Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro.Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent s...Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro.Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent stem cells or somatic reprogramming intermediates.However,whether blastoids can be generated from other cell types or whether they can recapitulate postimplantation development in vitro is unknown.Here,we develop a strategy to generate human blastoids from heterogeneous intermediates with epiblast,trophectoderm,and primitive endoderm signatures of the primed-to-naïve conversion process,which resemble natural blastocysts in morphological architecture,composition of cell lineages,transcriptome,and lineage differentiation potential.In addition,these blastoids reflect many features of human peri-implantation and pregastrulation development when further cultured in an in vitro 3D culture system.In summary,our study provides an alternative strategy to generate human blastoids and offers insights into human early embryogenesis by modeling peri-and postimplantation development in vitro.展开更多
Naive pluripotent state can be obtained by several strategies from various types of cells,in which the cell fate roadmap as well as key biological events involved in the journey have been described in detail.Here,we c...Naive pluripotent state can be obtained by several strategies from various types of cells,in which the cell fate roadmap as well as key biological events involved in the journey have been described in detail.Here,we carefully explored the chromatin accessibility dynamics during the primed-to-naïve transition by adopting a dual fluorescent reporter system and the assay for transposase-accessible chromatin(ATAC)-seq.Our results revealed critical chromatin remodeling events and highlight the discordance between chromatin accessibility and transcriptional activity.We further demonstrate that the differential epigenetic modifications and transcription factor(TF)activities may play a critical role in regulating gene expression,and account for the observed variations in gene expression despite similar chromatin landscapes.展开更多
基金the Ministry of Science and Technology of China(Nos.2021YFA1102000,2021YFC2700300,2019YFA0110000,and 2018YFA0108900)the National Natural Science Foundation of China(NSFC)(Nos.31721003,32022024,32270850,32100633,31871486,32070652,and 81630035)the Science and Technology Commission of Shanghai Municipality(Nos.19JC1415300 and 21JC1405500).
文摘Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro.Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent stem cells or somatic reprogramming intermediates.However,whether blastoids can be generated from other cell types or whether they can recapitulate postimplantation development in vitro is unknown.Here,we develop a strategy to generate human blastoids from heterogeneous intermediates with epiblast,trophectoderm,and primitive endoderm signatures of the primed-to-naïve conversion process,which resemble natural blastocysts in morphological architecture,composition of cell lineages,transcriptome,and lineage differentiation potential.In addition,these blastoids reflect many features of human peri-implantation and pregastrulation development when further cultured in an in vitro 3D culture system.In summary,our study provides an alternative strategy to generate human blastoids and offers insights into human early embryogenesis by modeling peri-and postimplantation development in vitro.
基金supported by the Ministry of Science and Technology of China(2021YFA11020000,2022YFC2702200 and 2018YFA0108900)the National Natural Science Foundation of China(NSFC)(31721003,32022024,32370842,32100633,32270850,32070652 and 81630035)the Shuguang Program of the Shanghai Education Development Foundation and Shanghai Municipal Education Commission(22SG20).
文摘Naive pluripotent state can be obtained by several strategies from various types of cells,in which the cell fate roadmap as well as key biological events involved in the journey have been described in detail.Here,we carefully explored the chromatin accessibility dynamics during the primed-to-naïve transition by adopting a dual fluorescent reporter system and the assay for transposase-accessible chromatin(ATAC)-seq.Our results revealed critical chromatin remodeling events and highlight the discordance between chromatin accessibility and transcriptional activity.We further demonstrate that the differential epigenetic modifications and transcription factor(TF)activities may play a critical role in regulating gene expression,and account for the observed variations in gene expression despite similar chromatin landscapes.
