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Single-Cell Studies Help to Define Early Human Hematopoiesis

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Review of “Single cell resolution of human hemato-endothelial cells defines transcriptional signatures of hemogenic endothelium” from STEM CELLS by Stuart P. Atkinson

The production of mammalian multipotent hematopoietic stem and progenitor cells (HSPCs) requires the endothelial-to-hematopoietic transition (EHT) of hemogenic endothelial cells (HECs). While lineage-tracing studies have generated a great deal of valuable data on the EHT and other processes at play at the onset of definitive hematopoiesis [1-3], there still exists a great deal more information for us to discern.

To achieve a better understanding of definitive hematopoiesis in humans, researchers from the laboratory of Dan S. Kaufman (University of California-San Diego, USA) recently employed single-cell RNA sequencing to define single HECs and HPSCs differentiated from human embryonic stem cells (hESCs). The authors hope that the findings of their new STEM CELLS study will serve to identify novel stage-specific biomarkers and to improve definitive hematopoietic cell differentiation from human pluripotent stem cells [4].

Angelos et al. employed a previously developed hESC reporter line combined with immunophenotypic profiling [5] to sort and analyze single human vascular-like adherent HECs transitioning into non-adherent HSPCs for the first time. Bioinformatic analysis suggested that HECs and HSPCs shared a common developmental pathway as they displayed transcriptional overlap and shared heightened expression levels for genes implicated in hemogenic endothelial transcriptional networks (ERG, GATA2, and FLI). 

Interestingly, the authors also applied these datasets to identify potentially interesting new biomarkers for human HEC/HPCs, including TIMP3, ESAM, RHOJ, and DLL4. However, transcriptional profiles generated from HECs and HSPCs shared little commonality with those from vascular endothelial cells lacking hematopoietic potential, which displayed a more heterogeneous pattern of gene expression. 

The authors hope that this new insight into early human hematopoietic development will aid the efforts of many groups to generate long-term, multilineage engrafting HSPCs from both hESCs and human induced pluripotent stem cells to provide a patient-specific treatment for a wide range of diseases and disorders.

To stay up to date with more single-cell studies and new advances in human hematopoiesis, stay tuned to the Stem Cells Portal!

References

  1. Bertrand JY, Chi NC, Santoso B, et al., Haematopoietic stem cells derive directly from aortic endothelium during development. Nature 2010;464:108.
  2. Rafii S, Kloss CC, Butler JM, et al., Human ESC-derived hemogenic endothelial cells undergo distinct waves of endothelial to hematopoietic transition. Blood 2013;121:770-780.
  3. Eilken HM, Nishikawa S-I, and Schroeder T, Continuous single-cell imaging of blood generation from haemogenic endothelium. Nature 2009;457:896.
  4. Angelos MG, Abrahante JE, Blum RH, et al., Single Cell Resolution of Human Hematoendothelial Cells Defines Transcriptional Signatures of Hemogenic Endothelium. STEM CELLS 2018;36:206-217.
  5. Ferrell PI, Xi J, Ma C, et al., The RUNX1 +24 Enhancer and P1 Promoter Identify a Unique Subpopulation of Hematopoietic Progenitor Cells Derived from Human Pluripotent Stem Cells. STEM CELLS 2015;33:1130-1141.