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Clonal analysis of thymus-repopulating cells presents direct evidence for self-renewal division of human hematopoietic stem cells.
Blood. 2006 Oct 01; 108(7):2446-54.Blood

Abstract

To elucidate the in vivo kinetics of human hematopoietic stem cells (HSCs), CD34+CD38- cells were infected with lentivirus vector and transplanted into immunodeficient mice. We analyzed the multilineage differentiation and self-renewal abilities of individual thymus-repopulating clones in primary recipients, and their descending clones in paired secondary recipients, by tracing lentivirus gene integration sites in each lymphomyeloid progeny using a linear amplification-mediated polymerase chain reaction (PCR) strategy. Our clonal analysis revealed that a single human thymus-repopulating cell had the ability to produce lymphoid and myeloid lineage cells in the primary recipient and each secondary recipient, indicating that individual human HSCs expand clonally by self-renewal division. Furthermore, we found that the proportion of HSC clones present in the CD34+ cell population decreased as HSCs replicated during extensive repopulation and also as the differentiation capacity of the HSC clones became limited. This indicates the restriction of the ability of individual HSCs despite the expansion of total HSC population. We also demonstrated that the extensive self-renewal potential was confined in the relatively small proportion of HSC clones. We conclude that our clonal tracking studies clearly demonstrated that heterogeneity in the self-renewal capacity of HSC clones underlies the differences in clonal longevity in the CD34+ stem cell pool.

Authors+Show Affiliations

Division of Hematopoiesis, Research Center for Regenerative Medicine, Tokai University School of Medicine, Isehara, Kanagawa.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16757689

Citation

Yahata, Takashi, et al. "Clonal Analysis of Thymus-repopulating Cells Presents Direct Evidence for Self-renewal Division of Human Hematopoietic Stem Cells." Blood, vol. 108, no. 7, 2006, pp. 2446-54.
Yahata T, Yumino S, Seng Y, et al. Clonal analysis of thymus-repopulating cells presents direct evidence for self-renewal division of human hematopoietic stem cells. Blood. 2006;108(7):2446-54.
Yahata, T., Yumino, S., Seng, Y., Miyatake, H., Uno, T., Muguruma, Y., Ito, M., Miyoshi, H., Kato, S., Hotta, T., & Ando, K. (2006). Clonal analysis of thymus-repopulating cells presents direct evidence for self-renewal division of human hematopoietic stem cells. Blood, 108(7), 2446-54.
Yahata T, et al. Clonal Analysis of Thymus-repopulating Cells Presents Direct Evidence for Self-renewal Division of Human Hematopoietic Stem Cells. Blood. 2006 Oct 1;108(7):2446-54. PubMed PMID: 16757689.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clonal analysis of thymus-repopulating cells presents direct evidence for self-renewal division of human hematopoietic stem cells. AU - Yahata,Takashi, AU - Yumino,Shizu, AU - Seng,Yin, AU - Miyatake,Hiroko, AU - Uno,Tomoko, AU - Muguruma,Yukari, AU - Ito,Mamoru, AU - Miyoshi,Hiroyuki, AU - Kato,Shunichi, AU - Hotta,Tomomitsu, AU - Ando,Kiyoshi, Y1 - 2006/06/06/ PY - 2006/6/8/pubmed PY - 2006/10/25/medline PY - 2006/6/8/entrez SP - 2446 EP - 54 JF - Blood JO - Blood VL - 108 IS - 7 N2 - To elucidate the in vivo kinetics of human hematopoietic stem cells (HSCs), CD34+CD38- cells were infected with lentivirus vector and transplanted into immunodeficient mice. We analyzed the multilineage differentiation and self-renewal abilities of individual thymus-repopulating clones in primary recipients, and their descending clones in paired secondary recipients, by tracing lentivirus gene integration sites in each lymphomyeloid progeny using a linear amplification-mediated polymerase chain reaction (PCR) strategy. Our clonal analysis revealed that a single human thymus-repopulating cell had the ability to produce lymphoid and myeloid lineage cells in the primary recipient and each secondary recipient, indicating that individual human HSCs expand clonally by self-renewal division. Furthermore, we found that the proportion of HSC clones present in the CD34+ cell population decreased as HSCs replicated during extensive repopulation and also as the differentiation capacity of the HSC clones became limited. This indicates the restriction of the ability of individual HSCs despite the expansion of total HSC population. We also demonstrated that the extensive self-renewal potential was confined in the relatively small proportion of HSC clones. We conclude that our clonal tracking studies clearly demonstrated that heterogeneity in the self-renewal capacity of HSC clones underlies the differences in clonal longevity in the CD34+ stem cell pool. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/16757689/Clonal_analysis_of_thymus_repopulating_cells_presents_direct_evidence_for_self_renewal_division_of_human_hematopoietic_stem_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-4971(20)52531-7 DB - PRIME DP - Unbound Medicine ER -