A Transient Developmental Hematopoietic Stem Cell Gives Rise to Innate-like B and T Cells.
The generation of distinct hematopoietic cell types, including tissue-resident immune cells, distinguishes fetal from adult hematopoiesis. However, the mechanisms underlying differential cell production to generate a layered immune system during hematopoietic development are unclear. Using an irreversible lineage-tracing model, we identify a definitive hematopoietic stem cell (HSC) that supports long-term multilineage reconstitution upon transplantation into adult recipients but does not persist into adulthood in situ. These HSCs are fully multipotent, yet they display both higher lymphoid cell production and greater capacity to generate innate-like B and T lymphocytes as compared to coexisting fetal HSCs and adult HSCs. Thus, these developmentally restricted HSCs (drHSCs) define the origin and generation of early lymphoid cells that play essential roles in establishing self-recognition and tolerance, with important implications for understanding autoimmune disease, allergy, and rejection of transplanted organs.
Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Anna E
AE
Beaudin
Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Scott W
SW
Boyer
Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Jessica
J
Perez-Cunningham
Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Gloria E
GE
Hernandez
Eli and Edythe Broad Center of Regeneration Medicine and Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
S Christopher
SC
Derderian
Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Chethan
C
Jujjavarapu
Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Eric
E
Aaserude
Eli and Edythe Broad Center of Regeneration Medicine and Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Tippi
T
MacKenzie
Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA. Electronic address: cforsber@ucsc.edu.
E Camilla
EC
Forsberg
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D019070:Cell Lineage; D060833:Cellular Microenvironment; D016922:Cellular Senescence; D047109:Fetal Development; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D007113:Immunity, Innate; D008099:Liver / Q000166:cytology / Q000196:embryology; D051379:Mice; D017423:Sequence Analysis, RNA; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
D049452:Green Fluorescent Proteins
development; hematopoiesis; hematopoietic stem cell; immune cells; innate-like B and T lymphocytes; lineage potential; lineage tracing; self-renewal; tissue resident; transplantation
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