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Related Concept Videos

Lineage Commitment01:21

Lineage Commitment

Commitment is the  process whereby stem cells:
Cell Signaling Feedback Loops01:07

Cell Signaling Feedback Loops

Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
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During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In contrast, determination...
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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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Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...
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Related Experiment Video

Updated: Jul 3, 2026

Differentiation of a Human Neural Stem Cell Line on Three Dimensional Cultures, Analysis of MicroRNA and Putative Target Genes
10:48

Differentiation of a Human Neural Stem Cell Line on Three Dimensional Cultures, Analysis of MicroRNA and Putative Target Genes

Published on: April 12, 2015

A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment.

Agnieszka Rybak1, Heiko Fuchs, Lena Smirnova

  • 1Institute of Cell and Neurobiology, Center for Anatomy, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Nature Cell Biology
|July 8, 2008
PubMed
Summary

MicroRNAs let-7 and mir-125 are crucial for neural stem cell differentiation. The Lin-28 protein inhibits their processing, but is downregulated by let-7 and mir-125 in neural stem cells, forming a regulatory circuit.

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Published on: January 12, 2015

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Stem Cell Biology

Background:

  • MicroRNA (miRNA) populations, including mammalian homologues of lin-4 (mir-125) and let-7, undergo significant changes during stem-cell differentiation.
  • mir-125 and let-7 are known to be induced during the neural differentiation of embryonic stem (ES) cells and embryocarcinoma (EC) cells.

Purpose of the Study:

  • To investigate the post-transcriptional mechanisms regulating let-7 induction during neural stem cell differentiation.
  • To elucidate the role of the pluripotency factor Lin-28 in miRNA processing and its interaction with let-7 and mir-125.

Main Methods:

  • Analysis of miRNA expression in embryonic neural stem (NS) cells.
  • Investigation of Lin-28 binding to pre-let-7 RNA.
  • Assessment of Dicer ribonuclease activity in ES, EC, and NS cells.
  • Functional assays involving suppression of let-7 or mir-125 activity in NS cells.

Main Results:

  • Embryonic neural stem (NS) cells express let-7 and mir-125.
  • The pluripotency factor Lin-28 binds to pre-let-7 RNA, inhibiting its processing by Dicer in ES and EC cells.
  • In NS cells, Lin-28 is downregulated by mir-125 and let-7, which permits pre-let-7 processing.
  • Suppression of let-7 or mir-125 in NS cells resulted in Lin-28 upregulation and reduced pre-let-7 processing.

Conclusions:

  • let-7, mir-125, and Lin-28 form an autoregulatory circuit that governs miRNA processing during neural stem cell commitment.
  • This circuit plays a critical role in the transition of miRNA populations during stem cell differentiation.