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Cdc42 and aging of human HSC
among HSC, thus it remains unclear whether changes in clonality exist already among aged HSC.44–46 We did not determine in this study clonality among the small number of HSC transplanted into animals, as this remains techni- cally very challenging.
In summary, we identified novel age-related phenotypes of human HSC and provide evidence of inter-species paral- lels as well as differences to support translational studies in the aging field. Our data supports that age-related pheno- types that are indicators of the function of aged HSC (Cdc42 activity, polarity, reconstitution potential in xenografts) are malleable in human HSC by inhibition of the age-related elevated activity of Cdc42. This might therefore present a new possibility to improve autologous stem cell transplants of aged donors.
Disclosures
No conflicts of interest to disclose.
Contributions
AA, HG was involved in study design, interpretation and manuscript writing; AA performed and analyzed experiments;
RE, MK and AL provided aged samples; AK and KS per- formed experiments; KS, AV and KE assisted in cell sorting procedures; VS supported in transplantation and bone marrow aspiration; YZ and MCF assisted in study design; AL, RE, MK and MCF reviewed and edited the manuscript.
Acknowledgements
We would like to thank the Flow Cytometry Core and Imaging Core Facilities and the Tierforschungszentrum at the University of Ulm for their support. We also thank Jeffrey Bailey for excellent training in the bone marrow aspiration tech- nique, Aishlin Hassan and Kalpana Nattamai for their techni- cal support at Cincinnati Children’s Hospital Medical Center (CCHMC).
Funding
This study was supported with funding from the DFG, GRK1789 (CEMMA) to HG and AA.
Data sharing statemen
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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