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Embryonic Stem Cells00:58

Embryonic Stem Cells

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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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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Transcriptional landscape changes during human embryonic stem cell derivation.

S Warrier1, J Taelman1, L Tilleman2

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Molecular Human Reproduction
|September 22, 2018
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The post-inner cell mass intermediate (PICMI) stage in human embryonic stem cell (hESC) derivation is a crucial transition point. This stage exhibits unique gene expression patterns, including primordial germ cell (PGC) markers, influencing pluripotency and differentiation potential.

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Area of Science:

  • * Developmental Biology
  • * Stem Cell Biology
  • * Genomics

Background:

  • * Human embryonic stem cells (hESCs) are derived from the inner cell mass (ICM) of blastocysts.
  • * The post-ICM intermediate (PICMI) stage represents a transitional phase during hESC derivation.
  • * Understanding transcriptional changes during this transition is crucial for defining pluripotency states and differentiation potential.

Purpose of the Study:

  • * To investigate the transcriptional landscape changes during hESC derivation from ICM to PICMI to hESC.
  • * To elucidate the signaling mechanisms governing the ICM to PICMI to hESC transition.
  • * To define the role of the PICMI in establishing pluripotent states and differentiation potential.

Main Methods:

  • * Comparative RNA sequencing (RNA-seq) was performed on ICMs, PICMIs, and hESCs.
  • * Samples were collected in biological and technical triplicates.
  • * Statistical analysis was conducted using edgeR with a false discovery rate (FDR) < 0.05.

Main Results:

  • * Significant differences in gene expression were observed between ICM, PICMI, and hESC stages.
  • * The PICMI showed upregulation of primordial germ cell (PGC) markers and dependence on leukemia inhibitory factor (LIF) signaling.
  • * Principle component analysis indicated distinct clustering of ICM, while PICMI and hESCs were in close proximity.
  • * Upregulation of the PI3K/AKT/mTOR pathway and predisposition towards the germ cell lineage were observed in the PICMI.

Conclusions:

  • * The PICMI represents a distinct intermediate pluripotency stage during hESC derivation.
  • * The PICMI exhibits characteristics that may predispose it towards germ cell differentiation.
  • * Understanding the PICMI stage can inform strategies for enhancing naïve hESC derivation and germ cell differentiation efficiency.