切换至 "中华医学电子期刊资源库"

中华细胞与干细胞杂志(电子版) ›› 2026, Vol. 16 ›› Issue (03) : 185 -190. doi: 10.3877/cma.j.issn.2095-1221.2026.03.007

综述

人类多能与全能干细胞特征及体外胚胎模型研究进展
谭亚超1, 刘丽2, 高帅2,(), 邸科前1,()   
  1. 1710007 保定,河北大学基础医学院
    2100080 北京,中国农业大学动物科学技术学院
  • 收稿日期:2025-11-26 出版日期:2026-06-01
  • 通信作者: 高帅, 邸科前
  • 基金资助:
    国家重点研发计划(2024YFA1802400)

Progress in human pluripotent and totipotent stem cell characteristics and in vitro embryo models

Yachao Tan1, Li Liu2, Shuai Gao2,(), Keqian Di1,()   

  1. 1School of Basic Medical Sciences, Hebei University, Baoding 071007, China
    2College of Animal Science and Technology, China Agricultural University, Beijing 100080, China
  • Received:2025-11-26 Published:2026-06-01
  • Corresponding author: Shuai Gao, Keqian Di
引用本文:

谭亚超, 刘丽, 高帅, 邸科前. 人类多能与全能干细胞特征及体外胚胎模型研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2026, 16(03): 185-190.

Yachao Tan, Li Liu, Shuai Gao, Keqian Di. Progress in human pluripotent and totipotent stem cell characteristics and in vitro embryo models[J/OL]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2026, 16(03): 185-190.

人类多能干细胞与全能干细胞是研究早期胚胎发育的重要体外模型。不同发育潜能的干细胞在模拟胚胎发育过程、构建类胚胎模型及研究胚内外谱系分化方面展现出独特优势。本文总结近年来多能性与全能性干细胞领域的研究进展,从不同多能状态干细胞系的相继建立,到具有胚内及胚外发育潜能的全能性相关细胞模型的成功捕获,回顾体外干细胞模型从多能性向全能性回溯的研究历程。从建系方法、分子特征及发育潜能3个维度,比较不同状态干细胞的异同,并探讨基于这些模型构建的类囊胚和着床后胚胎样结构在模拟早期发育中的应用价值。

Human pluripotent and totipotent-like stem cells serve as crucial in vitro models for investigating early embryonic development. Stem cells with distinct developmental potentials exhibit unique advantages in simulating embryonic development, constructing embryo-like models, and exploring the differentiation of embryonic and extraembryonic lineages. This review summarizes recent research advances in the fields of pluripotent and totipotent stem cells, outlining progress in converting stem cell models from pluripotency toward totipotency in vitro, ranging from the successive establishment of stem cell lines with different pluripotent states to the successful capture of totipotency-related cell models possessing both embryonic and extraembryonic developmental potentials. Furthermore, it compares the similarities and differences among stem cells in various states from three dimensions: establishment methodologies, molecular characteristics, and developmental potentials, and discusses the application value of blastoids and post-implantation embryo-like structures derived from these models in simulating early developmental processes.

表1 部分人类多能与全能干细胞类型及核心特征
细胞类型 核心定义 分子表达 细胞来源
Naïve多能干细胞 转录组与植入前胚胎的上胚层细胞相似,具备无限制的发育潜能,是多能性的最原始状态。可分化为所有体细胞和生殖细胞谱系 高表达:REX1、KLF2、KLF17、DPPA3
低表达:OTX2、SOX11
Primed hPSCs经外源转录因子过表达/关键信号通路调控诱导获得
Formative多能干细胞 Naïve向primed的过渡状态,转录组与植入后胚胎上胚层相似,可响应原始生殖细胞诱导、具备嵌合能力、无谱系预启动,是胚胎上胚层启动分化前的关键状态 高表达:SOX12、FZD2
下调:KLF4、KLF17、TFCP2L1
上调:SOX1、OTX2
Naïve hPSC抑制WNT/RA信号通路诱导获得;
Primed hPSCs激活FGF、TGF-β和WNT/β-catenin信号通路诱导获得
Primed多能干细胞 转录组与植入后胚胎上胚层细胞相似,受胚外组织诱导信号作用,处于准备分化的状态。分化潜能更偏向体细胞谱系,缺乏生殖系嵌合能 高表达:OTX2、FGF5、SOX11、ZIC3、DUSP6
低表达:OCT4、SOX2、NANOG
常规hPSCs培养
扩展多能干细胞(hEPSCs) 具有分化为胚胎和胚外谱系双向潜能的hPSCs,是介于多能干细胞和全能干细胞之间的细胞类型 高表达:ZSCAN4、OCT4、SOX2、NANOG Primed hPSCs转化获得;人囊胚在特异性培养基中诱导获得
8细胞样细胞(8CLCs) 模拟人类8细胞胚胎分子和表观遗传特征的类全能干细胞,展现体外实验性全能性 高表达:DUX4、TPRX1、HERVL、MLT2A1
下调:核心多能性基因
Naïve hPSC中天然存在的稀有瞬时亚群;通过DUX4过表达或表观遗传药物3-去氮腺嘌呤A诱导获得
人全能性卵裂球样细胞(hTBLCs) 经剪接体抑制等方法诱导形成的、呈现前ZGA状态的人类全能样干细胞,模拟人类受精卵及2C-4C卵裂球特征 高表达:ZBTB16、ZNF337、L1P5、LTR18A
下调:多能性相关基因
抑制:DUXA/B、TPRX1
hPSCs经剪接体抑制剂PlaB短暂处理,MYCP培养基中长期培养诱导获得
图1 干细胞与人类早期胚胎关系注:hTBLCs为人全能性卵裂球样细胞;8CLCs为8细胞样细胞;hEPSCs为人扩展多能干细胞;Naïve/Formative/Primed hESC为原始态/形成态/始发态的人类胚胎干细胞
1
Płusa B, Piliszek A. Common principles of early mammalian embryo self-organisation[J]. Development, 2020, 147(14):dev183079.
2
Iwamoto-Stohl LK, Petelski AA, Quan B, et al. Fertilization triggers early proteomic symmetry breaking in mammalian embryos[J]. Cell, 2025, 188(26):7428-7444.e21.
3
Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts[J]. Science, 1998, 282(5391): 1145-1147.
4
Du P, Wu J. Hallmarks of totipotent and pluripotent stem cell states[J]. Cell Stem Cell, 2024, 31(3):312-333.
5
Li W, Wei W, Zhu S, et al. Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors[J]. Cell Stem Cell, 2009, 4(1):16-19.
6
Theunissen TW, Powell BE, Wang H, et al. Systematic identification of culture conditions for induction and maintenance of naïve human pluripotency[J]. Cell Stem Cell, 2014,15(4):524-526.
7
Chan YS, Göke J, Ng JH, et al. Induction of a human pluripotent state with distinct regulatory circuitry that resembles preimplantation epiblast[J]. Cell Stem Cell, 2013, 13(6):663-675.
8
Ware CB, Nelson AM, Mecham B, et al. Derivation of naïve human embryonic stem cells[J]. Proc Natl Acad Sci USA, 2014,111(12):4484-4489.
9
Duggal G, Warrier S, Ghimire S, et al. Alternative routes to induce naïve pluripotency in human embryonic stem cells[J]. Stem Cells, 2015, 33(9):2686-2698.
10
Zimmerlin L, Park TS, Huo JS, et al. Tankyrase inhibition promotes a stable human naïve pluripotent state with improved functionality[J]. Development, 2016, 143(23):4368-4380.
11
Szczerbinska I, Gonzales KAU, Cukuroglu E, et al. A chemically defined feeder-free system for the establishment and maintenance of the human naïve pluripotent state[J]. Stem Cell Reports, 2019, 13(4):612-626.
12
Taei A, Kiani T, Taghizadeh Z, et al. Temporal activation of LRH-1 and RAR-γ in human pluripotent stem cells induces a functional naïve-like state[J]. EMBO Reports, 2020,21(10):e47533.
13
Bayerl J, Ayyash M, Shani T, et al. Principles of signaling pathway modulation for enhancing human naïve pluripotency induction[J]. Cell Stem Cell, 2021, 28(9):1549-1565.e12.
14
Bi Y, Hu J, Wu T, et al. Optimized derivation and culture system of human naïve pluripotent stem cells with enhanced DNA methylation status and genomic stability[J]. Protein Cell, 2025, 16(10):858-872.
15
Guo G, von Meyenn F, Santos F, et al. Naïve pluripotent stem cells derived directly from isolated cells of the human inner cell mass[J]. Stem Cell Reports, 2016,6(4):437-446.
16
Yoneyama Y, Zhang RR, Maezawa M, et al. Intercellular mRNA transfer alters the human pluripotent stem cell state[J]. Proc Natl Acad Sci USA, 2025, 122(4):e2413351122.
17
Gafni O, Weinberger L, Mansour AA, et al. Derivation of novel human ground state naïve pluripotent stem cells[J]. Nature, 2013, 504(7479): 282-286.
18
Rostovskaya M, Stirparo GG, Smith A. Capacitation of human naïve pluripotent stem cells for multi-lineage differentiation[J]. Development, 2019, 146(7):dev172916.
19
Io S, Kabata M, Iemura Y, et al. Capturing human trophoblast development with naïve pluripotent stem cells in vitro[J]. Cell Stem Cell, 2021, 28(6):1023-1039.e13.
20
Sasaki H, Sasaki I, Nichols J, et al. Generation of blastoids from human naïve pluripotent stem cells[J]. Methods Mol Biol, 2025.
21
Kinoshita M, Barber M, Mansfield W, et al. Capture of mouse and human stem cells with features of formative pluripotency[J]. Cell Stem Cell, 2021, 28(3):453-471.e8.
22
Yu L, Wei Y, Sun HX, et al. Derivation of intermediate pluripotent stem cells amenable to primordial germ cell specification[J]. Cell Stem Cell, 2021, 28(3):550-567.e12.
23
Yoshihara M, Kere J. Transcriptomic differences between human 8-cell-like cells reprogrammed with different methods[J]. Stem Cell Reports, 2023, 18(8):1621-1628.
24
Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors[J]. Cell, 2007, 131(5):861-872.
25
Brons I GM, Smithers LE, Trotter MWB, et al. Derivation of pluripotent epiblast stem cells from mammalian embryos[J]. Nature, 2007, 448(7150):191-195.
26
Tesar PJ, Chenoweth JG, Brook FA, et al. New cell lines from mouse epiblast share defining features with human embryonic stem cells[J]. Nature, 2007, 448(7150):196-199.
27
Vallier L, Alexander M, Pedersen RA. Activin/Nodal and FGF pathways cooperate to maintain pluripotency of human embryonic stem cells[J]. J Cell Sci, 2005, 118(Pt 19):4495-4509.
28
Ludwig TE, Levenstein ME, Jones JM, et al. Derivation of human embryonic stem cells in defined conditions[J]. Nat Biotechnol, 2006, 24(2):185-187.
29
Reubinoff BE, Pera MF, Fong CY, et al. Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro[J]. Nat Biotechnol, 2000, 18(4):399-404.
30
Guo G, von Meyenn F, Rostovskaya M, et al. Epigenetic resetting of human pluripotency[J]. Development, 2017, 144(15): 2748-2763.
31
Yoo DH, Im YS, Oh JY, et al. DUSP6 is a memory retention feedback regulator of ERK signaling for cellular resilience of human pluripotent stem cells in response to dissociation[J]. Sci Rep, 2023,13(1):5683.
32
Silva SS, Rowntree RK, Mekhoubad S, et al. X-chromosome inactivation and epigenetic fluidity in human embryonic stem cells[J]. Proc Natl Acad Sci USA, 2008, 105(12):4820-4825.
33
Varzideh F, Gambardella J, Kansakar U, et al. Molecular mechanisms underlying pluripotency and self-renewal of embryonic stem cells[J].Int J Mol Sci, 2023, 24(9):8386.
34
Liu B, Chen S, Xu Y, et al. Chemically defined and xeno-free culture condition for human extended pluripotent stem cells[J]. Nat Commun, 2021, 12(1):3017.
35
Yang Y, Liu B, Xu J, et al. Derivation of pluripotent stem cells with in vivo embryonic and extraembryonic potency[J]. Cell, 2017,169(2):243-257.e25.
36
Chen ACH, Lee YL, Ruan H, et al. Expanded potential stem cells from human embryos have an open chromatin configuration with enhanced trophoblast differentiation ability[J]. Adv Sci (Weinh), 2023, 10(11): e2204797.
37
Ruan D, Chen ACH, Tam TTKK, et al. Establishment of human expanded potential stem cell lines via preimplantation embryo cultivation and somatic cell reprogramming[J]. Nat Protoc, 2025, 20(10):2698-2734.
38
Taubenschmid-Stowers J, Rostovskaya M, Santos F, et al. 8C-like cells capture the human zygotic genome activation program in vitro[J]. Cell Stem Cell, 2022, 29(3):449-459.e6.
39
Yu X, Liang S, Chen M, et al. Recapitulating early human development with 8C-like cells[J]. Cell Rep, 2022, 39(12):110994.
40
Mazid MA, Ward C, Luo Z, et al. Rolling back human pluripotent stem cells to an eight-cell embryo-like stage[J]. Nature, 2022, 605(7909):315-324.
41
Zhang J, Ataei L, Mittal K, et al. LINE1 and PRC2 control nucleolar organization and repression of the 8C state in human ESCs[J]. Dev Cell, 2025, 60(2):186-203.e13.
42
Kong X, Jiang N, Chen S, et al. OTX2 inhibits human pluripotent stem cell reprogramming toward 8-cell-like and morula-like states[J]. Nat Commun, 2026, 17(1):1685.
43
Li S, Yang M, Shen H, et al. Capturing totipotency in human cells through spliceosomal repression[J]. Cell, 2024, 187(13):3284-3302.e23.
44
Shen H, Yang M, Li S, et al. Mouse totipotent stem cells captured and maintained through spliceosomal repression[J]. Cell, 2021, 184(11): 2843-2859.e20.
45
Li S, Shen H, Peng B, et al. Exploring the origin of the development: totipotent stem cells[J]. Curr Opin Genet Dev, 2025, 94:102377.
46
Zhu X, Chang Z, Xiao W, et al. N6-methyladenosine on L1PA governs the trans-silencing of LTRs and restrains totipotency in naïve human embryonic stem cells[J]. Cell Stem Cell, 2025, 32(11):1773-1791.e13.
47
Kagawa H, Javali A, Khoei H H, et al. Human blastoids model blastocyst development and implantation[J]. Nature, 2022, 601(7894): 600-605.
48
Yanagida A, Spindlow D, Nichols J, et al. Naïve stem cell blastocyst model captures human embryo lineage segregation[J]. Cell Stem Cell, 2021, 28(6):1016-1022.e4.
49
Fan Y, Min Z, Alsolami S, et al. Generation of human blastocyst-like structures from pluripotent stem cells[J]. Cell Discov, 2021, 7(1):81.
50
Yu L, Logsdon D, Pinzon-Arteaga CA, et al. Large-scale production of human blastoids amenable to modeling blastocyst development and maternal-fetal cross talk[J]. Cell Stem Cell, 2023, 30(9):1246-1261.e9.
51
Zhao C, Plaza Reyes A, Schell JP, et al. A comprehensive human embryo reference tool using single-cell RNA-sequencing data[J]. Nat Methods, 2025, 22(1):193-206.
52
Minn KT, Dietmann S, Waye SE, et al. Gene expression dynamics underlying cell fate emergence in 2D micropatterned human embryonic stem cell gastruloids[J]. Stem Cell Reports, 2021, 16(5): 1210-1227.
53
Weatherbee BAT, Gantner CW, Iwamoto-Stohl LK, et al. Pluripotent stem cell-derived model of the post-implantation human embryo[J]. Nature, 2023, 622(7983):584-593.
54
Oldak B, Wildschutz E, Bondarenko V, et al. Complete human day 14 post-implantation embryo models from naïve ES cells[J]. Nature, 2023, 622(7983):562-573.
55
Marei HE. Smarter stem cells: how AI is supercharging iPSC technology[J]. Cell Tissue Res, 2025, 402(3):283-301.
[1] 伍秋苑, 张敏, 陈芷彦, 程妹, 陈佩贤, 黄慧琦, 杨树青, 叶国麟, 邓裕华, 熊亚明, 金亚彬, 周丹. KIF18A表达影响三阴性乳腺癌细胞恶性生物学行为[J/OL]. 中华乳腺病杂志(电子版), 2026, 20(01): 16-24.
[2] 陈庆秋, 钟玲, 张婷, 张孔涌, 桂余, 齐晓伟, 任林. IGF2BP2/CCNB2轴促进三阴性乳腺癌进展的机制研究[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(05): 287-295.
[3] 廖睿, 查天建, 刘小龙. RNA结合蛋白在糖尿病足溃疡中作用的研究进展[J/OL]. 中华损伤与修复杂志(电子版), 2026, 21(01): 75-79.
[4] 陈强, 曹胜军, 李全, 赵翠娟. 益生菌在烧伤创面愈合中作用机制的研究进展[J/OL]. 中华损伤与修复杂志(电子版), 2026, 21(01): 63-68.
[5] 李晓童, 方睿, 马健, 吴吉涛, 于胜强. 人诱导多能干细胞来源外泌体对肾缺血再灌注损伤保护作用研究[J/OL]. 中华移植杂志(电子版), 2025, 19(06): 421-430.
[6] 王辉, 张含宇, 胡乐凡, 孟文卓, 王飞, 郭建明, 郭连瑞, 谷涌泉. 诱导多能干细胞在血管再生领域的全球研究趋势可视化分析[J/OL]. 中华细胞与干细胞杂志(电子版), 2026, 16(03): 150-161.
[7] 王承伟, 李娟娟, 胡文杰, 陈致帆, 许尹. 人类21三体(47,XX/XY,+21)诱导多能干细胞的制备[J/OL]. 中华细胞与干细胞杂志(电子版), 2026, 16(01): 23-30.
[8] 刘昱圻, 陈韵岱. 诱导多能干细胞构建心脏和血管类器官研究新进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2025, 15(05): 293-300.
[9] 龚娜, 傅一飞, 王文娟, 蔡广研. 分泌型磷酸蛋白-1对肾脏缺血再灌注炎症中巨噬细胞转录组的调控作用及其机制[J/OL]. 中华肾病研究电子杂志, 2026, 15(02): 61-68.
[10] 张黎. 糖尿病足的神经外科治疗策略[J/OL]. 中华神经创伤外科电子杂志, 2025, 11(04): 205-209.
[11] 钱涛. 融合与重塑:神经调控康复一体化范式的构建与展望[J/OL]. 中华脑科疾病与康复杂志(电子版), 2026, 16(02): 65-70.
[12] 信连昌, 王景景, 符锋. 神经调控技术在难治性癫痫治疗中的研究进展[J/OL]. 中华脑科疾病与康复杂志(电子版), 2025, 15(04): 238-245.
[13] 周志勇, 姜福金, 王苏贵. 脂溶性维生素通过肠肾轴调控肾结石的机制研究进展[J/OL]. 中华临床医师杂志(电子版), 2026, 20(02): 151-157.
[14] 张俊, 何玉琼, 崔夕龙, 欧建君, 高雪屏. 从成人证据溯源:tACS干预青少年抑郁障碍的神经机制与参数优化[J/OL]. 中华临床医师杂志(电子版), 2025, 19(11): 871-876.
[15] 黄亮, 徐彬翔, 王凯, 李龙, 何琳, 高强, 赵军, 刘天. 时间干涉刺激的发展:从技术原理到临床应用[J/OL]. 中华脑血管病杂志(电子版), 2025, 19(05): 353-363.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?