Journal
NATURE GENETICS
Volume 53, Issue 5, Pages 694-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41588-021-00818-x
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Funding
- Paradifference Foundation
- Swedish Cancer Society
- Bertil Hallsten Research Foundation
- Knut and Alice Wallenberg Foundation
- ERACoSysMed 4D-Healing grant
- ERC Consolidator ('STEMMING FROM NERVE') [647844]
- ERC Synergy ('KILL OR DIFFERENTIATE') [856529]
- Austrian Science Fund (FWF)
- EMBO Young Investigator grants
- Russian Science Foundation [N19-14-00260, 16-15-10273, 19-15-00241]
- Ministry of Science and Higher Education of the Russian Federation [075-15-2020-784]
- Austrian Science Fund [DOC 33-B27]
- Novo Nordisk Foundation (Postdoctoral Fellowship in Endocrinology and Metabolism at International Elite Environments) [NNF17OC0026874]
- Stiftelsen Riksbankens Jubileumsfond (Erik Ronnbergs fond)
- Swedish Research Council
- Swedish Childhood Cancer Fund
- Swedish Foundation for Strategic Research
- Knut and Alice Wallenberg Foundation, National Bioinformatics Infrastructure Sweden at SciLifeLab
- Lise Meitner Programme
- StratNeuro SRP Postdoctoral Research 2020-2021 [C333740002]
- Karolinska Institutet (KI Foundations)
- Karolinska Institutet (Career Development grant)
- Karolinska Institutet (PhD student KID funding)
- Karolinska Institutet (SFO StratNeuro funding)
- Karolinska Institutet (Center of Innovative Medicine)
- Ollie and Elof Ericssons Foundation
- Tornspiran Foundation
- Jeanssons Foundation
- Sven and Ebba-Christina Hagbergs prize and research grant
- Knut and Alice Wallenberg project grant
- Fredrik and Ingrid Thurings Foundation
- Childhood Cancer Foundation (Barncancerfonden)
- Ahlen Foundation
- Ake Wibergs Foundation
- Tore Nilssons Foundation
- Swedish Foundations starting grant
- Erling Person Foundation
- DFG [RA 2889/1-1]
- NIH (NHLBI) [1R01HL131768]
- NSF [CAREER 1452964]
- Russian Science Foundation [16-15-10273, 19-15-00241] Funding Source: Russian Science Foundation
- European Research Council (ERC) [856529, 647844] Funding Source: European Research Council (ERC)
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Single-cell transcriptome profiling of human embryonic sympathoadrenal tissues reveals developmental transitions and suggests that intra-adrenal sympathoblasts from Schwann cell precursors may be potential neuroblastoma cell origins. The majority of extra-adrenal sympathoblasts appear to arise from migratory neural crest cells, while intra-adrenal sympathoblasts seem to be directly derived from nerve-associated Schwann cell precursors. This process persists during several weeks of development within the large intra-adrenal ganglia-like structures, potentially serving as reservoirs of originating cells in neuroblastoma.
Single-cell transcriptome profiling of human embryonic sympathoadrenal tissues identifies developmental transitions and suggests that intra-adrenal sympathoblasts arising from Schwann cell precursors are a potential neuroblastoma cell of origin. Characterization of the progression of cellular states during human embryogenesis can provide insights into the origin of pediatric diseases. We examined the transcriptional states of neural crest- and mesoderm-derived lineages differentiating into adrenal glands, kidneys, endothelium and hematopoietic tissue between post-conception weeks 6 and 14 of human development. Our results reveal transitions connecting the intermediate mesoderm and progenitors of organ primordia, the hematopoietic system and endothelial subtypes. Unexpectedly, by using a combination of single-cell transcriptomics and lineage tracing, we found that intra-adrenal sympathoblasts at that stage are directly derived from nerve-associated Schwann cell precursors, similarly to local chromaffin cells, whereas the majority of extra-adrenal sympathoblasts arise from the migratory neural crest. In humans, this process persists during several weeks of development within the large intra-adrenal ganglia-like structures, which may also serve as reservoirs of originating cells in neuroblastoma.
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