The following study was conducted by Scientists from Wellcome MRC Cambridge Stem Cell Institute, University of Cambridge, Hills Road, Cambridge, UK; Department of Haematology, University of Cambridge, Cambridge, UK; York Biomedical Research Institute, Department of Biology, University of York, York, UK. Study is published in Stem Cell Reports Journal – Cell Press Publishing as detailed below.
Stem Cell Reports Journal – Cell Press Publishing (2021)
Hematopoietic Stem Cells Retain Functional Potential and Molecular Identity in Hibernation Cultures
Highlights
- Fully functional single HSCs are maintained in the absence of a hematopoietic niche
- scRNA-seq identifies the molecular regulators of HSC hibernation and SCF activation
- Human HSC activity can be retained in hibernation cultures
- Single HSCs can be transduced with lentiviral constructs during hibernation
Summary
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.
Source:
Stem Cell Reports Journal – Cell Press Publishing
URL: https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(21)00197-1
Citation:
Oedekoven, C.A., Belmonte, M., Bode, D., Hamey, F.K., Shepherd, M.S., Che, J.L.C., Boyd, G., McDonald, C., Belluschi, S., Diamanti, E., Bastos, H.P., Bridge, K.S., Göttgens, B., Laurenti, E., Kent, D.G., 2021. Hematopoietic stem cells retain functional potential and molecular identity in hibernation cultures. Stem Cell Reports 16(6), 1614-1628.
