Summary

Whereas the human fetal immune system is poised to generate immune tolerance and suppress inflammation in utero, an adult-like immune system emerges to orchestrate anti-pathogen immune responses in post-natal life. It has been posited that cells of the adult immune system arise as a discrete ontological "layer" of hematopoietic stem-progenitor cells (HSPCs) and their progeny; evidence supporting this model in humans has, however, been inconclusive. Here, we combine bulk and single-cell transcriptional profiling of lymphoid cells, myeloid cells, and HSPCs from fetal, perinatal, and adult developmental stages to demonstrate that the fetal-to-adult transition occurs progressively along a continuum of maturity-with a substantial degree of inter-individual variation at the time of birth-rather than via a transition between discrete waves. These findings have important implications for the design of strategies for prophylaxis against infection in the newborn and for the use of umbilical cord blood (UCB) in the setting of transplantation.

Overall design

Single-cell RNAseq of FACSorted naïve CD4 (CD4+CD45RA+CD27+CD25-) and CD8 (+CD45RA+CD27+CCR7+CD95-) T cells from human samples: Fetal (18-23 gestational weeks) spleen, full-term newborn (37+ gestational weeks at birth) umbilical cord blood, and adult (ages 23 to 53) peripheral blood. CD34+ HSPCs were also sorted from these same donors for single-cell RNAseq.

Contributors

Daniel G Bunis 1, Yelena Bronevetsky 2, Elisabeth Krow-Lucal 2, Nirav R Bhakta 3, Charles C Kim 2, Srilaxmi Nerella 3, Norman Jones 4, Ventura F Mendoza 4, Yvonne J Bryson 5, James E Gern 6, Rachel L Rutishauser 2, Chun Jimmie Ye 7, Marina Sirota 8, Joseph M McCune 9, Trevor D Burt 10

Contact

trevor.burt@duke.edu.(Trevor D Burt)