Single-cell mapping of progressive fetal-to-adult transition in human hematopoiesis [HSPCs single-cell RNAseq]

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. Naïve CD4 and CD8 T cells, and CD34+ hematopoietic stem and progenitor cells (HSPCs) were isolated from human samples of three different groups: Fetal (18-23 gestational weeks), full-term newborn (37+ gestational weeks at birth), and adults age 23 to 53. For each group, five independent donors were analyzed, but not all cell types could be sequenced for every patient. Single-cell RNAseq of FACSorted hematopoietic stem and progenitor cells (HSPCs; CD34+CD45mid) from human samples: Fetal (18-23 gestational weeks) bone marrow, full-term newborn (37+ gestational weeks at birth) umbilical cord blood, and adult (ages 23 to 53) bone marrow. CD4 and CD8 naive T cells were also sorted from these same donors for RNAseq. Analysis code: https://github.com/dtm2451/ProgressiveHematopoiesis Figures: https://figshare.com/projects/Single-cell_mapping_of_progressive_fetal-to-adult_transition_in_human_naive_T_cells/76143 >>>Raw data are not available due to patient privacy concerns<<<