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Transcription Attenuation in Prokaryotes02:42

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Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure.  Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
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Mitigating xenogeneic barriers to chimerism through Cas13-induced host attenuation.

Bingbing He1, Shijian Lv2, Leijie Li1

  • 1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Developmental Cell
|January 30, 2026
PubMed
Summary

Researchers used Cas13 to reduce host cell proliferation, enhancing human stem cell integration in animal embryos. This strategy overcomes barriers for interspecies organ generation and developmental studies.

Keywords:
Cas13blastocyst complementationcell competitionchimerascollateral cleavageembryonic stem cellsinduced pluripotent stem cellsxenogeneic barriers

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Induction and Scoring of Graft-Versus-Host Disease in a Xenogeneic Murine Model and Quantification of Human T Cells in Mouse Tissues using Digital PCR
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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Biotechnology

Background:

  • Interspecies chimeras are crucial for studying mammalian development and organ generation.
  • Xenogeneic barriers like developmental timing and cell competition limit human pluripotent stem cell (hPSC) contribution to non-human embryos.

Purpose of the Study:

  • To develop a method to overcome xenogeneic barriers and enhance donor cell chimerism.
  • To investigate the use of Cas13 to modulate host cell proliferation and improve interspecies developmental potential.

Main Methods:

  • Engineered mouse epiblast stem cells (mEpiSCs) with inducible Cas13 (iCas13).
  • Utilized Cas13's collateral RNA cleavage to selectively attenuate host cell proliferation.
  • Performed co-culture and in vivo chimera experiments with wild-type and engineered cells, including hPSCs.

Main Results:

  • Cas13 activation in mEpiSCs reduced proliferation and bystander transcripts while maintaining pluripotency.
  • Selective host cell attenuation enhanced the competitiveness and survival of donor cells (mEpiSCs and hPSCs) in vitro.
  • Blastocysts with iCas13 demonstrated increased donor cell integration in chimeric embryos and adult tissues.

Conclusions:

  • Cas13-mediated host cell attenuation is a viable strategy to boost donor cell chimerism.
  • This approach effectively mitigates xenogeneic barriers in interspecies developmental models.
  • The findings offer a generalizable method for advancing interspecies organogenesis and developmental research.