期刊
CELL STEM CELL
卷 19, 期 6, 页码 768-783出版社
CELL PRESS
DOI: 10.1016/j.stem.2016.08.013
关键词
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资金
- NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01DK100917]
- Alex's Lemonade Stand Foundation Innovation Award
- American Asthma Foundation Research Scholar award
- NIH [2T32GM008646]
- HHMI Gilliam Fellow Award
- California Institute for Regenerative Medicine (CIRM) Training grant [TG2-01157]
- CIRM [CL1-00506, FA1-00617-1]
- CIRM New Faculty Award [RN1-00540]
- American Cancer Society Research Scholar Award [RSG-13-193-01-DDC]
- NHLBI Mentored Career Development Award [K01HL130753]
- CIRM New Faculty Physician Scientist Translational Research Award [RN3-06532]
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.
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