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Related Concept Videos

Maintenance of the ES Cell State01:14

Maintenance of the ES Cell State

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The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
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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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Cellular Differentiation00:57

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How does a complex organism such as a human develop from a single cell? It all starts from a single fertilized egg which gives rise to a vast array of cell types, such as nerve cells, muscle cells, and epithelial cells that characterize the adult? Throughout development and adulthood, cellular differentiation leads cells to assume their final morphology and physiology. Differentiation is the process by which unspecialized cells become specialized to carry out distinct functions.
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Induced Pluripotent Stem Cells01:06

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Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
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Related Experiment Video

Updated: Jul 30, 2025

Chemical Reversion of Conventional Human Pluripotent Stem Cells to a Na&#239;ve-like State with Improved Multilineage Differentiation Potency
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Cellular population dynamics shape the route to human pluripotency.

Francesco Panariello1, Onelia Gagliano2,3,4, Camilla Luni5,6

  • 1Telethon Institute of Genetics and Medicine (TIGEM), Armenise/Harvard Laboratory of Integrative Genomics, Pozzuoli, Italy.

Nature Communications
|May 17, 2023
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Human cellular reprogramming to induced pluripotency is inefficient. Microfluidics and multi-omics reveal extrinsic protein communication pathways and the HGF/MET/STAT3 axis enhance reprogramming efficiency by reshaping the extracellular environment.

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Area of Science:

  • Cellular biology
  • Stem cell research
  • Biotechnology

Background:

  • Human cellular reprogramming to induced pluripotency remains inefficient, limiting the study of intermediate stages.
  • Understanding extrinsic factors influencing reprogramming is crucial for improving efficiency.

Purpose of the Study:

  • To identify and resolve distinct subpopulations and their interactions during high-efficiency reprogramming.
  • To elucidate the role of extracellular context and cell population determinants in human cellular reprogramming.

Main Methods:

  • Utilized microfluidics for high-efficiency reprogramming.
  • Performed temporal multi-omics, including secretome analysis and single-cell transcriptomics.
  • Investigated protein communication pathways and extracellular environment remodeling.

Main Results:

  • Identified functional extrinsic pathways of protein communication between reprogramming subpopulations.
  • Demonstrated the HGF/MET/STAT3 axis as a potent enhancer of reprogramming.
  • Showcased HGF accumulation in microfluidics enhances reprogramming, while exogenous supply is needed in conventional dishes.

Conclusions:

  • Human cellular reprogramming is transcription factor-driven but heavily relies on extracellular context.
  • Cell population determinants and extrinsic signaling pathways significantly impact reprogramming efficiency.
  • Microfluidic systems can optimize reprogramming by facilitating endogenous factor accumulation.