RT Journal Article
SR Electronic
T1 Neogenin-1 distinguishes between myeloid-biased and balanced Hoxb5+ long-term hematopoietic stem cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 608398
DO 10.1101/608398
A1 Gunsagar S. Gulati
A1 Monika Zukowska
A1 Joseph Noh
A1 Allison Zhang
A1 Rahul Sinha
A1 Benson George
A1 Daniel J. Wesche
A1 Irving L. Weissman
A1 Krzysztof Szade
YR 2019
UL http://biorxiv.org/content/early/2019/04/27/608398.abstract
AB Hematopoietic stem cells (HSCs) self-renew and generate all blood cells. Recent studies with single-cell transplants and lineage tracing suggest that adult HSCs are diverse in their reconstitution and lineage potentials. However, prospective isolation of these subpopulations has remained challenging. Here, we identify Neogenin-1 (NEO1) as a novel surface marker on a fraction of mouse HSCs labeled with Hoxb5, a specific reporter of long-term HSCs (LT-HSCs). We show that NEO1+Hoxb5+ LT-HSCs are more proliferative and expand with age, while NEO1− Hoxb5+ LT-HSCs remain largely quiescent with no significant increase in number. Upon serial transplantation, NEO1+Hoxb5+ LT-HSCs exhibit myeloid-biased differentiation and reduced reconstitution, while NEO1−Hoxb5+ LT-HSCs are lineage-balanced and stably reconstitute recipients. Gene expression comparison further reveals evidence of lineage-priming in the NEO1+ fraction. Finally, transplanted NEO1+Hoxb5+ LT-HSCs rarely generate NEO1−Hoxb5+ LT-HSCs, while NEO1−Hoxb5+ LT-HSCs repopulate both LT-HSC fractions, supporting that NEO1− Hoxb5+ LT-HSCs can hierarchically precede NEO1+Hoxb5+ LT-HSCs.