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Related Concept Videos

iPS Cell Differentiation01:22

iPS Cell Differentiation

2.9K
The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
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Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

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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.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
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EPS and iPS Cells in Disease Research01:21

EPS and iPS Cells in Disease Research

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Embryonic and induced pluripotent stem cells are excellent models for disease research because of their ability to self-renew and differentiate into most cell types. Somatic cells from a patient are isolated and reprogrammed into induced pluripotent stem cells or iPSCs. These iPSCs are later differentiated into the desired cell type, which mirrors the diseased cell of the patient. In this way, disease models have been created for investigating diseases such as Down syndrome, type I diabetes,...
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Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

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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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Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

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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).
Somatic...
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Induced Pluripotent Stem Cells01:13

Induced Pluripotent Stem Cells

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Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
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Cultivate Primary Nasal Epithelial Cells from Children and Reprogram into Induced Pluripotent Stem Cells
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Epigenetic Memory: Lessons From iPS Cells Derived From Human β Cells.

Shimon Efrat1

  • 1Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Frontiers in Endocrinology
|February 15, 2021
PubMed
Summary

Induced pluripotent stem cells (iPSCs) from pancreatic cells show enhanced differentiation. This suggests reproducible epigenetic memory, offering insights for improving stem cell therapies.

Keywords:
ATAC-seqEpigenetic memoryFoxa2Islet β Cellspluripotent stem cell differentiation

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Area of Science:

  • Stem Cell Biology
  • Epigenetics
  • Developmental Biology

Background:

  • Incomplete reprogramming causes variability in induced pluripotent stem cell (iPSC) differentiation capacity.
  • The origins of this heterogeneity (stochastic events vs. genetic/cell-of-origin factors) are unclear.
  • Epigenetic memory may predispose iPSCs to differentiate into their parental cell type.

Purpose of the Study:

  • To investigate iPSCs derived from human pancreatic islet beta cells (BiPSCs) for robust beta-like cell generation.
  • To determine if BiPSCs exhibit enhanced differentiation capacity compared to other iPSC types.
  • To identify epigenetic markers associated with enhanced differentiation in BiPSCs.

Main Methods:

  • Reprogramming of human pancreatic islet beta cells and non-beta cells into iPSCs.
  • Comparative analysis of spontaneous and induced differentiation towards insulin-producing cells.
  • Genome-wide open chromatin profiling (ATAC-seq) to identify differential open chromatin sites (DOCs).
  • Bioinformatic analysis to identify enriched regulatory elements and gene associations in DOCs.

Main Results:

  • BiPSCs demonstrated enhanced and reproducible differentiation into insulin-producing cells compared to isogenic non-beta cell iPSCs and fibroblast-derived iPSCs (FiPSCs).
  • Thousands of differential open chromatin sites (DOCs) were identified between BiPSCs and FiPSCs.
  • DOCs more open in BiPSCs (Bi-DOCs) were enriched for endodermal development regulators, including FOXA2 binding sites and enhancers.
  • Bi-DOCs were associated with genes crucial for pancreas development and beta-cell function.

Conclusions:

  • This study provides evidence for reproducible epigenetic memory in BiPSCs.
  • Differential open chromatin sites in BiPSCs offer potential targets for enhancing stem cell differentiation efficiency.
  • Findings may guide strategies to improve the generation of specific cell types from pluripotent stem cells for therapeutic applications.