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Related Concept Videos

Methods of Nuclear Reprogramming01:24

Methods of Nuclear Reprogramming

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Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
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Alternative RNA Splicing02:18

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Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
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Somatic to iPS Cell Reprogramming01:29

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Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
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Chromatin Modification in iPS Cells01:32

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Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
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Multipotency of Hematopoietic Stem Cells01:19

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The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
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Related Experiment Video

Updated: Jun 24, 2025

RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells
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Capturing totipotency in human cells through spliceosomal repression.

Shiyu Li1, Min Yang1, Hui Shen1

  • 1MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, China.

Cell
|June 6, 2024
PubMed
Summary

Researchers cultured human totipotent blastomere-like cells (hTBLCs) by reprogramming stem cells. These hTBLCs mimic early human development and can form blastocyst-like structures, offering insights into totipotency.

Keywords:
ZGA-like cellsblastocyst-like structureblastomerepluripotentsplicing inhibitionstem cell culturetotipotencytotipotent blastomere-like cellszygotic genomic activation

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Last Updated: Jun 24, 2025

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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Genetics

Background:

  • Totipotent blastomeres, generated from zygote cleavage, are crucial for initiating human development via zygotic genome activation (ZGA).
  • Maintaining human cell totipotency in vitro presents significant challenges.
  • Existing models like 8-cell-like cells (8CLCs) have limitations in fully recapitulating totipotency.

Purpose of the Study:

  • To establish a method for culturing human totipotent blastomere-like cells (hTBLCs).
  • To investigate the characteristics and developmental potential of these novel hTBLCs.
  • To provide criteria and insights into achieving and understanding human cell totipotency.

Main Methods:

  • Reprogramming human pluripotent stem cells using splicing inhibition to generate ZGA-like cells (ZLCs).
  • Long-term passaging of ZLCs to establish stable hTBLCs.
  • Characterization of gene expression profiles, including pluripotent and ZGA-specific genes.
  • Assessing the differentiation potential of hTBLCs in vitro.

Main Results:

  • Splicing inhibition transiently generated ZLCs, which stabilized into hTBLCs after prolonged culture.
  • Both ZLCs and hTBLCs exhibited widespread silencing of pluripotent genes.
  • ZLCs activated ZGA-specific genes, while hTBLCs showed enrichment of pre-ZGA genes.
  • hTBLCs successfully recapitulated human pre-implantation development, generating epiblast (EPI), primitive endoderm (PrE), and trophectoderm (TE)-like lineages.
  • hTBLCs autonomously formed blastocyst-like structures in vitro, demonstrating both embryonic and extraembryonic developmental potency.

Conclusions:

  • The study successfully established and characterized human totipotent blastomere-like cells (hTBLCs).
  • hTBLCs represent a valuable model for studying human totipotency and early development.
  • The findings offer critical insights and criteria for achieving and understanding human cell totipotency.