Deciphering the transcriptional landscape of human pluripotent stem cell-derived GnRH neurons: the role of Wnt signaling in patterning the neural fate.
Yafei WangShrinidhi MadhusudanLudovica CotellessaJouni KvistNazli EskiciVenkatram YellapragadaKristiina PulliCarina LundKirsi VaaralahtiTimo TuuriPaolo GiacobiniTaneli RaivioPublished in: Stem cells (Dayton, Ohio) (2022)
Hypothalamic gonadotropin-releasing hormone (GnRH) neurons lay the foundation for human development and reproduction, however, the critical cell populations and the entangled mechanisms underlying the development of human GnRH neurons remain poorly understood. Here, by utilizing our established human pluripotent stem cells-derived GnRH neuron model, we decoded the cellular heterogeneity and differentiation trajectories at the single-cell level. We found that a glutamatergic neuron population, which generated together with GnRH neurons, showed similar transcriptomic properties with olfactory sensory neuron and provided the migratory path for GnRH neurons. Through trajectory analysis, we identified a specific gene module activated along the GnRH neuron differentiation lineage, and we examined one of the transcription factors, DLX5, expression in human fetal GnRH neurons. Furthermore, we found that Wnt inhibition could increase DLX5 expression, and improve the GnRH neuron differentiation efficiency through promoting neurogenesis and switching the differentiation fates of neural progenitors into glutamatergic neurons/GnRH neurons. Our research comprehensively reveals the dynamic cell population transition and gene regulatory network during GnRH neuron differentiation.
Keyphrases
- single cell
- pluripotent stem cells
- endothelial cells
- spinal cord
- induced pluripotent stem cells
- rna seq
- transcription factor
- poor prognosis
- stem cells
- gene expression
- depressive symptoms
- oxidative stress
- high throughput
- dna methylation
- cell proliferation
- cell therapy
- spinal cord injury
- bone marrow
- brain injury
- blood brain barrier
- genetic diversity
- dna binding
- mesenchymal stem cells