Details

Autor(en) / Beteiligte

• Biasco, Luca
• Pellin, Danilo
• Scala, Serena
• Dionisio, Francesca
• Basso-Ricci, Luca
• Leonardelli, Lorena
• Scaramuzza, Samantha
• Baricordi, Cristina
• Ferrua, Francesca
• Cicalese, Maria Pia
• Giannelli, Stefania
• Neduva, Victor
• Dow, David J.
• Schmidt, Manfred
• Von Kalle, Christof
• Roncarolo, Maria Grazia
• Ciceri, Fabio
• Vicard, Paola
• Wit, Ernst
• Di Serio, Clelia
• Naldini, Luigi
• Aiuti, Alessandro

Titel

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

Ist Teil von

• Cell stem cell, 2016-07, Vol.19 (1), p.107-119

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Hematopoietic reconstitution occurs in two distinct clonal waves•A few thousand HSPC clones stably sustain multilineage blood cell production•Steady-state hematopoiesis after transplant is maintained by both HSCs and MPPs•Natural killer clones have closer relationships to myeloid cells than to lymphoid cells Biasco et al. report a clonal tracking study on the dynamics and nature of hematopoietic reconstitution in humans after transplant. Using integration sites as molecular tags, they measured, in gene therapy patients, repopulating waves, population size and dynamics, activity of progenitor subtypes during the early and late post-transplant phases, and hierarchical relationships among lineages.