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In Vivo Tracking of Human Hematopoiesis Reveals Patterns of Clonal Dynamics during Early and Steady-State Reconstitution Phases

Biasco, L; Pellin, D; Scala, S; Dionisio, F; Basso-Ricci, L; Leonardelli, L; Scaramuzza, S; ... Aiuti, A; + view all (2016) In Vivo Tracking of Human Hematopoiesis Reveals Patterns of Clonal Dynamics during Early and Steady-State Reconstitution Phases. Cell Stem Cell , 19 (1) pp. 107-119. 10.1016/j.stem.2016.04.016. Green open access

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Abstract

Hematopoietic stem/progenitor cells (HSPCs) are capable of supporting the lifelong production of blood cells exerting a wide spectrum of functions. Lentiviral vector HSPC gene therapy generates a human hematopoietic system stably marked at the clonal level by vector integration sites (ISs). Using IS analysis, we longitudinally tracked >89,000 clones from 15 distinct bone marrow and peripheral blood lineages purified up to 4 years after transplant in four Wiskott-Aldrich syndrome patients treated with HSPC gene therapy. We measured at the clonal level repopulating waves, populations' sizes and dynamics, activity of distinct HSPC subtypes, contribution of various progenitor classes during the early and late post-transplant phases, and hierarchical relationships among lineages. We discovered that in-vitro-manipulated HSPCs retain the ability to return to latency after transplant and can be physiologically reactivated, sustaining a stable hematopoietic output. This study constitutes in vivo comprehensive tracking in humans of hematopoietic clonal dynamics during the early and late post-transplant phases.

Type: Article
Title: In Vivo Tracking of Human Hematopoiesis Reveals Patterns of Clonal Dynamics during Early and Steady-State Reconstitution Phases
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.stem.2016.04.016
Publisher version: http://dx.doi.org/10.1016/j.stem.2016.04.016
Language: English
Additional information: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Keywords: Science & Technology, Life Sciences & Biomedicine, Cell & Tissue Engineering, Cell Biology, Wiskott-Aldrich-Syndrome, Stem-Cell Transplantation, Myeloid-Based Model, Human Cord Blood, Gene-Therapy, Lentiviral Vector, Scid Patients, Bone-Marrow, Progenitors, Immunodeficiency
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
URI: https://discovery.ucl.ac.uk/id/eprint/1506123
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