In Vivo Tracking of Human Hematopoiesis Reveals Patterns of Clonal Dynamics during Early and Steady-State Reconstitution Phases
نویسندگان
چکیده
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.
منابع مشابه
Focal Adhesion Kinase (FAK) Involvement in Human Endometrial Remodeling During the Menstrual Cycle
Background: Endometrial remodeling occurs during each menstrual cycle in women. Reports have shown that, in a variety of cell types, processes such as proliferation, signaling complex formation and extra cellular matrix remodeling require a cytoplasmic tyrosine kinase, focal adhesion kinase (FAK). The present study has focused on the expression pattern of FAK in human endometrium during the men...
متن کاملUnperturbed vs. post-transplantation hematopoiesis: both in vivo but different
PURPOSE OF REVIEW Hematopoietic stem cell (HSC) transplantation has yielded tremendous information on experimental properties of HSCs. Yet, it remains unclear whether transplantation reflects the physiology of hematopoiesis. A limitation is the difficulty in accessing HSC functions without isolation, in-vitro manipulation and readout for potential. New genetic fate mapping and clonal marking te...
متن کاملQuaternion-based Finite-time Sliding Mode Controller Design for Attitude Tracking of a Rigid Spacecraft during High-thrust Orbital Maneuver in the Presence of Disturbance Torques
In this paper, a quaternion-based finite-time sliding mode attitude controller is designed for a spacecraft performing high-thrust orbital maneuvers, with cold gas thrusters as its actuators. The proposed controller results are compared with those of a quaternion feedback controller developed for the linearized spacecraft dynamics, in terms of settling time, steady-state error, number of thrust...
متن کاملIn vivo cellular imaging pinpoints the role of reactive oxygen species in the early steps of adult hematopoietic reconstitution.
Few techniques are available to characterize in vivo the early cellular dynamics of long-term reconstitution of hematopoiesis after transplantation of hematopoietic stem cells (HSCs) after lethal irradiation. Using a fiber-optic imaging system, we track the early steps of in vivo recruitment and proliferation of Lin(-)Sca-1(+)c-Kit(+)CD34(-) (LSKCD34(-)) HSCs highly enriched in HSCs and transpl...
متن کاملHEMATOPOIESIS AND STEM CELLS Analysis of the clonal growth and differentiation dynamics of primitive barcoded human cord blood cells in NSG mice
Hematopoiesis is a complex, hierarchically ordered, multistep process that originates in cells with latent differentiation potentialities that can be maintained through many divisions. The features of this process have been inferred largely from studies of the in vitro or in vivo growth and differentiation properties of cells with distinct phenotypes. Additional contributions to our understandi...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 19 شماره
صفحات -
تاریخ انتشار 2016