Response to Kildsiute et al. and Bedoya-Reina and Schlisio

We appreciate Kildsiute et al. and Bedoya-Reina Schlisio for their attention to our work comments on publication (Dong al., 2020Dong R. Yang Zhan Y. Lai H.D. Ye C.J. Yao X.Y. Luo W.Q. Cheng X.M. Miao J.J. Wang J.F. al.Single-cell characterization of malignant phenotypes developmental trajectories adrenal neuroblastoma.Cancer Cell. 2020; 38: 716-733Abstract Full Text PDF PubMed Scopus (49) Google Scholar). believe letters response will be interest the neuroblastoma neural development communities as well many bioinformaticians. In “Pitfalls Applying Mouse Markers Human Adrenal Medullary Cells” “Chromaffin Cells with Sympathoblast Signature: Too Similar Keep Apart?” (Kildsiute 2020Kildsiute G. Young M.D. Behjati S. Pitfalls applying mouse markers human medullary cells.Cancer 39https://doi.org/10.1016/j.ccell.2020.12.006Abstract (5) Scholar) (Bedoya-Reina Schlisio, 2020Bedoya-Reina O.C. Chromaffin cells sympathoblast signature: too similar keep apart?.Cancer 39https://doi.org/10.1016/j.ccell.2020.12.009Abstract argue definition cell types in paper describing single-cell RNA sequencing fetal gland They both expressed concerns about type annotation sympathoadrenal lineage, particular chromaffin sympathoblasts, after comparing datasets transcriptional characteristics murine (Furlan 2017Furlan A. Dyachuk V. Kastriti M.E. Calvo-Enrique L. Abdo H. Hadjab Chontorotzea T. Akkuratova N. Usoskin D. Kamenev al.Multipotent peripheral glial generate neuroendocrine medulla.Science. 2017; 357: eaal3753Crossref (146) used computational methods examine cellular identity cells, according reference data. showed that we may reversely identify sympathoblasts. don’t question approaches analyses. Our basic view is direct transfer information tends less rigorous. lineage share features common, especially at early stages (Huber, 2006Huber K. The lineage: specification, diversification, new perspectives.Dev. Biol. 2006; 298: 335-343Crossref (139) For example, express well-known such TH CHGA/CHGB factors GATA2, GATA3, HAND2, indicated Figure 3C addition, expression patterns certain are highly dynamic during development. sympathetic neurons downregulate DBH lose late Therefore, it risky if completely follow previous studies without considering cross-species time issues. study, first looked differential genes can distinguish these two types. By studying marker sympathoblasts from literature, learned CARTPT specifically (Chan 2016Chan W.H. Gonsalvez D.G. H.M. Southard-Smith E.M. Cane K.N. Anderson C.R. Differences CART cycle behavior discriminate neuroblast lineages cells.Dev. Neurobiol. 2016; 76: 137-149Crossref (15) Scholar; Furlan 2019Kastriti Kameneva P. Hampl M. Memic F. Marklund U. Lallemend al.Schwann precursors majority zuckerkandl organ some paraganglia.Front. Mol. Neurosci. 2019; 12: 6Crossref (40) seems more dependent PHOX2B, a homeodomain transcription factor, which has been previously shown by analysis loss-of-function experiments (Huber 2005Huber Karch Ernsberger Goridis C. Unsicker role Phox2B development.Dev. 2005; 279: 501-508Crossref (59) Consistent studies, data CARTPT+ have relatively low PHOX2B (Figure S1A). Most importantly, distinct spatial locations. mainly locate extra-adrenal sites (sympathetic ganglion suprarenal ganglion), but not medulla contrast, located confirmed locations main immunofluorescence staining CARTPT. only detected sites. PHOX2B+ found site, corresponding chromaffin, respectively (Figures S1B S1C). conclusion, was based bioinformatic experimental validation. Download .pdf (.58 MB) Help pdf files Document S1. S1 Apart?Bedoya-Reina al.Cancer CellDecember 31, 2020In BriefDong (2020) built an atlas developing crest derivatives humans trace origins neuroblastoma. compared anlagen clusters designated resemble mouse. Full-Text Open ArchiveSingle-Cell Characterization Malignant Phenotypes Developmental Trajectories NeuroblastomaDong CellSeptember 17, provide detailed phenotypic landscape (NB) using show proliferation/differentiation status associated clinical heterogeneity NB. ArchivePitfalls CellsKildisiute BriefIn this letter, re-analyze generated Dong demonstrate pitfalls relying annotate unbiased label imply had suggested. ArchiveEvolutionary switch key between leads mis-assignment medullaKameneva CellApril 29, 2021In BriefWe would like clarify aspects ongoing discussion 2021; Kildisiute 2021b; 2021) regarding recent study 2020), authors performed transcriptomics medulla, followed comparison heterogeneous populations. grateful publishing valuable data, communal interpretation context embryos pathological tissues. Archive