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, myeloid, 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 interindividual variation at the time of birth — rather than via a transition between discrete waves. These findings have important implications in 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.
Bunis, Daniel and Bronevetsky, Yelena and Krow-Lucal, Elisabeth and Bhakta, Nirav R. and Kim, Charles C. and Nerella, Srilaxmi and Jones, Norman and Mendoza, Ventura F. and Bryson, Yvonne J. and Gern, James E. and Rutishauser, Rachel L. and Ye, Chun Jimmie and Sirota, Marina and McCune, Joseph M. and Burt, Trevor D., Single-Cell Mapping of Progressive Fetal-to-Adult Transition in Human Hematopoiesis. Available at SSRN: https://ssrn.com/abstract=3569532 or http://dx.doi.org/10.2139/ssrn.3569532
This version of the paper has not been formally peer reviewed.
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