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Cell Stem Cell. 2016 Dec 1;19(6):768-783. doi: 10.1016/j.stem.2016.08.013. Epub 2016 Sep 22.

A Transient Developmental Hematopoietic Stem Cell Gives Rise to Innate-like B and T Cells.

Author information

1
Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
2
Eli and Edythe Broad Center of Regeneration Medicine and Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
3
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.

Abstract

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.

KEYWORDS:

development; hematopoiesis; hematopoietic stem cell; immune cells; innate-like B and T lymphocytes; lineage potential; lineage tracing; self-renewal; tissue resident; transplantation

PMID:
27666010
PMCID:
PMC5524382
DOI:
10.1016/j.stem.2016.08.013
[Indexed for MEDLINE]
Free PMC Article

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