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Dev Cell 2021 May 17;5610:1541-1551.e6. doi: 10.1016/j.devcel.2021.04.016.
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Fibroblast dedifferentiation as a determinant of successful regeneration.

Lin TY , Gerber T , Taniguchi-Sugiura Y , Murawala P , Hermann S , Grosser L , Shibata E , Treutlein B , Tanaka EM .

Limb regeneration, while observed lifelong in salamanders, is restricted in post-metamorphic Xenopus laevis frogs. Whether this loss is due to systemic factors or an intrinsic incapability of cells to form competent stem cells has been unclear. Here, we use genetic fate mapping to establish that connective tissue (CT) cells form the post-metamorphic frog blastema, as in the case of axolotls. Using heterochronic transplantation into the limb bud and single-cell transcriptomic profiling, we show that axolotl CT cells dedifferentiate and integrate to form lineages, including cartilage. In contrast, frog blastema CT cells do not fully re-express the limb bud progenitor program, even when transplanted into the limb bud. Correspondingly, transplanted cells contribute to extraskeletal CT, but not to the developing cartilage. Furthermore, using single-cell RNA-seq analysis we find that embryonic and adult frog cartilage differentiation programs are molecularly distinct. This work defines intrinsic restrictions in CT dedifferentiation as a limitation in adult regeneration.

PubMed ID: 34004152
PMC ID: PMC8140481
Article link: Dev Cell

Species referenced: Xenopus laevis
Genes referenced: c1qc cav1 ccl20 col1a2 col9a2 dact1 dlx5 dpt edil3 epcam fancc fgf1 gzmh hapln1 hbg1 hebp2 hoxa11 hoxa13 igfbp2 irx3 krt8.1 matn1 matn2 matn4 meis1 mmp9.1 mrc1 nog olfm4 otos plvap prrx1 reln runx1 sox10 sox4 sox8 sox9 stmn1 tagln tnc tnmd trim9 twist2
GO keywords: regeneration [+]
Antibodies: Col1a1 Ab2 Pax7 Ab2 Prrx1 Ab1

GEO Series: GSE165901: NCBI

Article Images: [+] show captions
References [+] :
Angerer, destiny: diffusion maps for large-scale single-cell data in R. 2016, Pubmed