Gpr171, a putative P2Y-like receptor, negatively regulates myeloid differentiation in murine hematopoietic progenitors
Open accessAbstract
Gpr171 is an orphan G-protein-coupled receptor putatively related to the P2Y family of purinergic receptors (P2YRs) for extracellular nucleotides, a group of mediators previously shown to regulate hematopoietic progenitor cells. No information is currently available on the ligand responsible for Gpr171 activation and its biological role remains unknown. We reconstructed Gpr171 phylogenesis in mice and confirmed that Gpr171 is evolutionally related to members of a P2Y gene-cluster localized on mouse chromosome 3. As a first step toward unveiling a role for Gpr171, we investigated its expression profile in murine hematopoietic cells. As opposed to other P2YRs, we found that Gpr171 expression is down-regulated in monocytes and granulocytes, suggesting a negative role in myeloid lineage specification. To test Gpr171 functional role, we next enforced Gpr171 expression in a myeloblastic cell line (32D cells) and in primary Sca-1(+) hematopoietic progenitors, and observed a decreased expression of myeloid markers upon induction of Gpr171, as well as an increased generation of colonies in vitro. Conversely, Gpr171 silencing induced opposite results, diminishing the expression of myeloid markers and the clonogenic potential of 32D cells. In vivo, mice transplanted with hematopoietic progenitor cells overexpressing Gpr171 displayed a significant reduction in the percentage of Mac-1(+)Gr-1(-) cells. As a preliminary step in the investigation of Gpr171 role in murine hematopoiesis, our findings indicate that the orphan receptor Gpr171 negatively regulates myeloid differentiation. Together with phylogenic analyses, our data suggest that Gpr171 may have followed a separate evolutionary pathway as compared to other P2YRs belonging to the same gene cluster.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
P2ry13 is an ADP receptor and part of the G-protein coupled receptor family-it is thought to play a role in hematopoiesis and immune function.
“P2ry13 is an ADP receptor and part of the G-protein coupled receptor family—it is thought to play a role in hematopoiesis and immune function (97).”
From The Transcriptional Landscape of Microglial Genes in Aging and Neurodegenerative Disease (2019) · cites this paper as [97]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Tmbase-A database of membrane spanning protein segments
Hofmann, K., & Stoffel, W. (1993) · Medical Entomology and Zoology · Cited by 2,257 · see citing works
A Stem Cell Molecular Signature
Ivanova, N. B., Dimos, J. T., Schaniel, C., Hackney, J. A., Moore, K. A., & Lemischka, I. R. (2002) · Science · doi:10.1126/science.1073823 · Cited by 1,543 · see citing works
Abbracchio, M. P., Burnstock, G., Boeynaems, J., Barnard, E. A., Boyer, J. L., Kennedy, C., Knight, G. E., Fumagalli, M., Gachet, C., Jacobson, K. A., et al. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.3 · Cited by 1,286 · see citing works
Signal transduction via P2-purinergic receptors for extracellular ATP and other nucleotides
Dubyak, G., & El-Moatassim, C. (1993) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1993.265.3.c577 · Cited by 1,246 · see citing works
Purine and pyrimidine receptors
Burnstock, G. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-6497-0 · Cited by 929 · see citing works
GATA-binding transcription factors in hematopoietic cells
Orkin, S. (1992) · Blood · doi:10.1182/blood.v80.3.575.575 · Cited by 884 · see citing works
Multilineage gene expression precedes commitment in the hemopoietic system.Preprint
Hu, M., Krause, D. S., Greaves, M. F., Sharkis, S. J., Dexter, M., Heyworth, C. M., & Enver, T. (1997) · Genes & Development · doi:10.1101/gad.11.6.774 · Cited by 719 · see citing works
Nucleotide receptors: an emerging family of regulatory molecules in blood cells
Virgilio, F. D., Chiozzi, P., Ferrari, D., Falzoni, S., Sanz, J. M., Morelli, A., Torboli, M., Bolognesi, G., & Baricordi, O. R. (2001) · Blood · doi:10.1182/blood.v97.3.587 · Cited by 702 · see citing works
Pharmacological profiles of cloned mammalian P2Y-receptor subtypes
von Kügelgen, I. (2005) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.08.014 · Cited by 541 · see citing works
Molecular pharmacology of P2Y-receptors
von Kügelgen, I., & Wetter, A. (2000) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s002100000310 · Cited by 483 · see citing works
Purinergic Signalling: Pathophysiological Roles
Abbracchio, M. P., & Burnstock, G. (1998) · The Japanese Journal of Pharmacology · doi:10.1254/jjp.78.113 · Cited by 448 · see citing works
GATA-2 Plays Two Functionally Distinct Roles during the Ontogeny of Hematopoietic Stem Cells
Ling, K.-W., Ottersbach, K., van Hamburg, J. P., Oziemlak, A., Tsai, F., Orkin, S., Ploemacher, R., Hendriks, R., & Dzierzak, E. (2004) · Journal of Experimental Medicine · doi:10.1084/jem.20031556 · Cited by 355 · see citing works
Mouse hematopoietic stem cell identification and analysis
Challen, G. A., Boles, N. C., Lin, K. K., & Goodell, M. A. (2008) · Cytometry Part A · doi:10.1002/cyto.a.20674 · Cited by 350 · see citing works
Self-citationHematopoietic Fingerprints: An Expression Database of Stem Cells and Their Progeny
Chambers, S. M., Boles, N. C., Lin, K. K., Tierney, M., Bowman, T. V., Bradfute, S. B., Chen, A. J., Merchant, A. A., Sirin, O., Weksberg, D. C., et al. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.10.003 · Cited by 318 · see citing works
Self-citationVesicular and conductive mechanisms of nucleotide release
Lazarowski, E. R. (2012) · Purinergic Signalling · doi:10.1007/s11302-012-9304-9 · Cited by 298 · see citing works
Evolutionary origins of the purinergic signalling system
Burnstock, G., & Verkhratsky, A. (2009) · Acta Physiologica · doi:10.1111/j.1748-1716.2009.01957.x · Cited by 277 · see citing works
P2 Purinergic Receptors: Modulation of Cell Function and Therapeutic Potential
Burnstock, G., & Williams, M. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)38983-9 · Cited by 275 · see citing works
Wittenberger, T., Schaller, H., & Hellebrand, S. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4520 · Cited by 197 · see citing works
P2 receptors and extracellular ATP a novel homeostatic pathway in inflammation
Bours, M. J. L. (2011) · Frontiers in Bioscience-Scholar · doi:10.2741/235 · Cited by 160 · see citing works
Notch signalling via RBP‐J promotes myeloid differentiation
Schroeder, T., & Just, U. (2000) · The EMBO Journal · doi:10.1093/emboj/19.11.2558 · Cited by 122 · see citing works
Lemoli, R. M., Ferrari, D., Fogli, M., et al. (2004) · Blood · doi:10.1182/blood-2004-03-0834 · Cited by 119 · see citing works
Self-citationHematopoietic stem cells: generation and self-renewal
Huang, X., Cho, S., & Spangrude, G. J. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402225 · Cited by 109 · see citing works
The extracellular nucleotide UTP is a potent inducer of hematopoietic stem cell migration
Rossi, L., Manfredini, R., Bertolini, F., et al. (2006) · Blood · doi:10.1182/blood-2006-01-035634 · Cited by 98 · see citing works
Self-citationThe sixth sense: hematopoietic stem cells detect danger through purinergic signaling
Rossi, L., Salvestrini, V., Ferrari, D., Virgilio, F. D., & Lemoli, R. M. (2012) · Blood · doi:10.1182/blood-2012-04-422378 · Cited by 80 · see citing works
Self-citationCellular and Molecular Biology of Orphan G Protein‐Coupled Receptors
Oh, D. Y., Kim, K., Kwon, H. B., & Seong, J. Y. (2006) · International review of cytology · doi:10.1016/s0074-7696(06)52003-0 · Cited by 52 · see citing works
Involvement of P2Y receptors in the differentiation of haematopoietic cells
Sak, K., Boeynaems, J., & Everaus, H. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.1102561 · Cited by 45 · see citing works
G Protein-Coupled Receptor Pharmacogenetics
Thompson, M. D., Siminovitch, K. A., & Cole, D. E. C. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-205-2_8 · Cited by 31 · see citing works
Global genetic regulatory networks controlling hematopoietic cell fates
Loose, M., & Patient, R. K. (2006) · Current Opinion in Hematology · doi:10.1097/01.moh.0000231419.15654.7f · Cited by 30 · see citing works
Kostenis, E. (2006) · Current Pharmaceutical Design · doi:10.2174/138161206776873734 · Cited by 27 · see citing works
Chemokine/Receptor Dynamics in the Regulation of Hematopoiesis.
Maekawa, T., & Ishii, T. (2000) · Internal Medicine · doi:10.2169/internalmedicine.39.90 · Cited by 22 · see citing works
The P2Y nucleotide receptors in the human genome
Simon, J., & Barnard, E. A. (2003) · Acta Biologica Hungarica · doi:10.1556/abiol.54.2003.2.8 · Cited by 8 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [22]Burnstock G Purine and pyrimidine receptors Cell Mol Life Sci 2007 64 1471 83 17375261 PMC11149472
Cited by
Sorted by citations
The Transcriptional Landscape of Microglial Genes in Aging and Neurodegenerative Disease
Bonham, L. W., Sirkis, D. W., & Yokoyama, J. S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01170 · Cited by 83 · see citing works
- Authors
- Rossi, L., Lemoli, R. M., & Goodell, M. A.
- Affiliations
- Baylor College of Medicine (US)
- University of Bologna (IT)
- Corresponding author
- Rossi, Lara
- Venue
- Experimental Hematology
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 41
- Issue
- 1
- Pages
- 102-112
- ISSN
- 0301-472X (ISSN-L)
- PMC
- PMC3525765
- OpenAlex
- W2029914847
- Cited by
- 20
- References
- 31
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2017: 2 · 2016: 2 · 2015: 1 · 2013: 2
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Experimental Hematology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- Funders
- National Institute on Aging (R21AG034451)
- National Heart, Lung, and Blood Institute (HL081007, U54HL081007)
- National Cancer Institute (P50CA058183, P30CA125123)
- National Institute of Diabetes and Digestive and Kidney Diseases (R56DK092883, R01DK058192, DK58192, R01DK092883)
- National Institute of Biomedical Imaging and Bioengineering (EB 005173, R01EB005173)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- orphan G protein-coupled receptor, P2Y receptors, purinergic receptors, myeloid differentiation, hematopoietic progenitor cells, clonogenicity, hematopoiesis
- MeSH terms
- Amino Acid Sequence, Animals, Antigens, Ly, Cell Differentiation, Hematopoietic Stem Cells, Membrane Proteins, Mice, Inbred C57BL, Molecular Sequence Data, Myeloid Cells, Receptors, G-Protein-Coupled, Mice, Receptors, Purinergic P2Y
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
