Dynamics of HSPC repopulation in nonhuman primates revealed by a decade-long clonal-tracking study

Sanggu Kim; Namshin Kim; Angela P Presson; Mark E Metzger; Aylin C Bonifacino; Mary Sehl; Samson A Chow; Gay M Crooks; Cynthia E Dunbar; Dong Sung An; Robert E Donahue; Irvin S Y Chen

doi:10.1016/j.stem.2013.12.012

Dynamics of HSPC repopulation in nonhuman primates revealed by a decade-long clonal-tracking study

Cell Stem Cell. 2014 Apr 3;14(4):473-85. doi: 10.1016/j.stem.2013.12.012.

Authors

Affiliations

¹ 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.
² Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, 111 Gwahangno, Yuseong-gu, Daejeon 305-806, Korea.
³ 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.
⁴ Hematology Branch, National Heart, Lung and Blood Institute, NIH, Rockville, MD 20850, USA.
⁵ 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.
⁶ 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.
⁷ Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁸ 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.
⁹ 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: [email protected].

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation*
Cell Lineage*
Cell Tracking*
Cells, Cultured
Genetic Vectors
Hematopoietic Stem Cells / cytology*
Hematopoietic Stem Cells / metabolism
Lymphocytes / cytology*
Lymphocytes / metabolism
Macaca mulatta
Mice
Myeloid Cells / cytology*
Myeloid Cells / metabolism
RNA, Small Interfering / genetics
Receptors, CCR5 / chemistry
Receptors, CCR5 / genetics
Receptors, CCR5 / metabolism
Transgenes / physiology

Substances

RNA, Small Interfering
Receptors, CCR5

Abstract

Publication types

MeSH terms

Substances

Grants and funding