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Related Concept Videos

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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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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Embryonic Stem Cells00:58

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Embryonic stem (ES) cells are undifferentiated pluripotent cells, meaning they can produce any cell type in the body. This gives them tremendous potential in science and medicine since they can generate specific cell types for use in research or to replace body cells lost due to damage or disease.
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Embryonic Stem Cells00:57

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Embryonic stem (ES) cells were first discovered in mice in 1981 by Martin Evans. In 1998, James Thomson identified a method to isolate embryonic stem cells from humans. Human embryonic stem cells (hESCs) are obtained from 3-5 day old embryos that remain unused after an in vitro fertilization procedure.
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Adult Stem Cells01:33

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Stem cells are undifferentiated cells that divide and produce more stem cells or progenitor cells that differentiate into mature, specialized cell types. All the cells in the body are generated from stem cells in the early embryo, but small populations of stem cells are also present in many adult tissues including the bone marrow, brain, skin, and gut. These adult stem cells typically produce the various cell types found in that tissue—to replace cells that are damaged or to continuously...
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iPS Cell Differentiation01:22

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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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Updated: Feb 14, 2026

Efficient Differentiation of Human Pluripotent Stem Cells into Liver Cells
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A Roadmap for Human Liver Differentiation from Pluripotent Stem Cells.

Lay Teng Ang1, Antson Kiat Yee Tan1, Matias I Autio2

  • 1Stem Cell & Regenerative Biology Group, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore.

Cell Reports
|February 22, 2018
PubMed
Summary

Human pluripotent stem cells (hPSCs) can generate liver progenitors by dynamically controlling extracellular signals. This developmental biology approach efficiently produces liver cells, improving survival in a mouse model of liver failure.

Keywords:
efficient differentiationhuman liver developmentpluripotent stem cellsprogenitorsignaling

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Area of Science:

  • Developmental biology
  • Stem cell research
  • Hepatology

Background:

  • Closely related endodermal lineages like liver, pancreas, and intestines diversify from a common origin.
  • Understanding lineage restriction during differentiation is crucial for regenerative medicine.

Purpose of the Study:

  • To reconstitute liver progenitors from human pluripotent stem cells (hPSCs) using developmental biology principles.
  • To map the diversification of endodermal lineages and identify key signaling pathways for liver commitment.

Main Methods:

  • Applying developmental biology principles to hPSCs to generate liver progenitors.
  • Mapping endodermal lineage formation and identifying signaling combinations (inductive and repressive) that dictate cell fate.
  • Temporally manipulating extracellular signals (retinoid, WNT, TGF-β) across six developmental junctures.

Main Results:

  • Identified that alternate endodermal fates are restricted during liver commitment.
  • Demonstrated that human liver fate is determined by specific doses and temporal combinations of extracellular signals.
  • Achieved efficient generation of 94.1% ± 7.35% TBX3+HNF4A+ liver bud progenitors by day 6 and 81.5% ± 3.2% FAH+ hepatocyte-like cells by day 18.
  • Showcased improved short-term survival of differentiated cells in a mouse model of liver failure.

Conclusions:

  • Temporal dynamics of signaling interpretation are critical for directing hPSC differentiation towards specific endodermal lineages.
  • Dynamic manipulation of extracellular signals provides an efficient strategy for generating human liver progenitors and hepatocyte-like cells.
  • This approach holds promise for advancing liver regenerative medicine and disease modeling.