P2Y-like receptor, GPR105 (P2Y14), identifies and mediates chemotaxis of bone-marrow hematopoietic stem cells.
Hematopoiesis in mammals undergoes a developmental shift in location from fetal liver to bone marrow accompanied by a gradual transition from highly proliferative to deeply quiescent stem cell populations. P2Y receptors are G-protein-coupled nucleotide receptors participating in vascular and immune responses to injury. We identified a P2Y-like receptor for UDP-conjugated sugars, GPR105 (P2Y14), with restricted expression on primitive cells in the hematopoietic lineage. Anti-GPR105 antibody selectively isolated a subset of hematopoietic cells within the fetal bone marrow, but not in the fetal liver, that was enriched for G0 cell cycle status and for in vitro stem-cell-like multipotential long-term culture capability. Conditioned media from bone marrow stroma induced receptor activation and chemotaxis that was sensitive to G alpha i and anti-receptor antibody inhibition. GPR105 is a G-protein-coupled receptor identifying a quiescent, primitive population of hematopoietic cells restricted to bone marrow. It mediates primitive cell responses to specific hematopoietic microenvironments and extends the known immune system functions of P2Y receptors to the stem cell level. These data suggest a new class of receptors participating in the regulation of the stem cell compartment.
Lee
Byeong-Chel
BC
Center for Regenerative Medicine and Technology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA.
Cheng
Tao
T
Adams
Gregor B
GB
Attar
Eyal C
EC
Miura
Nobuyuki
N
Lee
Sean Bong
SB
Saito
Yoriko
Y
Olszak
Ivona
I
Dombkowski
David
D
Olson
Douglas P
DP
Hancock
Julie
J
Choi
Peter S
PS
Haber
Daniel A
DA
Luster
Andrew D
AD
Scadden
David T
DT
D036541:ADP-ribosyl Cyclase / Q000032:analysis; D051997:ADP-ribosyl Cyclase 1; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D019556:COS Cells; D002453:Cell Cycle; D019070:Cell Lineage; D002469:Cell Separation; D002478:Cells, Cultured; D002633:Chemotaxis; D003114:Colony-Forming Units Assay; D017077:Culture Media, Conditioned; D005434:Flow Cytometry; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D008099:Liver / Q000737:chemistry / Q000196:embryology; D008562:Membrane Glycoproteins; D051379:Mice; D008969:Molecular Sequence Data; D043562:Receptors, G-Protein-Coupled; D018048:Receptors, Purinergic P2 / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D058470:Receptors, Purinergic P2Y; D016192:Resting Phase, Cell Cycle; D014162:Transfection
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D018952:Antigens, CD34; D017077:Culture Media, Conditioned; D008562:Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D018048:Receptors, Purinergic P2; D058470:Receptors, Purinergic P2Y; C509795:P2ry14 protein, mouse; C498154:CD38 protein, human; C498155:Cd38 protein, mouse; C518528:P2Y14 receptor, human