Single-Cell Mapping of Progressive Fetal-to-Adult Transition in Human Naive T Cells

Daniel G Bunis; Yelena Bronevetsky; Elisabeth Krow-Lucal; Nirav R Bhakta; Charles C Kim; Srilaxmi Nerella; Norman Jones; Ventura F Mendoza; Yvonne J Bryson; James E Gern; Rachel L Rutishauser; Chun Jimmie Ye; Marina Sirota; Joseph M McCune; Trevor D Burt

doi:10.1016/j.celrep.2020.108573

Single-Cell Mapping of Progressive Fetal-to-Adult Transition in Human Naive T Cells

Cell Rep. 2021 Jan 5;34(1):108573. doi: 10.1016/j.celrep.2020.108573.

Authors

Affiliations

¹ Eli 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.
² Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
³ Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
⁴ Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA; Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
⁵ Division of Pediatric Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine at UCLA, Mattel Children's Hospital UCLA, Los Angeles, CA, USA.
⁶ Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
⁷ Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA; Division of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA.
⁸ Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA; Department of Pediatrics, Division of Neonatology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: marina.sirota@ucsf.edu.
⁹ Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. Electronic address: mike.mccune@gatesfoundation.org.
¹⁰ Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA; Department of Pediatrics, Division of Neonatology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: trevor.burt@duke.edu.

Abstract

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.

Keywords: developmental stage score; hematopoietic ontogeny; hematopoietic stem and progenitor cells; hematopoietic stem cells; human immune development; monocytes; naive T cells; newborn immune development; scRNA-seq; single-cell RNA sequencing.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Bone Marrow / metabolism
Cell Culture Techniques
Female
Fetal Blood
Fetus / metabolism*
Hematopoietic Stem Cells / metabolism*
Humans
Immunity
Lymphocytes / metabolism*
Myeloid Cells / metabolism*
Pregnancy
Sequence Analysis, RNA
Single-Cell Analysis*
T-Lymphocytes / metabolism*
Transcriptome*

Abstract

Publication types

MeSH terms

Grants and funding