RT Journal Article
SR Electronic
T1 Differential Expression of α, β, and γ Protocadherin Isoforms During Differentiation, Aging, and Cancer
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.07.434314
DO 10.1101/2021.03.07.434314
A1 Michael D. West
A1 Ivan Labat
A1 Jie Li
A1 Pam Sim
A1 Jeffrey Janus
A1 Hayley Mangelson
A1 Shawn Sullivan
A1 Ivan Liachko
A1 Paul Labhart
A1 Maddy Craske
A1 Brian Egan
A1 Karen B. Chapman
A1 Nafees N. Malik
A1 Dana Larocca
A1 Hal Sternberg
YR 2021
UL http://biorxiv.org/content/early/2021/03/08/2021.03.07.434314.abstract
AB The cadherin family of cell surface glycoproteins plays a fundamental role in cell-cell recognition, thereby participating in diverse biological process such as embryonic morphogenesis and oncogenic transformation. The subset of clustered protocadherin (PCDH) genes generated from the α, β, and γ loci, have been widely studied for their potential role in neuronal cell-cell recognition and neurogenesis, however their broader role in normal embryonic development and cancer has not been examined in detail. We utilized human embryonic stem (hES) cells to model early human development in vitro, comparing PCDH isoform transcription in diverse types of embryonic progenitors with normal adult-derived and cancer counterparts. Embryonic progenitors express genes from the α and β cluster at levels comparable to that seen in the CNS, while fetal and adult-derived cells express primarily from the γ cluster. Replicative senescence left fibroblasts with markedly lower expression of all isoforms. We observe that an embryonic pattern of clustered protocadherin gene expression and associated CpG island methylation is commonly associated with cancer cell lines from diverse tissue types. The differential regulation of the α, β, and γ loci coincide with alternate regions of DNA accessibility at CTCF binding sites and lamina-associated domains and CPL expression correlated with the expression of LMNA and LMNB1. These observations support a potential role for the differential regulation of genes within the clustered protocadherin locus in selective cell-cell adhesion during embryogenesis, regeneration, cancer and aging.Competing Interest StatementHS, IL, JL, PS, JJ, DL and MDW are employees of and stockholders in AgeX, Inc., (Alameda, CA). KBC is an employee of Eclipse Innovations, (San Diego, CA) and a stockholder of AgeX, Inc.