Leg ulcers are a major complication of sickle cell disease (SCD) that can cause severe complications. They are particularly challenging to treat and therapeutic innovation is needed. We previously showed that SCD ulcers display a delayed wound healing due to decreased angiogenesis. During pregnancy, fetal microchimeric cells (FMC) transferred to the mothers are recruited to maternal wounds and improve angiogenesis. After delivery, FMC persist in maternal bone marrow for decades. Here, we questioned whether fetal cells could also improve SCD ulcers in the post-partum setting. We found that skin healing was similarly improved in post-partum mice and in pregnant mice, through increased proliferation and angiogenesis. In a SCD mouse model that recapitulates SCD refractory ulcers, we showed that post-partum SCD mice healed more quickly as compared to virgin ones. This was associated with the recruitment of fetal cells in maternal wounds where they harbored markers of leukocytes and endothelial cells. In a retrospective cohort of SCD patients, we demonstrated using several parameters that ever parous SCD women had a decreased burden related to leg ulcers compared to nulliparous women. Taken together, these results indicate that healing capacities of FMC are maintained long after delivery and may be targeted to promote wound healing in post-partum SCD patients.

Neural crest cells exemplify cellular diversification from a multipotent progenitor population. However, the full sequence of molecular choices orchestrating the emergence of neural crest heterogeneity from the embryonic ectoderm remains elusive. Gene-regulatory-networks (GRN) govern early development and cell specification towards definitive neural crest. Here, we combine ultra-dense single cell transcriptomes with machine-learning and large-scale experimental validation to provide a comprehensive GRN underlying neural crest fate diversification from induction to early migration stages. During gastrulation, a transient neural border zone state precedes choice between neural crest and placodes following a "dual convergence model". Transcription factor connectome and bifurcation analyses demonstrate the early emergence of neural crest fates at neural plate stage, alongside an unbiased multipotent lineage persisting until after epithelial-mesenchymal transition. We decipher the circuits driving cranial and vagal neural crest formation and provide a broadly applicable strategy for investigating SC transcriptomes in vertebrate GRNs in development, evolution and disease.