Evaluation of the role of CD47 in sickle cell disease

CD47 is a self-marker expressed on the surface of RBCs and work to prevent the process of phagocytosis. SIRPα is the ligand of CD47 that is expressed on the surface of phagocytic cells, such as macrophages, to control the removal of dead/diseased cells. This study aimed to examine the expression of CD47 on RBCs and SIRPα on PBMC cells in SCD patients and the apoptosis of SCD RBCs. We also measured the levels of pro-inflammatory cytokines in SCD patients and correlated it with the cell surface marker expression of CD47 and SIRPα to determine whether CD47 and/or SIRPα played a role in promoting the pro-inflammatory phenotype in SCD. Whole blood samples were drawn from SCD patients, and healthy control and PBMC were isolated and stained with SIRPα. Change in CD47, apoptosis by annexin V marker, and pro-inflammatory cytokines were measured and correlation among these variants was determined. The expression of CD47 was significantly decreased and the apoptosis was increased in RBCs of SCD patients. A higher level of pro-inflammatory cytokines, IL-6 and IL-1β, was found in SCD patients and IL-1β was found to be inversely correlated with SIRPα expression. Our data showed that CD47 of erythrocytes of SCD samples is reduced and that the apoptosis is increased in those patients. Based on the role of CD47, we suggest that increased apoptosis in SCD would be impacted by the reduced level of CD47. An inverse relationship was found between SIRPα marker on PBMC and the increased production of pro-inflammatory cytokines in SCD.

Multi-Modal Profiling of Human Fetal Liver-Derived Hematopoietic Stem Cells Reveals the Molecular Signature of Engraftment Potential

SUMMARYThe human hematopoietic stem cell (HSC) harbors remarkable regenerative potential that can be harnessed therapeutically. During early development, HSCs in the fetal liver (FL) undergo active expansion while simultaneously retaining robust engraftment capacity, yet the underlying molecular program responsible for their efficient engraftment remains unclear. We profiled 26,407 FL cells at both transcriptional and protein levels including over 7,000 highly enriched and functional FL HSCs to establish a detailed molecular signature of engraftment potential. Integration of transcript and linked cell surface marker expression revealed a generalizable signature defining functional FL HSCs and allowed for the stratification of enrichment strategies with high translational potential. This comprehensive, multi-modal profiling of engraftment capacity connects a critical biological function at a key developmental timepoint with its underlying molecular drivers, serving as a useful resource for the field.