reduces the risk of hepatocellular carcinoma in Chinese patients with chronic hepatitis B[J]. J. Hepatol., 2022, 77(6): 1515-1524. |
14 | LIU Y Q, ZHANG C, LI J W, et al.. An-Luo-Hua-Xian pill improves the regression of liver fibrosis in chronic hepatitis B patients treated with entecavir[J]. J. Clin. Transl. Hepatol., 2023, 11(2): 304-313. |
15 | NEUSCHWANDER-TETRI B A. Targeting the FXR nuclear receptor to treat liver disease[J]. Gastroenterology, 2015, 148(4): 704-706. |
16 | HARRISON S A, RINELLA M E, ABDELMALEK M F, et al.. NGM282 for treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial[J]. Lancet, 2018, 391(10126): 1174-1185. |
17 | QIAN T, FUJIWARA N, KONERU B, et al.. Molecular signature predictive of long-term liver fibrosis progression to inform antifibrotic drug development[J]. Gastroenterology, 2022, 162(4): 1210-1225. |
18 | TANG F, BARBACIORU C, WANG Y, et al.. mRNA-Seq whole-transcriptome analysis of a single cell[J]. Nat. Methods, 2009, 6(5): 377-382. |
19 | GAWAD C, KOH W, QUAKE S R. Single-cell genome sequencing: current state of the science[J]. Nat. Rev. Genet., 2016, 17(3): 175-188. |
20 | TANAY A, REGEV A. Scaling single-cell genomics from phenomenology to mechanism[J]. Nature, 2017, 541(7637): 331-338. |
21 | BASLAN T, HICKS J. Unravelling biology and shifting paradigms in cancer with single-cell sequencing[J]. Nat. Rev. Cancer, 2017, 17(9): 557-569. |
22 | VAN DE SANDE B, LEE J S, MUTASA-GOTTGENS E, et al.. Applications of single-cell RNA sequencing in drug discovery and development[J]. Nat. Rev. Drug Discov., 2023, 22(6): 496-520. |
23 | QUAIL M A, KOZAREWA I, SMITH F, et al.. A large genome center's improvements to the Illumina sequencing system[J]. Nat. Methods, 2008, 5(12): 1005-1010. |
24 | HAO Y, STUART T, KOWALSKI M H, et al.. Dictionary learning for integrative, multimodal and scalable single-cell analysis[J]. Nat. Biotechnol., 2024, 42(2): 293-304. |
25 | WOLF F A, ANGERER P, THEIS F J. SCANPY large-scale single-cell gene expression data analysis[J/OL]. Genome Biol., 2018, 19(1): 15[2024-05-13]. . |
26 | ZHENG G X, TERRY J M, BELGRADER P, et al.. Massively parallel digital transcriptional profiling of single cells[J/OL]. Nat. Commun., 2017, 8: 14049[2024-05-13]. . |
27 | TRAPNELL C, CACCHIARELLI D, GRIMSBY J, et al.. The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells[J]. Nat. Biotechnol., 2014, 32(4): 381-386. |
28 | FRIEDMAN S L. Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver[J]. Physiol. Rev., 2008, 88(1): 125-172. |
29 | SHERMAN M H. Stellate cells in tissue repair, inflammation, and cancer[J]. Annu. Rev. Cell Dev. Biol., 2018, 34: 333-355. |
30 | TSUCHIDA T, FRIEDMAN S L. Mechanisms of hepatic stellate cell activation[J]. Nat. Rev. Gastroenterol. Hepatol., 2017, 14(7): 397-411. |
31 | BAGHAEI K, MAZHARI S, TOKHANBIGLI S, et al.. Therapeutic potential of targeting regulatory mechanisms of hepatic stellate cell activation in liver fibrosis[J]. Drug Discov. Today, 2022, 27(4): 1044-1061. |
32 | WANG S S, TANG X T, LIN M, et al.. Perivenous stellate cells are the main source of myofibroblasts and cancer-associated fibroblasts formed after chronic liver injuries[J]. Hepatology, 2021, 74(3): 1578-1594. |
33 | KRENKEL O, HUNDERTMARK J, RITZ T P, et al.. Single cell RNA sequencing identifies subsets of hepatic stellate cells and myofibroblasts in liver fibrosis[J/OL]. Cells, 2019, 8(5): 503[2024-05-13]. . |
34 | TSUCHIYA Y, SEKI T, KOBAYASHI K, et al.. Fibroblast growth factor 18 stimulates the proliferation of hepatic stellate cells, thereby inducing liver fibrosis[J/OL]. Nat. Commun., 2023, 14(1): 6304[2024-05-13]. . |
35 | ROSENTHAL S B, LIU X, GANGULY S, et al.. Heterogeneity of HSCs in a mouse model of NASH[J]. Hepatology, 2021, 74(2): 667-685. |
36 | LEI L, BRUNEAU A, MOURABIT H E L, et al.. Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis[J]. Hepatology, 2022, 76(5): 1360-1375. |
37 | IWANO M, PLIETH D, DANOFF T M, et al.. Evidence that fibroblasts derive from epithelium during tissue fibrosis[J]. J. Clin. Invest., 2002, 110(3): 341-350. |
38 | OMENETTI A, PORRELLO A, JUNG Y, et al.. Hedgehog signaling regulates epithelial-mesenchymal transition during biliary fibrosis in rodents and humans[J]. J. Clin. Invest., 2008, 118(10): 3331-3342. |
39 | TAURA K, MIURA K, IWAISAKO K, et al.. Hepatocytes do not undergo epithelial-mesenchymal transition in liver fibrosis in mice[J]. Hepatology, 2010, 51(3): 1027-1036. |
40 | CHU A S, DIAZ R, HUI J J, et al.. Lineage tracing demonstrates no evidence of cholangiocyte epithelial-to-mesenchymal transition in murine models of hepatic fibrosis[J]. Hepatology, 2011, 53(5): 1685-1695. |
41 | ZHU C, KIM K, WANG X, et al.. Hepatocyte Notch activation induces liver fibrosis in nonalcoholic steatohepatitis[J/OL]. Sci. Transl. Med., 2018, 10(468): eaat0344[2024-05-13]. . |
42 | WANG G, DUAN J, PU G, et al.. The Annexin A2-Notch regulatory loop in hepatocytes promotes liver fibrosis in NAFLD by increasing osteopontin expression[J/OL]. Biochim. Biophys. Acta Mol. Basis Dis., 2022, 1868(8): 166413[2024-05-13]. . |
43 | SCHULIEN I, HOCKENJOS B, SCHMITT-GRAEFF A, et al.. The transcription factor c-Jun/AP-1 promotes liver fibrosis during non-alcoholic steatohepatitis by regulating Osteopontin expression[J]. Cell Death Differ., 2019, 26(9): 1688-1699. |
44 | RAMACHANDRAN P, DOBIE R, WILSON-KANAMORI J R, et al.. Resolving the fibrotic niche of human liver cirrhosis at single-cell level[J]. Nature, 2019, 575(7783): 512-518. |
45 | ZHANG S, WAN D, ZHU M, et al.. CD11b+CD43hi Ly6Clo splenocyte-derived macrophages exacerbate liver fibrosis via spleen-liver axis[J]. Hepatology, 2023, 77(5): 1612-1629. |
46 | MENG X M, WANG S, HUANG X R, et al.. Inflammatory macrophages can transdifferentiate into myofibroblasts during renal fibrosis[J/OL]. Cell Death Dis., 2016, 7(12): e2495[2024-05-12]. . |
47 | WANG Y Y, JIANG H, PAN J, et al.. Macrophage-to-myofibroblast transition contributes to interstitial fibrosis in chronic renal allograft injury[J]. J. Am. Soc. Nephrol., 2017, 28(7): 2053-2067. |
48 | LITTLE K, LLORIÁN-SALVADOR M, TANG M, et al.. Macrophage to myofibroblast transition contributes to subretinal fibrosis secondary to neovascular age-related macular degeneration[J/OL]. J. Neuroinflam., 2020, 17(1): 355[2024-05-13]. . |
49 | ZHAO J, ZHANG S, LIU Y, et al.. Single-cell RNA sequencing reveals the heterogeneity of liver-resident immune cells in human[J/OL]. Cell Discov., 2020, 6: 22[2024-05-13]. . |
50 | ZHANG Y, LI J, LI H, et al.. Single-cell RNA sequencing to dissect the immunological network of liver fibrosis in Schistosoma japonicum-infected mice[J/OL]. Front. Immunol., 2022, 13: 980872[2024-05-13]. . |
51 | SCHLEDZEWSKI K, GÉRAUD C, ARNOLD B, et al.. Deficiency of liver sinusoidal scavenger receptors stabilin-1 and-2 in mice causes glomerulofibrotic nephropathy via impaired hepatic clearance of noxious blood factors[J]. J. Clin. Invest., 2011, 121(2): 703-714. |
52 | POISSON J, LEMOINNE S, BOULANGER C, et al.. Liver sinusoidal endothelial cells: physiology and role in liver diseases[J]. J. Hepatol., 2017, 66(1): 212-227. |
53 | SHETTY S, LALOR P F, ADAMS D H. Liver sinusoidal endothelial cells-gatekeepers of hepatic immunity[J]. Nat. Rev. Gastroenterol. Hepatol., 2018, 15(9): 555-567. |
54 | MARRONE G, SHAH V H, GRACIA-SANCHO J. Sinusoidal communication in liver fibrosis and regeneration[J]. J. Hepatol., 2016, 65(3): 608-617. |
55 | MACPARLAND S A, LIU J C, MA X Z, et al.. Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations[J/OL]. Nat. Commun., 2018, 9(1): 4383[2024-05-13]. . |
56 | HALPERN K B, SHENHAV R, MASSALHA H, et al.. Paired-cell sequencing enables spatial gene expression mapping of liver endothelial cells[J]. Nat. Biotechnol., 2018, 36(10): 962-970. |
57 | ZEISBERG E M, TARNAVSKI O, ZEISBERG M, et al.. Endothelial-to-mesenchymal transition contributes to cardiac fibrosis[J]. Nat. Med., 2007, 13(8): 952-961. |
58 | ZHANG Y, WU X, LI Y, et al.. Endothelial to mesenchymal transition contributes to arsenic-trioxide-induced cardiac fibrosis[J/OL]. Sci. Rep., 2016, 6: 33787[2024-05-13]. . |
59 | GONZALES J, HOLBERT K, CZYSZ K, et al.. Hemin-induced endothelial dysfunction and endothelial to mesenchymal transition in the pathogenesis of pulmonary hypertension due to chronic hemolysis[J/OL]. Int. J. Mol. Sci., 2022, 23(9): 4763[2024-05-13]. . |
60 | NIE X, WU Z, SHANG J, et al.. Curcumol suppresses endothelial-to-mesenchymal transition via inhibiting the AKT/GSK3β signaling pathway and alleviates pulmonary arterial hypertension in rats[J/OL]. Eur. J. Pharmacol., 2023, 943: 175546[2024-05-13]. . |
61 | SHI Z, ZHANG K, CHEN T, et al.. Transcriptional factor ATF3 promotes liver fibrosis via activating hepatic stellate cells[J/OL]. Cell Death Dis., 2020, 11(12): 1066[2024-05-13]. . |
62 | HALPERN K B, SHENHAV R, MATCOVITCH-NATAN O, et al.. Single-cell spatial reconstruction reveals global division of labour in the mammalian liver[J]. Nature, 2017, 542(7641): 352-356. |
63 | DOBIE R, WILSON-KANAMORI J R, HENDERSON B E P, et al.. Single-cell transcriptomics uncovers zonation of function in the mesenchyme during liver fibrosis[J]. Cell Rep., 2019, 29(7): 1832-1847.e8. |
64 | 王惠,赵鹏翔,张旭娟,等.间充质干细胞在疾病治疗中的应用潜力[J].生物技术进展,2021,11(6):688-693. |
WANG H, ZHAO P X, ZHANG X J, et al.. The application potential of mesenchymal stem cells in the treatment of diseases[J]. Curr. Biotechnol., 2021, 11(6): 688-693. |
[1] | 李凯, 付军, 陈锐, 陈笑芸, 李亮. 基于免扩增高通量测序的转基因定量检测方法研究[J]. 生物技术进展, 2024, 14(4): 610-617. |
[2] | 孙卓婧, 徐道青, 唐巧玲, 王维. 韩国转基因生物安全管理与发展现状[J]. 生物技术进展, 2024, 14(3): 360-367. |
[3] | 张佳聪, 鲁纪刚. 基于CRISPR/Cas9系统建立新吉富罗非鱼双等位基因敲除技术——以SLC24A5基因为例[J]. 生物技术进展, 2024, 14(3): 442-450. |
[4] | 孙佳琪, 郭嘉, 张闯, 柳青, 王梓钰, 夏涵超, 钱步轩, 赵方方, 王棋, 刘剑锋, 刘相国. 亚磷酸脱氢酶在基因工程改造微生物和植物中的研究进展[J]. 生物技术进展, 2024, 14(2): 173-181. |
[5] | 纪艺, 王凯莉, 余卉茹, 赵新, 丁霖, 彭城, 徐俊锋, 陈笑芸. 羊源性基因组DNA标准物质研制[J]. 生物技术进展, 2024, 14(1): 125-132. |
[6] | 赵晨阳, 刘晓梦, 邢亮彬, 李亚丽, 赵立新, 艾连峰, 哈婧. 基于气相色谱-质谱法测定塞来昔布中磺酸酯类基因毒性杂质的残留量[J]. 生物技术进展, 2024, 14(1): 85-93. |
[7] | 张安红, 肖娟丽, 赵战胜, 王志安, 刘圆, 罗晓丽. 转基因抗虫棉研究进展[J]. 生物技术进展, 2023, 13(5): 657-662. |
[8] | 郭柯灼, 刘莹, 温小杰, 周晓飞, 刘冰 (编译). 巴基斯坦农业生物技术年报(2021)[J]. 生物技术进展, 2022, 12(5): 793-799. |
[9] | 宋燚, 贾思雨, 武丽娜, 张伟, 欧晓娟, 黄坚. 遗传性胆红素代谢障碍与胆汁淤积NGS方法的建立及应用[J]. 生物技术进展, 2022, 12(4): 591-599. |
[10] | 王迪, 苗朝华, 金芜军. 新加坡农业生物技术年报(2020)[J]. 生物技术进展, 2021, 11(6): 813-817. |
[11] | 权春菊, 郑忠亮. CRISPR/Cas及其衍生编辑技术在基因治疗中的应用进展[J]. 生物技术进展, 2021, 11(4): 518-525. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||
版权所有 © 2021《生物技术进展》编辑部