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

doi:10.3877/cma.j.issn.2095-1221.2026.03.007

Abstract

Abstract:

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.

Key words: Pluripotent stem cells, Totipotent stem cells, Developmental potential, In vitro embryo models, Pluripotency, Regulation

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

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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

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

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