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Ancestral Stem Cell Reprogramming Genes Active in Hemichordate Regeneration.

Tom Humphreys1, Keith Weiser1, Asuka Arimoto2

  • 1Institute for Biogenesis Research, University of Hawai'i at Mānoa, Honolulu, HI, United States.

Frontiers in Ecology and Evolution
|April 3, 2023
PubMed
Summary
This summary is machine-generated.

Hemichordate worms utilize key stem cell reprogramming factors for extensive regeneration, unlike chordates. This suggests ancient regeneration mechanisms may have been lost in more complex species.

Keywords:
Klf1/2/4MsxlxPou3SoxB1hemichordatesregenerationstem-cell reprogramming genes

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Area of Science:

  • Developmental Biology
  • Regenerative Medicine
  • Evolutionary Biology

Background:

  • Hemichordate worms exhibit remarkable regeneration capabilities, similar to planaria and hydra.
  • Hemichordates are phylogenetically basal deuterostomes, potentially offering insights into early deuterostome body plan evolution.
  • Extensive regeneration is uncommon in more derived deuterostomes, including chordates, mammals, and humans.

Purpose of the Study:

  • To investigate if hemichordates employ functional homologs of canonical Yamanaka stem cell reprogramming factors (Oct4, Sox2, Nanog, Klf4) during regeneration.
  • To compare the regenerative mechanisms of hemichordates with those of chordates, where these factors are not typically expressed during regeneration.

Main Methods:

  • Identified potential hemichordate homologs of Yamanaka factors (Oct4, Sox2, Nanog, Klf4) from Ptychodera flava EST libraries: Pf-Pou3, Pf-SoxB1, Pf-Msxlx, and Pf-Klf1/2/4.
  • Utilized in situ hybridization to analyze the expression patterns of these homologs during head regeneration in hemichordates.
  • Performed functional assays by testing if Pf-Pou3 could rescue Oct4-deficient mouse embryonic stem cells, assessing pluripotency gene expression.

Main Results:

  • Identified and characterized hemichordate homologs of Oct4, Sox2, Nanog, and Klf4.
  • Demonstrated distinct expression patterns of these homologs during hemichordate head regeneration.
  • Showed that Pf-Pou3 could partially maintain pluripotency gene expression in mouse embryonic stem cells lacking Oct4.

Conclusions:

  • Hemichordates may utilize reprogramming factors for extensive regeneration, or chordates might have lost this capability.
  • The conserved pluripotency gene circuits are intact in mammals and could potentially be reactivated for regeneration under specific regulatory signals.