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Direct Reprogramming of Non-limb Fibroblasts to Cells with Properties of Limb Progenitors

Authors :
Joshua M. Gorham
Christine E. Seidman
Vannier J
Charlotte Colle
Patrick Tschopp
Olivier Pourquié
Chao-Zong Lee
Yuji Atsuta
Clifford J. Tabin
Jon G. Seidman
Alan R. Rodrigues
Reiko R. Tomizawa
Lujan Eg
Publication Year :
2021
Publisher :
Cold Spring Harbor Laboratory, 2021.

Abstract

SUMMARYThe early limb bud consists of mesenchymal progenitors (limb progenitors) derived from the lateral plate mesoderm (LPM) that produce most of the tissues of the mature limb bud. The LPM also gives rise to the mesodermal components of the trunk, flank and neck. However, the mesenchymal cells generated at these other axial levels cannot produce the variety of cell types found in the limb bud, nor can they be directed to form a patterned appendage-like structure, even when placed in the context of the signals responsible for organizing the limb bud. Here, by taking advantage of a direct reprogramming approach, we find a set of factors (Prdm16, Zbtb16, and Lin28) normally expressed in the early limb bud, that are capable of imparting limb progenitor-like properties to non-limb fibroblasts. Cells reprogrammed by these factors show similar gene expression profiles, and can differentiate into similar cell types, as endogenous limb progenitors. The further addition of Lin41 potentiates proliferation of the reprogrammed cells while suppressing differentiation. These results suggest that these same four key factors may play pivotal roles in the specification of endogenous limb progenitors.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........cc51e2b26b294d1e9b082bbab009b07b
Full Text :
https://doi.org/10.1101/2021.10.01.462632