Chromatin accessibility dynamics and single cell RNA-Seq reveal new regulators of regeneration in neural progenitors

eLife, 2020 · DOI: https://doi.org/10.7554/eLife.52648 · Published: April 27, 2020

Genetics Bioinformatics Regenerative Medicine & Stem Cells

Simple Explanation

Vertebrate appendage regeneration requires precisely coordinated remodeling of the transcriptional landscape to enable the growth and differentiation of new tissue, a process executed over multiple days and across dozens of cell types. To better understand how a regenerative program is fulfilled by neural progenitor cells (NPCs) of the spinal cord, we analyzed pax6-expressing NPCs isolated from regenerating Xenopus tropicalis tails. Overall, we use transcriptional regulatory dynamics to present a new model for cell fate decisions and their regulators in NPCs during regeneration.

Study Duration

Not specified

Participants

Xenopus tropicalis tadpoles

Evidence Level

Not specified

Key Findings

1
NPCs place an early priority on neuronal differentiation. Late in regeneration, the priority returns to proliferation.
2
Pbx3 and Meis1 as critical regulators of tail regeneration and axon organization.
3
The overall chromatin accessibility of NPCs is readily distinguished from bulk tissue and strongly reflects their distinct neural character.

Research Summary

By intersecting chromatin accessibility data with single-cell transcriptomics, we find that NPCs place an early priority on neuronal differentiation. Late in regeneration, the priority returns to proliferation. Our analyses identify Pbx3 and Meis1 as critical regulators of tail regeneration and axon organization.

Practical Implications

New regulatory factors and target genes

Neural lineage-specific analysis of regeneration identifies new regulatory factors and target genes.

Temporal uncoupling of differentiation and proliferation

There is evidence for a temporal uncoupling of differentiation and proliferation in the regenerating neural lineage.

Neural cell type identity

Neural cell types preserve their identities in the regenerating Xenopus tail.

Study Limitations

1
Not every NPC may have been captured
2
Some cells that were recently pax6+ neural progenitors, and are now differentiating but retain GFP protein may have been captured.
3
The very small size and delicacy of the regeneration bud at 24hpa precluded verification that Sox2 and pax6:GFP colocalize in the same way during the early stages of regeneration as the neural ampulla forms.

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