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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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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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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 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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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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Related Experiment Video

Updated: Mar 7, 2026

Chemical Reversion of Conventional Human Pluripotent Stem Cells to a Naïve-like State with Improved Multilineage Differentiation Potency
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Tracking the embryonic stem cell transition from ground state pluripotency.

Tüzer Kalkan1, Nelly Olova2, Mila Roode3

  • 1Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Cambridge CB2 1QR, UK tk360@cam.ac.uk austin.smith@cscr.cam.ac.uk.

Development (Cambridge, England)
|February 9, 2017
PubMed
Summary

Mouse embryonic stem cells (ESCs) transition from naïve pluripotency through a distinct formative state before lineage priming. This transition involves rapid loss of ESC identity and increased DNA methylation.

Keywords:
ES cellsEpiblastMethylomePluripotencyRex1Transcriptome

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Oct4GiP Reporter Assay to Study Genes that Regulate Mouse Embryonic Stem Cell Maintenance and Self-renewal
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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Epigenetics

Background:

  • Embryonic stem (ES) cells maintain self-renewal by avoiding differentiation cues.
  • Understanding the transition from naïve pluripotency is key to developmental studies.
  • Previous research has not fully delineated the initial exit from the naïve state.

Purpose of the Study:

  • To investigate the early transition process of mouse ES cells exiting naïve pluripotency.
  • To characterize the cellular and epigenetic changes during this critical developmental window.
  • To distinguish between early post-implantation epiblast and primed epiblast states.

Main Methods:

  • Utilized a short-half-life Rex1::GFP reporter to track cells exiting naïve pluripotency.
  • Analyzed asynchronous cell populations to isolate distinct developmental stages.
  • Assessed pluripotency factor expression and lineage specification markers.
  • Quantified genome-wide DNA methylation levels.

Main Results:

  • Single-cell identity loss from the naïve state is abrupt and asynchronous.
  • Exit from naïve pluripotency precedes lineage marker appearance.
  • Cells transitioning from the ES cell state resemble early post-implantation epiblast, not primed epiblast.
  • A genome-wide increase in DNA methylation was observed, intermediate between early and late epiblast.

Conclusions:

  • Naïve pluripotent cells transition through a distinct formative phase.
  • This formative phase is preparatory to lineage priming.
  • The findings support a model of developmental progression from naïve pluripotency through a formative state.