Single Cell Phenotyping Reveals Heterogeneity Among Hematopoietic Stem Cells Following Infection.

Maia A. Smith, Juliane Liepe, Aaron Sim, Reema Khorshed, Narges M. Rashidi, Nico Scherf, Axel Krinner, Ingo Roeder, Cristina Lo Celso, Michael P. H. Stumpf.

Stem Cells 2017;35:2292-2304.

Speaker: Eduardo A. Isasi Diaz (伊彥德)                     Time: 15:10-16:00, Jan. 3, 2017                     

Commentator: Professor Wen-Tai Chiu (邱文泰教授)   Place: Room 601                                         

Abstract

The hematopoietic stem cells (HSC) niche provides essential indications for the microenvironmental production and maintenance of HSCs within the bone marrow. During immune responses resulting from infection, the dynamics of the HSC is disturbed but is not known whether these changes are caused by HSC-niche interaction. Researchers visualize HSCs directly in vivo, enabling detailed analysis of the 3D niche dynamic and migration patterns in murine bone marrow after infection. Spatial statistical analysis of these HSC trajectories reveals two distinct modes of HSC behavior: a patter of revisiting previously explored space and a pattern of exploring new spaces. Whereas HSCs from control donors predominantly follow the first pattern, those from infected mice adopt both strategies.

It has been shown that chronic infection profoundly affects hematopoiesis by exhausting stem cell function, but these changes have not yet been resolved at the single cell level. In this investigation, the stem cell niche interactions triggered by infection are heterogeneous whereby cells exhibit different behavioral patterns (movement highly restricted or exploration of much larger regions of space over time). Overall, cells from infected mice display higher levels of persistence. During infection the signals passed between stem cells and the niche may be blocked or inhibited. Resultantly, stem cells must choose to either adhere or leave in search of a better environment. The heterogeneity that these cells display has immediate consequences for translational therapies involving bone marrow transplant, and the effects that infection might have on these procedures.

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