Targeted Deletion in the Basal Body Protein Talpid3 Leads to Loss of Primary Cilia in Embryonic Stem Cells and Defective Lineage-Specific Differentiation

Talpid3 is a basal body protein required for the formation of primary cilia, an organelle involved in signal transduction. Here, we asked if Talpid3 has a role in the regulation of differentiation and/or self-renewal of ES cells and whether cells lacking cilia due to a deletion in Talpid3 can be rep...

Full description

Saved in:
Bibliographic Details
Main Authors: Ross Ferguson, Vasanta Subramanian
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/13/23/1957
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Talpid3 is a basal body protein required for the formation of primary cilia, an organelle involved in signal transduction. Here, we asked if Talpid3 has a role in the regulation of differentiation and/or self-renewal of ES cells and whether cells lacking cilia due to a deletion in Talpid3 can be reprogrammed to induced pluripotent stem (iPS) cells. We show that mouse embryonic limb fibroblasts which lack primary cilia with a targeted deletion in the <i>Talpid3</i> (<i>Ta3</i>) gene can be efficiently reprogrammed to iPS cells. Furthermore, vector-free <i>Ta3<sup>−/−</sup></i> iPS cells retain ES cell features and are able to self-renew. However, both <i>Ta3<sup>−/−</sup></i> iPS and ES cells are unable to form visceral endoderm and differentiate poorly into neurons. The observed defects are not a consequence of reprogramming since <i>Ta3<sup>−/−</sup></i> ES cells also exhibit this phenotype. Thus, Talpid3 and primary cilia are required for some differentiation events but appear to be dispensable for stem cell self-renewal and reprogramming.
ISSN:2073-4409