title: Transplantation Dose Alters the Differentiation Program of Hematopoietic Stem Cells.
abstract: Hematopoietic stem cell (HSC) transplantation is the most prevalent stem cell therapy, but it remains a risky procedure. To improve this treatment, it is important to understand how transplanted stem cells rebuild the blood and immune systems and how this process is impacted by transplantation variables such as the HSC dose. Here, we find that, in the long term following transplantation, 70%-80% of donor-HSC-derived clones do not produce all measured blood cell types. High HSC doses lead to more clones that exhibit balanced lymphocyte production, whereas low doses produce more T-cell-specialized clones. High HSC doses also produce significantly higher proportions of early-differentiating clones compared to low doses. These complex differentiation behaviors uncover the clonal-level regeneration dynamics of hematopoietic regeneration and suggest that transplantation dose can be exploited to improve stem cell therapy.
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Casey
authors.initials: C
authors.lastname: Brewer
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Chu
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Chin
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: ronglu@usc.edu.
authors.forename: Rong
authors.initials: R
authors.lastname: Lu
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000166:cytology; D002452:Cell Count; D002454:Cell Differentiation; D019070:Cell Lineage; D002999:Clone Cells; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology; D008810:Mice, Inbred C57BL; D013997:Time Factors