Myelo-lymphoid lineage restriction occurs in the human haematopoietic stem cell compartment before lymphoid-primed multipotent progenitors

Serena Belluschi, Emily F. Calderbank, Valerio Ciaurro, Blanca Pijuan-Sala, Antonella Santoro, Nicole Mende, Evangelia Diamanti, Kendig Yen Chi Sham, Xiaonan Wang, Winnie W. Y. Lau, Wajid Jawaid, Berthold Göttgens and Elisa Laurenti ()
Additional contact information
Serena Belluschi: University of Cambridge
Emily F. Calderbank: University of Cambridge
Valerio Ciaurro: University of Cambridge
Blanca Pijuan-Sala: University of Cambridge
Antonella Santoro: University of Cambridge
Nicole Mende: University of Cambridge
Evangelia Diamanti: University of Cambridge
Kendig Yen Chi Sham: University of Cambridge
Xiaonan Wang: University of Cambridge
Winnie W. Y. Lau: University of Cambridge
Wajid Jawaid: University of Cambridge
Berthold Göttgens: University of Cambridge
Elisa Laurenti: University of Cambridge

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract Capturing where and how multipotency is lost is crucial to understand how blood formation is controlled. Blood lineage specification is currently thought to occur downstream of multipotent haematopoietic stem cells (HSC). Here we show that, in human, the first lineage restriction events occur within the CD19−CD34+CD38−CD45RA−CD49f+CD90+ (49f+) HSC compartment to generate myelo-lymphoid committed cells with no erythroid differentiation capacity. At single-cell resolution, we observe a continuous but polarised organisation of the 49f+ compartment, where transcriptional programmes and lineage potential progressively change along a gradient of opposing cell surface expression of CLEC9A and CD34. CLEC9AhiCD34lo cells contain long-term repopulating multipotent HSCs with slow quiescence exit kinetics, whereas CLEC9AloCD34hi cells are restricted to myelo-lymphoid differentiation and display infrequent but durable repopulation capacity. We thus propose that human HSCs gradually transition to a discrete lymphoid-primed state, distinct from lymphoid-primed multipotent progenitors, representing the earliest entry point into lymphoid commitment.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-06442-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06442-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-06442-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().