[PDF][PDF] CD34− cells at the apex of the human hematopoietic stem cell hierarchy have distinctive cellular and molecular signatures

F Anjos-Afonso, E Currie, HG Palmer, KE Foster… - Cell stem cell, 2013 - cell.com
F Anjos-Afonso, E Currie, HG Palmer, KE Foster, DC Taussig, D Bonnet
Cell stem cell, 2013cell.com
In addition to well-characterized CD34+ hematopoietic stem and progenitor cells (HSPCs),
the human hematopoietic stem cell (HSC) hierarchy contains a rare CD34− population with
severe combined immunodeficiency-repopulating capacity. However, little is known about
the molecular characteristics of these CD34− cells or their relationship to the CD34+
populations. Here, we show that the self-renewing Lin− CD34− CD38− CD93 hi population
contains cells that not only function as HSCs, but can also be placed above the CD34+ …
Summary
In addition to well-characterized CD34+ hematopoietic stem and progenitor cells (HSPCs), the human hematopoietic stem cell (HSC) hierarchy contains a rare CD34 population with severe combined immunodeficiency-repopulating capacity. However, little is known about the molecular characteristics of these CD34 cells or their relationship to the CD34+ populations. Here, we show that the self-renewing LinCD34CD38CD93hi population contains cells that not only function as HSCs, but can also be placed above the CD34+ populations in the hematopoietic hierarchy. These cells have an active Notch pathway, in which signaling through Delta4 is crucial for maintenance of the primitive state, and combined signals from Jagged1 and TGF-β are important in controlling its quiescence. They are also refractory to proliferative signals and show a repressed canonical Wnt pathway, in part regulated by Notch. Overall, therefore, CD34 cells represent an immature and quiescent human HSC population maintained through a distinctive network of cellular signaling interactions.
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