Hematopoietic stem cells retain functional potential and molecular identity in hibernation cultures

Caroline A Oedekoven, Miriam Belmonte, Daniel Bode, Fiona K Hamey, Mairi S Shepherd, James Lok Chi Che, Grace Boyd, Craig McDonald, Serena Belluschi, Evangelia Diamanti, Hugo P Bastos, Katherine S Bridge, Berthold Göttgens, Elisa Laurenti, David G Kent

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Advances in the isolation and gene expression profiling of single hematopoietic stem cells (HSCs) have permitted in-depth resolution of their molecular program. However, long-term HSCs can only be isolated to near purity from adult mouse bone marrow, thereby precluding studies of their molecular program in different physiological states. Here, we describe a powerful 7-day HSC hibernation culture system that maintains HSCs as single cells in the absence of a physical niche. Single hibernating HSCs retain full functional potential compared with freshly isolated HSCs with respect to colony-forming capacity and transplantation into primary and secondary recipients. Comparison of hibernating HSC molecular profiles to their freshly isolated counterparts showed a striking degree of molecular similarity, further resolving the core molecular machinery of HSC self-renewal while also identifying key factors that are potentially dispensable for HSC function, including members of the AP1 complex (Jun, Fos, and Ncor2), Sult1a1 and Cish. Finally, we provide evidence that hibernating mouse HSCs can be transduced without compromising their self-renewal activity and demonstrate the applicability of hibernation cultures to human HSCs.

Original languageEnglish
Pages (from-to)1614-1628
Number of pages15
JournalStem Cell Reports
Issue number6
Early online date6 May 2021
Publication statusPublished - 8 Jun 2021

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