Dynamics of HSPC repopulation in nonhuman primates revealed by a decade-long clonal-tracking study.
In mice, clonal tracking of hematopoietic stem cells (HSCs) has revealed variations in repopulation characteristics. However, it is unclear whether similar properties apply in primates. Here, we examined this issue through tracking of thousands of hematopoietic stem and progenitor cells (HSPCs) in rhesus macaques for up to 12 years. Approximately half of the clones analyzed contributed to long-term repopulation (over 3-10 years), arising in sequential groups and likely representing self-renewing HSCs. The remainder contributed primarily for the first year. The long-lived clones could be further subdivided into functional groups contributing primarily to myeloid, lymphoid, or both myeloid and lymphoid lineages. Over time, the 4%-10% of clones with robust dual lineage contribution predominated in repopulation. HSPCs expressing a CCR5 shRNA transgene behaved similarly to controls. Our study therefore documents HSPC behavior in a clinically relevant model over a long time frame and provides a substantial system-level data set that is a reference point for future work.
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; UCLA AIDS Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Sanggu
S
Kim
Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, 111 Gwahangno, Yuseong-gu, Daejeon 305-806, Korea.
Namshin
N
Kim
Department of Biostatistics, University of California, Los Angeles, Los Angeles, CA 90095, USA; UCLA AIDS Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Angela P
AP
Presson
Hematology Branch, National Heart, Lung and Blood Institute, NIH, Rockville, MD 20850, USA.
Mark E
ME
Metzger
Hematology Branch, National Heart, Lung and Blood Institute, NIH, Rockville, MD 20850, USA.
Aylin C
AC
Bonifacino
Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Biomathematics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Mary
M
Sehl
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA; UCLA AIDS Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Samson A
SA
Chow
Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Gay M
GM
Crooks
Hematology Branch, National Heart, Lung and Blood Institute, NIH, Rockville, MD 20850, USA.
Cynthia E
CE
Dunbar
UCLA AIDS Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; School of Nursing, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Dong Sung
DS
An
Hematology Branch, National Heart, Lung and Blood Institute, NIH, Rockville, MD 20850, USA.
Robert E
RE
Donahue
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; UCLA AIDS Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: syuchen@mednet.ucla.edu.
Irvin S Y
IS
Chen
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D058948:Cell Tracking; D002478:Cells, Cultured; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism; D008253:Macaca mulatta; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D019713:Receptors, CCR5 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019076:Transgenes / Q000502:physiology
D034741:RNA, Small Interfering; D019713:Receptors, CCR5