Temporal multimodal single-cell profiling of native hematopoiesis illuminates altered differentiation trajectories with age

Anna Konturek-Ciesla, Parashar Dhapola, Qinyu Zhang, Petter Säwén, Haixia Wan, Göran Karlsson, David Bryder

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

Aging negatively affects hematopoiesis, with consequences for immunity and acquired blood cell disorders. Although impairments in hematopoietic stem cell (HSC) function contribute to this, the in vivo dynamics of such changes remain obscure. Here, we integrate extensive longitudinal functional assessments of HSC-specific lineage tracing with single-cell transcriptome and epitope profiling. In contrast to recent suggestions from single-cell RNA sequencing alone, our data favor a defined structure of HSC/progenitor differentiation that deviates substantially from HSC-derived hematopoiesis following transplantation. Native age-dependent attrition in HSC differentiation manifests as drastically reduced lymphoid output through an early lymphoid-primed progenitor (MPP Ly-I). While in vitro activation fails to rescue lymphoid differentiation from most aged HSCs, robust lymphopoiesis can be achieved by culturing elevated numbers of candidate HSCs. Therefore, our data position rare chronologically aged HSC clones, fully competent at producing lymphoid offspring, as a prime target for approaches aimed to improve lymphopoiesis in the elderly.

Originalspråkengelska
Artikelnummer112304
TidskriftCell Reports
Volym42
Nummer4
DOI
StatusPublished - 2023

Ämnesklassifikation (UKÄ)

  • Cell- och molekylärbiologi

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