Search

Your search keyword '"Aubert, Léo"' showing total 31 results
Start Over Author "Aubert, Léo"
31 results on '"Aubert, Léo"'

2. Immunotherapeutic targeting of surfaceome heterogeneity in AML

Author

Bordeleau, Marie-Eve, Audemard, Éric, Métois, Arnaud, Theret, Louis, Lisi, Véronique, Farah, Azer, Spinella, Jean-François, Chagraoui, Jalila, Moujaber, Ossama, Aubert, Léo, Khakipoor, Banafsheh, Mallinger, Laure, Boivin, Isabel, Mayotte, Nadine, Hajmirza, Azadeh, Bonneil, Éric, Béliveau, François, Pfammatter, Sybille, Feghaly, Albert, Boucher, Geneviève, Gendron, Patrick, Thibault, Pierre, Barabé, Frédéric, Lemieux, Sébastien, Richard-Carpentier, Guillaume, Hébert, Josée, Lavallée, Vincent-Philippe, Roux, Philippe P., and Sauvageau, Guy

Published
2024
Full Text
View/download PDF

3. CBFA2T3::GLIS2 pediatric acute megakaryoblastic leukemia is sensitive to BCL-XL inhibition by navitoclax and DT2216

Author

Gress, Verena, Roussy, Mathieu, Boulianne, Luc, Bilodeau, Mélanie, Cardin, Sophie, El-Hachem, Nehme, Lisi, Véronique, Khakipoor, Banafsheh, Rouette, Alexandre, Farah, Azer, Théret, Louis, Aubert, Léo, Fatima, Furat, Audemard, Éric, Thibault, Pierre, Bonneil, Éric, Chagraoui, Jalila, Laramée, Louise, Gendron, Patrick, Jouan, Loubna, Jammali, Safa, Paré, Bastien, Simpson, Shawn M., Tran, Thai Hoa, Duval, Michel, Teira, Pierre, Bittencourt, Henrique, Santiago, Raoul, Barabé, Frédéric, Sauvageau, Guy, Smith, Martin A., Hébert, Josée, Roux, Philippe P., Gruber, Tanja A., Lavallée, Vincent-Philippe, Wilhelm, Brian T., and Cellot, Sonia

Published
2024
Full Text
View/download PDF

4. Direct interaction of TrkA/CD44v3 is essential for NGF-promoted aggressiveness of breast cancer cells

Author

Trouvilliez, Sarah, Cicero, Julien, Lévêque, Romain, Aubert, Léo, Corbet, Cyril, Van Outryve, Alexandre, Streule, Karolin, Angrand, Pierre-Olivier, Völkel, Pamela, Magnez, Romain, Brysbaert, Guillaume, Mysiorek, Caroline, Gosselet, Fabien, Bourette, Roland, Adriaenssens, Eric, Thuru, Xavier, Lagadec, Chann, de Ruyck, Jérôme, Orian-Rousseau, Véronique, Le Bourhis, Xuefen, and Toillon, Robert-Alain

Published
2022
Full Text
View/download PDF

5. The Receptor Tyrosine Kinase AXL Is Required at Multiple Steps of the Metastatic Cascade during HER2-Positive Breast Cancer Progression

Author

Goyette, Marie-Anne, primary, Duhamel, Stéphanie, additional, Aubert, Léo, additional, Pelletier, Ariane, additional, Savage, Paul, additional, Thibault, Marie-Pier, additional, Johnson, Radia Marie, additional, Carmeliet, Peter, additional, Basik, Mark, additional, Gaboury, Louis, additional, Muller, William J., additional, Park, Morag, additional, Roux, Philippe P., additional, Gratton, Jean-Philippe, additional, and Côté, Jean-François, additional

Published
2023
Full Text
View/download PDF

6. Human models of NUP98-KDM5A megakaryocytic leukemia in mice contribute to uncovering new biomarkers and therapeutic vulnerabilities

Author

Cardin, Sophie, Bilodeau, Mélanie, Roussy, Mathieu, Aubert, Léo, Milan, Thomas, Jouan, Loubna, Rouette, Alexandre, Laramée, Louise, Gendron, Patrick, Duchaine, Jean, Decaluwe, Hélène, Spinella, Jean-François, Mourad, Stéphanie, Couture, Françoise, Sinnett, Daniel, Haddad, Élie, Landry, Josette-Renée, Ma, Jing, Humphries, R. Keith, Roux, Philippe P., Hébert, Josée, Gruber, Tanja A., Wilhelm, Brian T., and Cellot, Sonia

Published
2019
Full Text
View/download PDF

7. CBFA2T3::GLIS2 Pediatric Acute Megakaryoblastic Leukemia is Sensitive to BCL-XL Inhibition by Navitoclax and DT2216

Author

Gress, Verena, primary, Roussy, Mathieu, additional, Boulianne, Luc, additional, Bilodeau, Mélanie, additional, Cardin, Sophie, additional, EL-Hachem, Nehme, additional, Lisi, Véronique, additional, Khakipoor, Banafsheh, additional, Rouette, Alexandre, additional, Farah, Azer, additional, Théret, Louis, additional, Aubert, Léo, additional, Fatima, Furat, additional, Audemard, Eric, additional, Thibault, Pierre, additional, Bonneil, Éric, additional, Chagraoui, Jalila, additional, Laramée, Louise, additional, Gendron, Patrick, additional, Jouan, Loubna, additional, Jammali, Safa, additional, Paré, Bastien, additional, Simpson, Shawn M., additional, Tran, Thai Hoa, additional, Duval, Michel, additional, Teira, Pierre, additional, Bittencourt, Henrique, additional, Santiago, Raoul, additional, Barabé, Frédéric, additional, Sauvageau, Guy, additional, Smith, Martin A, additional, Hébert, Josée, additional, Roux, Philippe P, additional, Gruber, Tanja A, additional, Lavallée, Vincent-Philippe, additional, Wilhelm, Brian T, additional, and Cellot, Sonia, additional

Published
2023
Full Text
View/download PDF

10. Identification of Novel Cell Surface Therapeutic Targets for KMT2A-Rearranged Acute Myeloid Leukemia

Author

Theret, Louis, primary, Bordeleau, Marie-Eve, additional, Hajmirza, Azadeh, additional, Metois, Arnaud, additional, Moujaber, Ossama, additional, Audemard, Eric, additional, Spinella, Jean-Francois, additional, Chagraoui, Jalila, additional, Aubert, Léo, additional, Farah, Azer, additional, Lisi, Véronique, additional, Bonneil, Eric, additional, Boivin, Isabel, additional, Mayotte, Nadine, additional, MacRae, Tara, additional, Thibault, Pierre, additional, Lemieux, Sébastien, additional, Lavallée, Vincent-Philippe, additional, Hebert, Josee, additional, Sauvageau, Guy, additional, and Roux, Philippe P, additional

Published
2022
Full Text
View/download PDF

12. Direct interaction of TrkA/CD44v3 is essential for NGF-promoted aggressiveness of breast cancer cells

Author

UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, Trouvilliez, Sarah, Cicero, Julien, Lévêque, Romain, Aubert, Léo, Corbet, Cyril, Van Outryve, Alexandre, Streule, Karolin, Angrand, Pierre-Olivier, Völkel, Pamela, Magnez, Romain, Brysbaert, Guillaume, Mysiorek, Caroline, Gosselet, Fabien, Bourette, Roland, Adriaenssens, Eric, Thuru, Xavier, Lagadec, Chann, de Ruyck, Jérôme, Orian-Rousseau, Véronique, Le Bourhis, Xuefen, Toillon, Robert-Alain, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, Trouvilliez, Sarah, Cicero, Julien, Lévêque, Romain, Aubert, Léo, Corbet, Cyril, Van Outryve, Alexandre, Streule, Karolin, Angrand, Pierre-Olivier, Völkel, Pamela, Magnez, Romain, Brysbaert, Guillaume, Mysiorek, Caroline, Gosselet, Fabien, Bourette, Roland, Adriaenssens, Eric, Thuru, Xavier, Lagadec, Chann, de Ruyck, Jérôme, Orian-Rousseau, Véronique, Le Bourhis, Xuefen, and Toillon, Robert-Alain

Abstract

Background: CD44 is a multifunctional membrane glycoprotein. Through its heparan sulfate chain, CD44 presents growth factors to their receptors. We have shown that CD44 and Tropomyosin kinase A (TrkA) form a complex following nerve growth factor (NGF) induction. Our study aimed to understand how CD44 and TrkA interact and the consequences of inhibiting this interaction regarding the pro-tumoral effect of NGF in breast cancer. Methods: After determining which CD44 isoforms (variants) are involved in forming the TrkA/CD44 complex using proximity ligation assays, we investigated the molecular determinants of this interaction. By molecular modeling, we isolated the amino acids involved and confirmed their involvement using mutations. A CD44v3 mimetic peptide was then synthesized to block the TrkA/CD44v3 interaction. The effects of this peptide on the growth, migration and invasion of xenografted triple-negative breast cancer cells were assessed. Finally, we investigated the correlations between the expression of the TrkA/CD44v3 complex in tumors and histo-pronostic parameters. Results: We demonstrated that isoform v3 (CD44v3), but not v6, binds to TrkA in response to NGF stimulation. The final 10 amino acids of exon v3 and the TrkA H112 residue are necessary for the association of CD44v3 with TrkA. Functionally, the CD44v3 mimetic peptide impairs not only NGF-induced RhoA activation, clonogenicity, and migration/invasion of breast cancer cells in vitro but also tumor growth and metastasis in a xenograft mouse model. We also detected TrkA/CD44v3 only in cancerous cells, not in normal adjacent tissues.

Published
2022

13. Additional file 3 of Direct interaction of TrkA/CD44v3 is essential for NGF-promoted aggressiveness of breast cancer cells

Author

Trouvilliez, Sarah, Cicero, Julien, Lévêque, Romain, Aubert, Léo, Corbet, Cyril, Van Outryve, Alexandre, Streule, Karolin, Angrand, Pierre-Olivier, Völkel, Pamela, Magnez, Romain, Brysbaert, Guillaume, Mysiorek, Caroline, Gosselet, Fabien, Bourette, Roland, Adriaenssens, Eric, Thuru, Xavier, Lagadec, Chann, de Ruyck, Jérôme, Orian-Rousseau, Véronique, Le Bourhis, Xuefen, and Toillon, Robert-Alain

Subjects
animal structures, nervous system
Abstract

Additional file 3: Supplementary Figure 1. Validation of the ectopic expression of CD44 and/or TrkA in COS-7 cells. The expression of all CD44 isoforms (A), CD44 variant 3 (B), CD44 variant 6 (C) and TrkA (hyaluronan [HA]; D) was evaluated by RT–qPCR (normalized using PUM-1). No expression of CD44, CD44 variants [3 or 6] or TrkA was detected in COS-7 cells (A-D) compared with that in cells transfected with the expression plasmid carrying each protein. Supplementary figure 2. TrkA does not interact with CD44s or CD44v6. Wild-type cos7 cells (A) or CD44S- (B) or CD44v6 (C) cells transfected with TrkA were treated with 100 ng/ml NGF (0, 5 or 30 min) and fixed. Quantification of the PLA results was performed using ImageJ software (30 randomly chosen fields per condition of three different experiments). Statistical analyses were performed using one-way ANOVA followed by Bonferroni’s posttest. The error bars represent the standard error of the mean (S.E.M.); ns, not significant. Supplementary Figure 3. CD44v3 and TrkA are recruited to the plasma membrane through NGF stimulation. CD44v3 and CD44v6 levels at the plasma membrane were assessed by flow cytometry (A-D). The plasma membrane and total TrkA and CD44v3 levels were also quantified by confocal microscopy (E-H). Statistical analyses were performed using one-way ANOVA followed by Bonferroni’s posttest. The error bars represent the standard error of the mean (S.E.M.); * p

Published
2022
Full Text
View/download PDF

14. 3173 – HUMAN MODELS OF PEDIATRIC CBFA2T3-GLIS2 ACUTE MEGAKARYOBLASTIC LEUKEMIA CONTRIBUTE TO UNCOVER THERAPEUTIC VULNERABILITIES

Author

Roussy, Mathieu, primary, Boulianne, Luc, additional, Hachem, Nehme, additional, Theret, Louis, additional, Gress, Verena, additional, Aubert, Léo, additional, Bilodeau, Mélanie, additional, Cardin, Sophie, additional, Laramée, Louise, additional, Lisi, Véronique, additional, Rouette, Alexandre, additional, Roux, Philippe, additional, Lavallée, Vincent-Philippe, additional, and Cellot, Sonia, additional

Published
2022
Full Text
View/download PDF

16. 3058 – SURFACE PROTEOMICS REVEALS NOVEL POTENTIAL AML ANTIGENS FOR IMMUNOTHERAPEUTIC TARGETING

Author

Bordeleau, Marie-Eve, primary, Thérêt, Louis, additional, Audemard, Éric, additional, Spinella, Jean-François, additional, Aubert, Léo, additional, Boivin, Isabel, additional, Bonneil, Éric, additional, Thibault, Pierre, additional, Lemieux, Sébastien, additional, Lavallée, Vincent-Philippe, additional, Hébert, Josée, additional, Roux, Philippe, additional, and Sauvageau, Guy, additional

Published
2020
Full Text
View/download PDF

17. NF45 and NF90 Regulate Mitotic Gene Expression by Competing with Staufen-Mediated mRNA Decay

Author

Nourreddine, Sami, primary, Lavoie, Geneviève, additional, Paradis, Justine, additional, Ben El Kadhi, Khaled, additional, Méant, Antoine, additional, Aubert, Léo, additional, Grondin, Benoit, additional, Gendron, Patrick, additional, Chabot, Benoit, additional, Bouvier, Michel, additional, Carreno, Sébastien, additional, and Roux, Philippe P., additional

Published
2020
Full Text
View/download PDF

19. ProNGF increases breast tumor aggressiveness through functional association of TrkA with EphA2

Author

UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, Lévêque, Romain, Corbet, Cyril, Aubert, Léo, Guilbert, Matthieu, Lagadec, Chann, Adriaenssens, Eric, Duval, Jérémy, Finetti, Pascal, Birnbaum, Daniel, Magné, Nicolas, Chopin, Valérie, Bertucci, François, Le Bourhis, Xuefen, Toillon, Robert-Alain, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, Lévêque, Romain, Corbet, Cyril, Aubert, Léo, Guilbert, Matthieu, Lagadec, Chann, Adriaenssens, Eric, Duval, Jérémy, Finetti, Pascal, Birnbaum, Daniel, Magné, Nicolas, Chopin, Valérie, Bertucci, François, Le Bourhis, Xuefen, and Toillon, Robert-Alain

Abstract

ProNGF expression has been linked to several types of cancers including breast cancer, and we have previously shown that proNGF stimulates breast cancer invasion in an autocrine manner through membrane receptors sortilin and TrkA. However, little is known regarding TrkA-associated protein partners upon proNGF stimulation. By proteomic analysis and proximity ligation assays, we found that proNGF binding to sortilin induced sequential formation of the functional sortilin/TrkA/EphA2 complex, leading to TrkA-phosphorylation dependent Akt activation and EphA2-dependent Src activation. EphA2 inhibition using siRNA approach abolished proNGF-stimulated clonogenic growth of breast cancer cell lines. Combinatorial targeting of TrkA and EphA2 dramatically reduced colony formation in vitro, primary tumor growth and metastatic dissemination towards the brain in vivo. Finally, proximity ligation assay in breast tumor samples revealed that increased TrkA/EphA2 proximity ligation assay signals were correlated with a decrease of overall survival in patients. All together, these data point out the importance of TrkA/EphA2 functional association in proNGF-induced tumor promoting effects, and provide a rationale to target proNGF/TrkA/EphA2 axis by alternative methods other than the simple use of tyrosine kinase inhibitors in breast cancer.

Published
2019

20. ProNGF increases breast tumor aggressiveness through functional association of TrkA with EphA2

Author

Lévêque, Romain, primary, Corbet, Cyril, additional, Aubert, Léo, additional, Guilbert, Matthieu, additional, Lagadec, Chann, additional, Adriaenssens, Eric, additional, Duval, Jérémy, additional, Finetti, Pascal, additional, Birnbaum, Daniel, additional, Magné, Nicolas, additional, Chopin, Valérie, additional, Bertucci, François, additional, Le Bourhis, Xuefen, additional, and Toillon, Robert-Alain, additional

Published
2019
Full Text
View/download PDF

22. The Receptor Tyrosine Kinase AXL Is Required at Multiple Steps of the Metastatic Cascade during HER2-Positive Breast Cancer Progression

Author

Goyette, Marie-Anne, primary, Duhamel, Stéphanie, additional, Aubert, Léo, additional, Pelletier, Ariane, additional, Savage, Paul, additional, Thibault, Marie-Pier, additional, Johnson, Radia Marie, additional, Carmeliet, Peter, additional, Basik, Mark, additional, Gaboury, Louis, additional, Muller, William J., additional, Park, Morag, additional, Roux, Philippe P., additional, Gratton, Jean-Philippe, additional, and Côté, Jean-François, additional

Published
2018
Full Text
View/download PDF

25. NGF-induced TrkA/CD44 association is involved in tumor aggressiveness and resistance to lestaurtinib.

Author

UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, Aubert, Léo, Guilbert, Matthieu, Corbet, Cyril, Génot, Elisabeth, Adriaenssens, Eric, Chassat, Thierry, Bertucci, François, Daubon, Thomas, Magné, Nicolas, Le Bourhis, Xuefen, Toillon, Robert-Alain, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, Aubert, Léo, Guilbert, Matthieu, Corbet, Cyril, Génot, Elisabeth, Adriaenssens, Eric, Chassat, Thierry, Bertucci, François, Daubon, Thomas, Magné, Nicolas, Le Bourhis, Xuefen, and Toillon, Robert-Alain

Abstract

There is accumulating evidence that TrkA and its ligand Nerve Growth Factor (NGF) are involved in cancer development. Staurosporine derivatives such as K252a and lestaurtinib have been developed to block TrkA kinase signaling, but no clinical trial has fully demonstrated their therapeutic efficacy. Therapeutic failures are likely due to the existence of intrinsic signaling pathways in cancer cells that impede or bypass the effects of TrkA tyrosine kinase inhibitors. To verify this hypothesis, we combined different approaches including mass spectrometry proteomics, co-immunoprecipitation and proximity ligation assays. We found that NGF treatment induced CD44 binding to TrkA at the plasma membrane and subsequent activation of the p115RhoGEF/RhoA/ROCK1 pathway to stimulate breast cancer cell invasion. The NGF-induced CD44 signaling was independent of TrkA kinase activity. Moreover, both TrkA tyrosine kinase inhibition with lestaurtinib and CD44 silencing with siRNA inhibited cell growth in vitro as well as tumor development in mouse xenograft model; combined treatment significantly enhanced the antineoplastic effects of either treatment alone. Altogether, our results demonstrate that NGF-induced tyrosine kinase independent TrkA signaling through CD44 was sufficient to maintain tumor aggressiveness. Our findings provide an alternative mechanism of cancer resistance to lestaurtinib and indicate that dual inhibition of CD44 and TrkA tyrosine kinase activity may represent a novel therapeutic strategy.

Published
2015

27. Combined use of a trka inhibitor and an epha2 inhibitor for using in the treatment of solid cancers, and method for the prognosis of survival of a patient who has a solid cancer

Author

UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, Corbet, Cyril, Toillon, Robert-Alain, Aubert, Léo, Guilbert, Matthieu, Le Bourhis, Xuefen, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, Corbet, Cyril, Toillon, Robert-Alain, Aubert, Léo, Guilbert, Matthieu, and Le Bourhis, Xuefen

Published
2014

28. Extracellular Signal-Regulated Kinases 1 and 2 Phosphorylate Gab2 To Promote a Negative-Feedback Loop That Attenuates Phosphoinositide 3-Kinase/Akt Signaling.

Author

Xiaocui Zhang, Lavoie, Geneviève, Méant, Antoine, Aubert, Léo, Cargnello, Marie, Haman, André, Trang Hoang, and Roux, Philippe P.

Subjects
PHOSPHOINOSITIDES, MITOGEN-activated protein kinases, ADAPTOR proteins, PROTEIN kinase B, CELLULAR signal transduction, MAST cells
Abstract

The scaffolding adapter protein Gab2 (Grb2-associated binder) promotes cell proliferation, survival, and motility by engaging several signaling pathways downstream of growth factor and cytokine receptors. In particular, Gab2 plays essential roles in mast cells, as it is required for phosphoinositide 3-kinase (PI3K) activation in response to Kit and the high-affinity IgE receptor. While the positive role of Gab2 in PI3K signaling is well documented, very little is known about the mechanisms that attenuate its function. Here we show that Gab2 becomes phosphorylated on multiple proline-directed sites upon stimulation of the Ras/extracellular signal-regulated kinase (ERK) signaling pathway. We demonstrate that ERK1 and ERK2 interact with Gab2 via a novel docking motif, which is required for subsequent Gab2 phosphorylation in response to ERK1/2 activation. We identified four ERK1/2-dependent phosphorylation sites in Gab2 that prevent the recruitment of the p85 regulatory subunit of PI3K. Using bone marrow-derived mast cells to study Gab2-dependent signaling, we found that the inhibition of ERK1/2 activity promotes Akt signaling in response to Kit and the high-affinity IgE receptor. Together, our results indicate that ERK1/2 participates in a negative-feedback loop that attenuates PI3K/Akt signaling in response to various agonists. [ABSTRACT FROM AUTHOR]

Published
2017
Full Text
View/download PDF

29. EPCR expression marks UM171-expanded CD34+cord blood stem cells

Author

Fares, Iman, Chagraoui, Jalila, Lehnertz, Bernhard, MacRae, Tara, Mayotte, Nadine, Tomellini, Elisa, Aubert, Léo, Roux, Philippe P., and Sauvageau, Guy

Abstract

A small subset of human cord blood CD34+cells express endothelial protein C receptor (EPCR/CD201/PROCR) when exposed to the hematopoietic stem cell (HSC) self-renewal agonist UM171. In this article, we show that EPCR-positive UM171-treated cells, as opposed to EPCR-negative cells, exhibit robust multilineage repopulation and serial reconstitution ability in immunocompromised mice. In contrast to other stem cell markers, such as CD38, EPCR expression is maintained when cells are introduced in culture, irrespective of UM171 treatment. Although engineered overexpression of EPCR fails to reproduce the effects of UM171 on HSC activity, its expression is required for the repopulating activity of human HSCs. Altogether, our results indicate that EPCR is a reliable and cell culture–compatible marker of UM171-expanded human cord blood HSCs.

Published
2017
Full Text
View/download PDF

30. CBFA2T3::GLIS2 Pediatric Acute Megakaryoblastic Leukemia is Sensitive to BCL-XLInhibition by Navitoclax and DT2216

Author

Gress, Verena, Roussy, Mathieu, Boulianne, Luc, Bilodeau, Mélanie, Cardin, Sophie, El-Hachem, Nehme, Lisi, Véronique, Khakipoor, Banafsheh, Rouette, Alexandre, Farah, Azer, Théret, Louis, Aubert, Léo, Fatima, Furat, Audemard, Éric, Thibault, Pierre, Bonneil, Éric, Chagraoui, Jalila, Laramée, Louise, Gendron, Patrick, Jouan, Loubna, Jammali, Safa, Paré, Bastien, Simpson, Shawn M., Tran, Thai Hoa, Duval, Michel, Teira, Pierre, Bittencourt, Henrique, Santiago, Raoul, Barabé, Frédéric, Sauvageau, Guy, Smith, Martin A., Hébert, Josée, Roux, Philippe P., Gruber, Tanja A., Lavallée, Vincent-Philippe, Wilhelm, Brian T., and Cellot, Sonia

Abstract

1.Cord blood–derived CBFA2T3::GLIS2 high-fidelity AMKL models contribute to capture the cellular and molecular heterogeneity of the disease2.BCL-XLinhibition is revealed as a therapeutic vulnerability in CG2 and NUP98r AMKL

Published
2023
Full Text
View/download PDF

31. EPCR expression marks UM171-expanded CD34+ cord blood stem cells.

Author

Fares, Iman, Chagraoui, Jalila, Lehnertz, Bernhard, MacRae, Tara, Mayotte, Nadine, Tomellini, Elisa, Aubert, Léo, Roux, Philippe P., and Sauvageau, Guy

Subjects
*CORD blood, *ENDOTHELIAL cells, *GENE expression, *STEM cell factor, *LABORATORY mice
Abstract

A small subset of human cord blood CD34+ cells express endothelial protein C receptor (EPCR/CD201/PROCR) when exposed to the hematopoietic stem cell (HSC) self-renewal agonist UM171. In this article, we show that EPCR-positive UM171-treated cells, as opposed to EPCR-negative cells, exhibit robust multilineage repopulation and serial reconstitution ability in immunocompromised mice. In contrast to other stem cell markers, such as CD38, EPCR expression is maintained when cells are introduced in culture, irrespective of UM171 treatment. Although engineered overexpression of EPCR fails to reproduce the effects of UM171 on HSC activity, its expression is required for the repopulating activity of human HSCs. Altogether, our results indicate that EPCR is a reliable and cell culture-compatible marker of UM171-expanded human cord blood HSCs. [ABSTRACT FROM AUTHOR]

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results