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Single-Cell Mapping of Progressive Fetal-to-Adult Transition in Human Naive T Cells
Daniel G Bunis1, Yelena Bronevetsky2, Elisabeth Krow-Lucal2
1Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA.
The human immune system develops continuously from fetus to adult, not in discrete stages. This research clarifies immune system maturation, impacting newborn infection prevention and cord blood transplantation strategies.
Area of Science:
- Immunology
- Developmental Biology
- Hematopoiesis
Background:
- The human immune system transitions from fetal tolerance to adult anti-pathogen responses post-natally.
- Previous models suggested discrete waves of immune cell development, but human evidence was inconclusive.
Purpose of the Study:
- To investigate the developmental trajectory of the human immune system from fetal to adult stages.
- To clarify whether immune cell maturation occurs as a continuum or through discrete ontological layers.
Main Methods:
- Combined bulk and single-cell transcriptional profiling.
- Analyzed lymphoid cells, myeloid cells, and hematopoietic stem-progenitor cells (HSPCs).
- Compared samples across fetal, perinatal, and adult developmental stages.
Main Results:
- Demonstrated a progressive maturation continuum rather than discrete developmental waves.
- Observed significant inter-individual variation in immune cell maturity at birth.
- Provided evidence against a discrete ontological layer model for adult immune cells.
Conclusions:
- The fetal-to-adult immune system transition is a gradual process with considerable variation.
- Findings inform strategies for neonatal infection prophylaxis.
- Implications for the clinical use of umbilical cord blood (UCB) in transplantation.
