Complexity and tumor potential of human embryonic sympatho-adrenal area including neural crest and mesodermal derivatives

We addressed heterogeneity of neural crest- and mesoderm-derived lineages developing into adrenal glands, kidneys, endothelium and hematopoietic tissue for understanding transitions, integration and tumor-initiating states between week 6 and 14 of human development. We identified new transitions connecting intermediate mesoderm and progenitors of organ primordia, hematopoietic system and endothelial subtypes. Unexpectedly, we revealed that in humans, contrary to mice, nerve-associated Schwann cell precursors give rise to highly-proliferative sympathoblasts within adrenal gland, which in turn could transit into neuroendocrine chromaffin cells. The analysis of cell state signatures in relation to survival curves of patients suggested Schwann cell precursor-derived sympathoadrenal subtypes as origin for different neuroblastoma tumors. Overall design: We isolated individual cells from dissected intact adrenal glands with surrounding tissue from human embryos at post-conception weeks 6, 8, 9, 11, 12, 14 and subjected them to single cell transcriptomics sequencing using 10x Chromium approach.