Abstract
The human hematopoietic stem cell harbors remarkable regenerative potential that can be harnessed therapeutically. During early development, hematopoietic stem cells in the fetal liver undergo active expansion while simultaneously retaining robust engraftment capacity, yet the underlying molecular program responsible for their efficient engraftment remains unclear. Here, we profile 26,407 fetal liver cells at both the transcriptional and protein level including ~7,000 highly enriched and functional fetal liver hematopoietic stem cells to establish a detailed molecular signature of engraftment potential. Integration of transcript and linked cell surface marker expression reveals a generalizable signature defining functional fetal liver hematopoietic stem cells and allows for the stratification of enrichment strategies with high translational potential. More precisely, our integrated analysis identifies CD201 (endothelial protein C receptor (EPCR), encoded by PROCR) as a marker that can specifically enrich for engraftment potential. This comprehensive, multi-modal profiling of engraftment capacity connects a critical biological function at a key developmental timepoint with its underlying molecular drivers. As such, it serves as a useful resource for the field and forms the basis for further biological exploration of strategies to retain the engraftment potential of hematopoietic stem cells ex vivo or induce this potential during in vitro hematopoietic stem cell generation.
Highlights
The human hematopoietic stem cell harbors remarkable regenerative potential that can be harnessed therapeutically
The CD34− live cells were further subdivided into GYPA+ and GYPA− via fluorescence activated cell sorting (FACS) to capture populations of maturing erythroid progenitors that constitute a sizeable portion of the fetal liver (FL) at this stage in development (CD34−GYPA+)
Following data processing and quality control, this resulted in a total of 26,407 FL cells profiled from one fetal liver, divided across the following fractions: 8735 CD34+bulk cells, 7235 GPI-80+ cells, 6793 CD34+ and flowthrough (CD34−)GYPA− cells and 3644 CD34−GYPA− cells (Supplementary Fig. 1a)
Summary
The human hematopoietic stem cell harbors remarkable regenerative potential that can be harnessed therapeutically. Our integrated analysis identifies CD201 (endothelial protein C receptor (EPCR), encoded by PROCR) as a marker that can enrich for engraftment potential This comprehensive, multi-modal profiling of engraftment capacity connects a critical biological function at a key developmental timepoint with its underlying molecular drivers. Further dissection of this engraftment profile reveals signatures highlighting the importance of proteome integrity maintenance, as well as the prominent expression of factors linked to aging and the concomitant decline of HSC functionality This comprehensive characterization of the engraftment signature of FL HSCs using multi-modal profiling to define an essential biological function at a key developmental timepoint will serve as a useful resource for the field. Our interactive dataset is freely available to the scientific community through the following platform: https://engraftable-hsc.cells.ucsc.edu
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
