Figure 1.

Heterogeneity of cell phenotype and identity in neuroblastoma cell lines. (A) The SK-N-SH cell line is heterogeneous with two distinct populations. The N-type population is constituted by cells with neurites, expressing the noradrenergic enzymes tyrosine hydroxylase (TH) and dopamine-β-hydroxylase (DBH) and markers such as enolase, chromogranins, neurofilaments (NF) proteins, or the NGF receptor. The S-type population includes substrate-adherent cells expressing markers including vimentin (VIM), fibronectin (FN1), β2-microglobulin, extracellular matrix (ECM) proteins, or HLA class 1 antigens. (B) Sub-lines derived from the heterogeneous SK-N-SH. The thrice-cloned SH-SY5Y sub-line presents an N-phenotype with a karyotype with a duplication of the chromosome 1q (dup(1q)), whereas the SH-EP sub-line presents an S-phenotype with an isochromosome 1q (i(1q)) in 35% of the cells. Interestingly, both cell types can undergo a spontaneous bidirectional interconversion. (C) Analysis of the SE landscape of the SK-N-SH, SH-SY5Y, and SH-EP cell lines revealed that epigenetic regulation shapes cellular identity (principal component analysis based on super-enhancer scores. Image is from “Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries” by Boeva, V. et al., 2017, Nature Genetics, 49, 1408–1413, Reprinted with permission from Ref. [19]. Copyright 2021 Springer Nature). The SH-SY5Y cell line is included in group I corresponding to a noradrenergic identity, while the SH-EP cell line is in group II, close to human NCC lines. The heterogeneous SK-N-SH cell line is included in an intermediate group. The different phenotypes of the cells of the corresponding cell lines are shown by immunofluorescence with Phalloïdin (green) and DAPI (blue). Scale bar = 20 µm.