AI Article Synopsis

  • Researchers studied 26,407 fetal liver cells to understand the molecular mechanisms behind the engraftment potential of hematopoietic stem cells, focusing on the expansion phase during early development.
  • They identified a comprehensive molecular signature and a specific surface marker, CD201 (EPCR), that can enhance the engraftment capacity of these stem cells.
  • This research provides valuable insights and tools for future studies aimed at improving stem cell therapies by retaining or inducing engraftment potential in lab-grown hematopoietic stem cells.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888592PMC
http://dx.doi.org/10.1038/s41467-022-28616-xDOI Listing

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