Spatiotemporal structure of cell fate decisions in murine neural crest

Abstract

Neural crest cells are embryonic progenitors that generate numerous cell types in vertebrates. With single-cell analysis, we show that mouse trunk neural crest cells become biased toward neuronal lineages when they delaminate from the neural tube, whereas cranial neural crest cells acquire ectomesenchyme potential dependent on activation of the transcription factor Twist1. The choices that neural crest cells make to become sensory, glial, autonomic, or mesenchymal cells can be formalized as a series of sequential binary decisions. Each branch of the decision tree involves initial coactivation of bipotential properties followed by gradual shifts toward commitment. Competing fate programs are coactivated before cells acquire fate-specific phenotypic traits. Determination of a specific fate is achieved by increased synchronization of relevant programs and concurrent repression of competing fate programs.

Single‐cell study of neural stem cells derived from human iPSCs reveals distinct progenitor populations with neurogenic and gliogenic potential

“…Our hypothesis relies on the developmental model concept that NES cells accurately represent a model of the developing neural ectoderm. In a recently published high impact study, we noted results describing neural tube and neural crest/glia cell identity during development by displaying Draxin + cells located in the neural tube region and Slc1a3 + cells located in the peripheral and outside region of the neural tube as glia progenitors/neural crest cells in mouse E9.5 developing spinal cord (Figure 1d; Soldatov et al, 2019).…”

“…(c) Barplot of percentage of AF22 NES cells in each of 4 clusters. (d) DRAXIN green (Neural tube) SLC1A3 red, in situ RNAScope E9.5 mouse developing spinal cord, from figure S2f Soldatov et al (). (e) Heat map of genes enriched in cell clusters, highlighting neurogenic progenitor clustering division, selected by fold change…”

Adult tissue–derived neural crest-like stem cells: Sources, regulatory networks, and translational potential

“…The recent expansion of molecular biological techniques including single‐cell RNA‐seq, ChIP‐seq, and ATAC‐seq have facilitated the dissection of the genetic program controlling NC development. These genomic approaches have provided important insights into gene regulatory mechanisms and uncovered new regulatory factors involved in control of NC formation and diversification . It is now clear that an intricate array of transcription factors and signaling molecules act in concert to imbue NC cells with its broad multipotency and migratory ability.…”

“…The NC GRN itself can be envisioned as a series of sequential binary decisions leading to differentiation into derivative fates. Recently Twist1 has been reported to play a critical role as a regulator of NC fate decision, and it biases NC commitment toward a mesenchymal fate . Conversely, FoxD3 represses the mesenchymal program of delaminating NCs .…”

“…Recently Twist1 has been reported to play a critical role as a regulator of NC fate decision, and it biases NC commitment toward a mesenchymal fate. 45 Conversely, FoxD3 represses the mesenchymal program of delaminating NCs. 48 Hirschsprung disease.…”