A comprehensive single cell transcriptional landscape of human hematopoietic progenitors

Danilo Pellin, Mariana Loperfido, Cristina Baricordi, Samuel L. Wolock, Annita Montepeloso, Olga K. Weinberg, Alessandra Biffi, Allon M. Klein () and Luca Biasco ()
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Danilo Pellin: Harvard Medical School
Mariana Loperfido: Harvard Medical School
Cristina Baricordi: Harvard Medical School
Samuel L. Wolock: Harvard Medical School
Annita Montepeloso: Harvard Medical School
Olga K. Weinberg: Boston Children’s Hospital and Harvard Medical School
Alessandra Biffi: Harvard Medical School
Allon M. Klein: Harvard Medical School
Luca Biasco: Harvard Medical School

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract Hematopoietic Stem/Progenitor cells (HSPCs) are endowed with the role of maintaining a diverse pool of blood cells throughout the human life. Despite recent efforts, the nature of the early cell fate decisions remains contentious. Using single-cell RNA-Seq, we show that existing approaches to stratify bone marrow CD34+ cells reveal a hierarchically-structured transcriptional landscape of hematopoietic differentiation. Still, this landscape misses important early fate decisions. We here provide a broader transcriptional profiling of bone marrow lineage negative hematopoietic progenitors that recovers a key missing branchpoint into basophils and expands our understanding of the underlying structure of early adult human haematopoiesis. We also show that this map has strong similarities in topology and gene expression to that found in mouse. Finally, we identify the sialomucin CD164, as a reliable marker for the earliest branches of HSPCs specification and we showed how its use can foster the design of alternative transplantation cell products.

Date: 2019
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DOI: 10.1038/s41467-019-10291-0

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