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2. Characterization of the bone marrow niche in patients with chronic myeloid leukemia identifies CXCL14 as a new therapeutic option

Author

Dolinska, Monika, Cai, Huan, Månsson, Alma, Shen, Jingyi, Xiao, Pingnan, Bouderlique, Thibault, Li, Xidan, Leonard, Elory, Chang, Marcus, Gao, Yuchen, Medina, Juan Pablo, Kondo, Makoto, Sandhow, Lakshmi, Johansson, Anne-Sofie, Deneberg, Stefan, Söderlund, Stina, Jädersten, Martin, Ungerstedt, Johanna, Tobiasson, Magnus, Östman, Arne, Mustjoki, Satu, Stenke, Leif, Le Blanc, Katarina, Hellström-Lindberg, Eva, Lehmann, Sören, Ekblom, Marja, Olsson-Strömberg, Ulla, Sigvardsson, Mikael, and Qian, Hong

Published
2023
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3. Surface flow for colonial integration in reef-building corals

Author

Bouderlique, Thibault, Petersen, Julian, Faure, Louis, Abed-Navandi, Daniel, Bouchnita, Anass, Mueller, Benjamin, Nazarov, Murtazo, Englmaier, Lukas, Tesarova, Marketa, Frade, Pedro R., Zikmund, Tomas, Koehne, Till, Kaiser, Jozef, Fried, Kaj, Wild, Christian, Pantos, Olga, Hellander, Andreas, Bythell, John, and Adameyko, Igor

Published
2022
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4. Confocal laser scanning microscopy reveals species-specific differences in distribution of fluorescent proteins in coral tissues.

Author

Marchioro, Giulia M., Coelho, David, Bouderlique, Thibault, Abed-Navandi, Daniel, Schagerl, Michael, D'Angelo, Cecilia, Kruckenhauser, Luise, Adameyko, Igor, and Frade, Pedro R.

Subjects
GREEN fluorescent protein, CONFOCAL fluorescence microscopy, FLUORESCENT proteins, VISIBLE spectra, PHOTOBIOLOGY, CORALS
Abstract

Reef-building corals have a variety of green fluorescent protein (GFP)-like proteins, also known as fluorescent proteins (FPs). These proteins have broad spectral properties covering most of the visible spectrum, with fluorophores fluorescing from cyan to red. However, the role of FPs is still a topic of debate and requires further investigation, particularly in the direction of mapping these FPs within the coral tissue and describing their cell- and tissue-level distributions. This study applied confocal laser scanning microscopy (CLSM) to investigate species-specific differences in the distribution of FPs in three coral taxa (Stylophora sp., Acropora sp., Echinopora sp.), combined with their photoacclimation response and that of associated symbiotic algae to light gradients in a controlled aquarium experiment. CLSM produced high-resolution images that enabled the identification of different FPs, their tissue distribution and quantification of their fluorescence intensity, as well as quantification of symbiont chlorophyll a (chl- a) fluorescence. Emission scans revealed three emission peaks between 490 - 501 nm (cyan, CFPs), 510 - 515 nm (green, GFPs), and 679 nm (chl- a fluorescence signal; Fchl) shared by all three studied species. The distribution of GFPs in Stylophora was concentrated in the intermesenterial muscle bands of the polyp, whereas CFPs were typically located at the tips of the tentacles. In contrast, Acropora and Echinopora exhibited agglomeration of CFPs and GFPs primarily in the epidermis. In general, species-specific differences in FP distribution remained unaltered during the experiment. However, linear regression models showed a significant negative relationship between CFP fluorescence intensity and light irradiance in Stylophora , whereas Echinopora exhibited a negative relation between chlorophyll fluorescence (Fchl) and light. In summary, the CLSM methodology provided a high-resolution tool to study coral FP patterns and symbiont response to irradiance, revealing ecophysiological differences among coral species at the tissue and cellular levels. CLSM has the potential to elucidate the intricacies of coral photobiology within the natural environment and to discern their adaptive responses in situ. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Schwann cell precursors represent a neural crest‐like state with biased multipotency

Author

Kastriti, Maria Eleni, Faure, Louis, Von Ahsen, Dorothea, Bouderlique, Thibault Gerald, Boström, Johan, Solovieva, Tatiana, Jackson, Cameron, Bronner, Marianne, Meijer, Dies, Hadjab, Saida, Lallemend, Francois, Erickson, Alek, Kaucka, Marketa, Dyachuk, Viacheslav, Perlmann, Thomas, Lahti, Laura, Krivanek, Jan, Brunet, Jean‐Francois, Fried, Kaj, and Adameyko, Igor

Published
2022
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7. Single-cell transcriptomics of human embryos identifies multiple sympathoblast lineages with potential implications for neuroblastoma origin

Author

Kameneva, Polina, Artemov, Artem V., Kastriti, Maria Eleni, Faure, Louis, Olsen, Thale K., Otte, Jörg, Erickson, Alek, Semsch, Bettina, Andersson, Emma R., Ratz, Michael, Frisén, Jonas, Tischler, Arthur S., de Krijger, Ronald R., Bouderlique, Thibault, Akkuratova, Natalia, Vorontsova, Maria, Gusev, Oleg, Fried, Kaj, Sundström, Erik, Mei, Shenglin, Kogner, Per, Baryawno, Ninib, Kharchenko, Peter V., and Adameyko, Igor

Published
2021
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11. A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate

Author

Newton, Phillip T., Li, Lei, Zhou, Baoyi, Schweingruber, Christoph, Hovorakova, Maria, Xie, Meng, Sun, Xiaoyan, Sandhow, Lakshmi, Artemov, Artem V., Ivashkin, Evgeny, Suter, Simon, Dyachuk, Vyacheslav, El Shahawy, Maha, Gritli-Linde, Amel, Bouderlique, Thibault, Petersen, Julian, Mollbrink, Annelie, Lundeberg, Joakim, Enikolopov, Grigori, Qian, Hong, Fried, Kaj, Kasper, Maria, Hedlund, Eva, Adameyko, Igor, Sävendahl, Lars, and Chagin, Andrei S.

Published
2019
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12. Characterization of Bone Marrow Niche in Chronic Myeloid Leukemia Patients Identifies CXCL14 as a New Therapeutic Option

Author

Dolinska, Monika, Cai, Huan, Mansson, Alma, Shen, Jingyi, Xiao, Pingnan, Bouderlique, Thibault, Li, Xidan, Leonard, Elory, Chang, Marcus, Gao, Yuchen, Medina Giménez, Juan Pablo, Kondo, Makoto, Sandhow, Lakshmi, Johansson, Anne-Sofie, Deneberg, Stefan, Söderlund, Stina, Jädersten, Martin, Ungerstedt, Johanna S, Tobiasson, Magnus, Östman, Arne, Mustjoki, Satu, Stenke, Leif, Le Blanc, Katarina, Hellstrom-Lindberg, Eva S, Lehmann, Sören, Ekblom, Marja, Olsson-Strömberg, Ulla, Sigvardsson, Mikael, Qian, Hong, Dolinska, Monika, Cai, Huan, Mansson, Alma, Shen, Jingyi, Xiao, Pingnan, Bouderlique, Thibault, Li, Xidan, Leonard, Elory, Chang, Marcus, Gao, Yuchen, Medina Giménez, Juan Pablo, Kondo, Makoto, Sandhow, Lakshmi, Johansson, Anne-Sofie, Deneberg, Stefan, Söderlund, Stina, Jädersten, Martin, Ungerstedt, Johanna S, Tobiasson, Magnus, Östman, Arne, Mustjoki, Satu, Stenke, Leif, Le Blanc, Katarina, Hellstrom-Lindberg, Eva S, Lehmann, Sören, Ekblom, Marja, Olsson-Strömberg, Ulla, Sigvardsson, Mikael, and Qian, Hong

Abstract

Although tyrosine kinase inhibitors (TKIs) are effective in treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be because of bone marrow (BM) niche protection; however, little is known about the underlying mechanisms. Herein, we molecularly and functionally characterize BM niches in patients with CML at diagnosis and reveal the altered niche composition and function in these patients. Long-term culture initiating cell assay showed that the mesenchymal stem cells from patients with CML displayed an enhanced supporting capacity for normal and CML BM CD34+CD38- cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in the BM cellular niches of patients with CML. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and enhanced their response to imatinib in vitro, and CML engraftment in vivo in NSG-SGM3 mice. Importantly, CXCL14 treatment dramatically inhibited CML engraftment in patient-derived xenografted NSG-SGM3 mice, even to a greater degree than imatinib, and this inhibition persisted in patients with suboptimal TKI response. Mechanistically, CXCL14 upregulated inflammatory cytokine signaling but downregulated mTOR signaling and oxidative phosphorylation in CML LSCs. Together, we have discovered a suppressive role of CXCL14 in CML LSC growth. CXCL14 might offer a treatment option targeting CML LSCs., Funding: Institute for Regenerative Medicine, Karolinska Institute Doctoral Edu-cation (KID) [2-1293/2014, 2021-00480]; Stiftelsen Clas Gro-schinskys Minnesfond [M16 50]; Knut and Alice Wallenberg Foundation [KAW 2020.0102]; Cancer Research KI; Incyte Biosciences Nordic; Blodcancerfonden; Nordic Cancer Union and Cancer Foundation Finland

Published
2023
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13. A previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiology

Author

Petersen, Julian, primary, Englmaier, Lukas, additional, Artemov, Artem V., additional, Poverennaya, Irina, additional, Mahmoud, Ruba, additional, Bouderlique, Thibault, additional, Tesarova, Marketa, additional, Deviatiiarov, Ruslan, additional, Szilvásy-Szabó, Anett, additional, Akkuratov, Evgeny E., additional, Pajuelo Reguera, David, additional, Zeberg, Hugo, additional, Kaucka, Marketa, additional, Kastriti, Maria Eleni, additional, Krivanek, Jan, additional, Radaszkiewicz, Tomasz, additional, Gömöryová, Kristína, additional, Knauth, Sarah, additional, Potesil, David, additional, Zdrahal, Zbynek, additional, Ganji, Ranjani Sri, additional, Grabowski, Anna, additional, Buhl, Miriam E., additional, Zikmund, Tomas, additional, Kavkova, Michaela, additional, Axelson, Håkan, additional, Lindgren, David, additional, Kramann, Rafael, additional, Kuppe, Christoph, additional, Erdélyi, Ferenc, additional, Máté, Zoltán, additional, Szabó, Gábor, additional, Koehne, Till, additional, Harkany, Tibor, additional, Fried, Kaj, additional, Kaiser, Jozef, additional, Boor, Peter, additional, Fekete, Csaba, additional, Rozman, Jan, additional, Kasparek, Petr, additional, Prochazka, Jan, additional, Sedlacek, Radislav, additional, Bryja, Vitezslav, additional, Gusev, Oleg, additional, and Adameyko, Igor, additional

Published
2023
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14. Characterization of Bone Marrow Niche in Chronic Myeloid Leukemia Patients Identifies CXCL14 as a New Therapeutic Option

Author

Dolinska, Monika, primary, Cai, Huan, additional, Mansson, Alma, additional, Shen, Jingyi, additional, Xiao, Pingnan, additional, Bouderlique, Thibault, additional, Li, Xidan, additional, Leonard, Elory, additional, Chang, Marcus, additional, Gao, Yuchen, additional, Medina Giménez, Juan Pablo, additional, Kondo, Makoto, additional, Sandhow, Lakshmi, additional, Johansson, Anne-Sofie, additional, Deneberg, Stefan, additional, Söderlund, Stina, additional, Jädersten, Martin, additional, Ungerstedt, Johanna S, additional, Tobiasson, Magnus, additional, Östman, Arne, additional, Mustjoki, Satu, additional, Stenke, Leif, additional, Le Blanc, Katarina, additional, Hellstrom-Lindberg, Eva S, additional, Lehmann, Sören, additional, Ekblom, Marja, additional, Olsson-Strömberg, Ulla, additional, Sigvardsson, Mikael, additional, and Qian, Hong, additional

Published
2023
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15. Surface flow for colonial integration in reef-building corals

Author

Bouderlique, Thibault, Petersen, Julian, Faure, Louis, Abed-Navandi, Daniel, Bouchnita, Anass, Mueller, Benjamin, Nazarov, Murtazo, Englmaier, Lukas, Tesarova, Marketa, Frade, Pedro R., Zikmund, Tomas, Koehne, Till, Kaiser, Jozef, Fried, Kaj, Wild, Christian, Pantos, Olga, Hellander, Andreas, Bythell, John, and Adameyko, Igor

Subjects
Ekologi, colony integration, Ecology, Coral Reefs, Scleractinian coral, Marine engineering, Environment, Marine and estuarine ecology (incl. marine ichthyology), Anthozoa, General Biochemistry, Genetics and Molecular Biology, Species Specificity, mucus, gastrovascular system, Animals, surface hydrodynamics, General Agricultural and Biological Sciences, cnidarian, coral
Abstract

Reef-building corals are endangered animals with a complex colonial organization. Physiological mecha- nisms connecting multiple polyps and integrating them into a coral colony are still enigmatic. Using live im- aging, particle tracking, and mathematical modeling, we reveal how corals connect individual polyps and form integrated polyp groups via species-specific, complex, and stable networks of currents at their surface. These currents involve surface mucus of different concentrations, which regulate joint feeding of the colony. Inside the coral, within the gastrovascular system, we expose the complexity of bidirectional branching streams that connect individual polyps. This system of canals extends the surface area by 4-fold and might improve communication, nutrient supply, and symbiont transfer. Thus, individual polyps integrate via com- plex liquid dynamics on the surface and inside the colony.

Published
2023
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17. FOXO1 and FOXO3 Cooperatively Regulate Innate Lymphoid Cell Development

Author

Luu, Thuy T., primary, Søndergaard, Jonas Nørskov, additional, Peña-Pérez, Lucía, additional, Kharazi, Shabnam, additional, Krstic, Aleksandra, additional, Meinke, Stephan, additional, Schmied, Laurent, additional, Frengen, Nicolai, additional, Heshmati, Yaser, additional, Kierczak, Marcin, additional, Bouderlique, Thibault, additional, Wagner, Arnika Kathleen, additional, Gustafsson, Charlotte, additional, Chambers, Benedict J., additional, Achour, Adnane, additional, Kutter, Claudia, additional, Höglund, Petter, additional, Månsson, Robert, additional, and Kadri, Nadir, additional

Published
2022
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18. FOXO1 and FOXO3 Cooperatively Regulate Innate Lymphoid Cell Development

Author

Luu, Thuy T., Sondergaard, Jonas Norskov, Pena-Perez, Lucia, Kharazi, Shabnam, Krstic, Aleksandra, Meinke, Stephan, Schmied, Laurent, Frengen, Nicolai, Heshmati, Yaser, Kierczak, Marcin, Bouderlique, Thibault, Wagner, Arnika Kathleen, Gustafsson, Charlotte, Chambers, Benedict J., Achour, Adnane, Kutter, Claudia, Höglund, Petter, Månsson, Robert, Kadri, Nadir, Luu, Thuy T., Sondergaard, Jonas Norskov, Pena-Perez, Lucia, Kharazi, Shabnam, Krstic, Aleksandra, Meinke, Stephan, Schmied, Laurent, Frengen, Nicolai, Heshmati, Yaser, Kierczak, Marcin, Bouderlique, Thibault, Wagner, Arnika Kathleen, Gustafsson, Charlotte, Chambers, Benedict J., Achour, Adnane, Kutter, Claudia, Höglund, Petter, Månsson, Robert, and Kadri, Nadir

Abstract

Natural killer (NK) cells play roles in viral clearance and early surveillance against malignant transformation, yet our knowledge of the underlying mechanisms controlling their development and functions remain incomplete. To reveal cell fate-determining pathways in NK cell progenitors (NKP), we utilized an unbiased approach and generated comprehensive gene expression profiles of NK cell progenitors. We found that the NK cell program was gradually established in the CLP to preNKP and preNKP to rNKP transitions. In line with FOXO1 and FOXO3 being co-expressed through the NK developmental trajectory, the loss of both perturbed the establishment of the NK cell program and caused stalling in both NK cell development and maturation. In addition, we found that the combined loss of FOXO1 and FOXO3 caused specific changes to the composition of the non-cytotoxic innate lymphoid cell (ILC) subsets in bone marrow, spleen, and thymus. By combining transcriptome and chromatin profiling, we revealed that FOXO TFs ensure proper NK cell development at various lineage-commitment stages through orchestrating distinct molecular mechanisms. Combined FOXO1 and FOXO3 deficiency in common and innate lymphoid cell progenitors resulted in reduced expression of genes associated with NK cell development including ETS-1 and their downstream target genes. Lastly, we found that FOXO1 and FOXO3 controlled the survival of committed NK cells via gene regulation of IL-15R beta (CD122) on rNKPs and bone marrow NK cells. Overall, we revealed that FOXO1 and FOXO3 function in a coordinated manner to regulate essential developmental genes at multiple stages during murine NK cell and ILC lineage commitment.

Published
2022
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19. FOXO Dictates Initiation of B Cell Development and Myeloid Restriction in Common Lymphoid Progenitors

Author

Pena-Perez, Lucia, Kharazi, Shabnam, Frengen, Nicolai, Krstic, Aleksandra, Bouderlique, Thibault, Hauenstein, Julia, He, Minghui, Somuncular, Ece, Li Wang, Xiaoze, Dahlberg, Carin, Gustafsson, Charlotte, Johansson, Ann-Sofie, Walfridsson, Julian, Kadri, Nadir, Woll, Petter, Kierczak, Marcin, Qian, Hong, Westerberg, Lisa, Luc, Sidinh, Mansson, Robert, Pena-Perez, Lucia, Kharazi, Shabnam, Frengen, Nicolai, Krstic, Aleksandra, Bouderlique, Thibault, Hauenstein, Julia, He, Minghui, Somuncular, Ece, Li Wang, Xiaoze, Dahlberg, Carin, Gustafsson, Charlotte, Johansson, Ann-Sofie, Walfridsson, Julian, Kadri, Nadir, Woll, Petter, Kierczak, Marcin, Qian, Hong, Westerberg, Lisa, Luc, Sidinh, and Mansson, Robert

Abstract

The development of B cells relies on an intricate network of transcription factors critical for developmental progression and lineage commitment. In the B cell developmental trajectory, a temporal switch from predominant Foxo3 to Foxo1 expression occurs at the CLP stage. Utilizing VAV-iCre mediated conditional deletion, we found that the loss of FOXO3 impaired B cell development from LMPP down to B cell precursors, while the loss of FOXO1 impaired B cell commitment and resulted in a complete developmental block at the CD25 negative proB cell stage. Strikingly, the combined loss of FOXO1 and FOXO3 resulted in the failure to restrict the myeloid potential of CLPs and the complete loss of the B cell lineage. This is underpinned by the failure to enforce the early B-lineage gene regulatory circuitry upon a predominantly pre-established open chromatin landscape. Altogether, this demonstrates that FOXO3 and FOXO1 cooperatively govern early lineage restriction and initiation of B-lineage commitment in CLPs.

Published
2022
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20. FOXO Dictates Initiation of B Cell Development and Myeloid Restriction in Common Lymphoid Progenitors

Author

Peña-Pérez, Lucía, primary, Kharazi, Shabnam, additional, Frengen, Nicolai, additional, Krstic, Aleksandra, additional, Bouderlique, Thibault, additional, Hauenstein, Julia, additional, He, Minghui, additional, Somuncular, Ece, additional, Li Wang, Xiaoze, additional, Dahlberg, Carin, additional, Gustafsson, Charlotte, additional, Johansson, Ann-Sofie, additional, Walfridsson, Julian, additional, Kadri, Nadir, additional, Woll, Petter, additional, Kierczak, Marcin, additional, Qian, Hong, additional, Westerberg, Lisa, additional, Luc, Sidinh, additional, and Månsson, Robert, additional

Published
2022
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24. Single-cell transcriptomics of human embryos identifies multiple sympathoblast lineages with potential implications for neuroblastoma origin

Author

Pathologie Pathologen staf, Kameneva, Polina, Artemov, Artem V., Kastriti, Maria Eleni, Faure, Louis, Olsen, Thale K., Otte, Jörg, Erickson, Alek, Semsch, Bettina, Andersson, Emma R., Ratz, Michael, Frisén, Jonas, Tischler, Arthur S., de Krijger, Ronald R., Bouderlique, Thibault, Akkuratova, Natalia, Vorontsova, Maria, Gusev, Oleg, Fried, Kaj, Sundström, Erik, Mei, Shenglin, Kogner, Per, Baryawno, Ninib, Kharchenko, Peter V., Adameyko, Igor, Pathologie Pathologen staf, Kameneva, Polina, Artemov, Artem V., Kastriti, Maria Eleni, Faure, Louis, Olsen, Thale K., Otte, Jörg, Erickson, Alek, Semsch, Bettina, Andersson, Emma R., Ratz, Michael, Frisén, Jonas, Tischler, Arthur S., de Krijger, Ronald R., Bouderlique, Thibault, Akkuratova, Natalia, Vorontsova, Maria, Gusev, Oleg, Fried, Kaj, Sundström, Erik, Mei, Shenglin, Kogner, Per, Baryawno, Ninib, Kharchenko, Peter V., and Adameyko, Igor

Published
2021

25. FOXO1 and FOXO3 cooperatively regulate innate lymphoid cell development

Author

Luu, Thuy T., primary, Søndergaard, Jonas Nørskov, additional, Peña-Pérez, Lucía, additional, Kharazi, Shabnam, additional, Krstic, Aleksandra, additional, Meinke, Stephan, additional, Schmied, Laurent, additional, Frengen, Nicolai, additional, Heshmati, Yaser, additional, Kierczak, Marcin, additional, Bouderlique, Thibault, additional, Wagner, Arnika Kathleen, additional, Gustafsson, Charlotte, additional, Chambers, Benedict J., additional, Achour, Adnane, additional, Kutter, Claudia, additional, Höglund, Petter, additional, Månsson, Robert, additional, and Kadri, Nadir, additional

Published
2021
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26. A three-dimensional in vitro model of erythropoiesis recapitulates erythroid failure in myelodysplastic syndromes

Author

Elvarsdóttir, Edda María, primary, Mortera-Blanco, Teresa, additional, Dimitriou, Marios, additional, Bouderlique, Thibault, additional, Jansson, Monika, additional, Hofman, Isabel Juliana F., additional, Conte, Simona, additional, Karimi, Mohsen, additional, Sander, Birgitta, additional, Douagi, Iyadh, additional, Woll, Petter S., additional, and Hellström-Lindberg, Eva, additional

Published
2019
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27. The Concerted Action of E2-2 and HEB Is Critical for Early Lymphoid Specification

Author

Bouderlique, Thibault, primary, Peña-Pérez, Lucia, additional, Kharazi, Shabnam, additional, Hils, Miriam, additional, Li, Xiaoze, additional, Krstic, Aleksandra, additional, De Paepe, Ayla, additional, Schachtrup, Christian, additional, Gustafsson, Charlotte, additional, Holmberg, Dan, additional, Schachtrup, Kristina, additional, and Månsson, Robert, additional

Published
2019
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28. The concerted action of E2-2 and HEB is critical for early lymphoid specification

Author

Bouderlique, Thibault, primary, Perez, Lucia Peña, additional, Kharazi, Shabnam, additional, Hils, Miriam, additional, Li, Xiaoze, additional, Krstic, Aleksandra, additional, De Paepe, Ayla, additional, Schachtrup, Christian, additional, Gustafsson, Charlotte, additional, Holmberg, Dan, additional, Schachtrup, Kristina, additional, and Månsson, Robert, additional

Published
2018
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29. Superficial cells are self‐renewing chondrocyte progenitors, which form the articular cartilage in juvenile mice

Author

Li, Lei, primary, Newton, Phillip T., additional, Bouderlique, Thibault, additional, Sejnohova, Marie, additional, Zikmund, Tomas, additional, Kozhemyakina, Elena, additional, Xie, Meng, additional, Krivanek, Jan, additional, Kaiser, Jozef, additional, Qian, Hong, additional, Dyachuk, Vyacheslav, additional, Lassar, Andrew B., additional, Warman, Matthew L., additional, Barenius, Björn, additional, Adameyko, Igor, additional, and Chagin, Andrei S., additional

Published
2016
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33. Study of the osteoinductive and chondroinductive properties of the heparin affin regulatory peptide on human mesenchymal stromal cells, application in bone regeneration

Author

Bouderlique, Thibault, STAR, ABES, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Est, and Patricia Albanese

Subjects
Biomaterials, Réparation osseuse, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Ostéoblaste, Harp, Osteoblast, Bone repair, Biomatériaux, Cellules souches mesenchymateuses, Chondrocyte, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Mesenchymal stem cell
Abstract

Bone regeneration is a complicated process which involved many cellular types such as osteoblasts, chondrocytes and mesenchymal stromal cells (MSC). MSC can differentiate toward chondrocytes and osteoblasts, suggesting their implication in bone regeneration processes. Bone reparation involved a complex coordination of growth factors. Among them, heparin affin regulatory peptide (HARP) is found in callus during regeneration. However, its role is poorly understood. The aim of this thesis was (1) to evaluate HARP effects on proliferation, migration and differentiation of MSC in vitro, (2) to evaluate HARP ability to promote bone regeneration or bone formation.Our results demonstrate that HARP has chemoattractive and proliferative properties on human MSC. Moreover, we show for the first time that HARP commits human MSC toward hypertrophy during chondrogenesis. This is of great interest since hypertrophic chondrocytes are of primary importance in the late stage of endochondral bone formation. We further tested the association of HARP to scaffolds in a model of bone regeneration in femoral defect in rat. HARP associated scaffolds showed an invasion of cartilage and bony tissues, mimicking endochondral bone formation, whereas scaffold alone was just filled with fibrous tissue.During regenerative processes glycosaminoglycans, polysaccharides sulfated chains, are known as major components of the extracellular matrix and modulate the effects of growth factors during regenerative processes. Recently, structurally and functionally mimetics of GAG had been developed. During my PhD thesis, I was associated to the work of a doctoral student of P. Albanese who showed that GAG mimetics induce osteoblastic differentiation of MSC without any other osteoinductive treatment. The ectopic implantation of mimetic associated scaffolds didn't show effects on osteoformation but induced an enhancement of vascularization and of osteoclastic activity, both related to tissue remodeling. These results validate that GAG mimetics are of great interest in bone regenerative field.This study demonstrates for the first time the chondroinductive potential of HARP through its ability to induce cartilage specific matrix production by MSC in vitro but also by inducing cartilage tissue synthesis in vivo. The effects of HARP observed on bone regeneration, by inducing an endochondral bone formation similar to that observed in normal bone regeneration, confirm that HARP could be a good candidate in orthopedic surgery. Moreover, scaffold covalently linked with GAG mimetics should be tested in association with HARP. This strategy could increase the half life, control the release and potentiate HARP properties in vivo., La régénération osseuse est un processus impliquant de nombreux types cellulaires comme les ostéoblastes, les chondrocytes ou les cellules stromales mésenchymateuses (CSM). Les CSM possèdent des capacités de différenciation suggérant leur implication dans ce processus de réparation. La régénération osseuse est le fruit de la coordination complexe de l'activité de nombreux facteurs de croissance. Parmi eux, l'« Heparin affin regulatory peptide » (HARP) est fortement exprimé dans le callus durant la régénération mais son rôle n'est pas clairement établi. Le but de ce travail de thèse a été (1) d'évaluer les effets de HARP sur les propriétés de migration, de prolifération et de différenciation des CSM in vitro ; (2) évaluer la capacité de HARP à induire une formation osseuse ou une régénération osseuse in vivo.Nos résultats démontrent que HARP est chémoattractant pour les CSM et potentialise leur prolifération. De plus, nous montrons pour la première fois que le traitement de CSM par HARP durant leur chondroinduction conduit à une différenciation chondrocytaire de type hypertrophique. Ce type cellulaire est primordial dans les derniers stades de la formation osseuse endochondrale qui se met en place durant la croissance osseuse, mais également durant la réparation. L'implantation de biomatériaux associés à HARP dans un défaut osseux de condyle fémoral a conduit à la formation de cartilage et d'os dans l'implant, reproduisant le mécanisme physiologique de formation osseuse endochondrale. Le biomatériau seul n'a été envahi que par du tissu fibreux.Durant les processus de réparation tissulaire, les glycosaminoglycannes (GAG), des chaînes polysaccharidiques sulfatées, composants majeurs de la matrice extracellulaire, participent à la modulation des effets des facteurs de croissance durant la réparation. Récemment, des mimétiques structuraux et fonctionnels des GAG ont été développés. Durant ma thèse, j'ai été associé au travail d'un doctorant de l'équipe de P.Albanese, qui a montré que des mimétiques de GAG induisent une différenciation ostéoblastique des CSM en l'absence de traitement ostéoinducteur. L'implantation sous-cutanée de biomatériaux covalemment associés aux mimétiques ont également été menées, et ont permis d'observer des potentialisations des processus de vascularisation de l'implant et de l'activité ostéoclastique. Ces resultats ont permis de valider l'interêt des GAG mimétiques dans le cadre des thérapies de régénération osseuse.Cette étude démontre pour la première fois les effets chondroinducteurs directs de HARP sur la production de molécules de la matrice cartilagineuse par les CSM in vitro, mais également sur la synthèse de tissu cartilagineux in vivo. Les effets de HARP observés sur la régénération osseuse confirment qu'il pourrait être un bon candidat en chirurgie orthopédique en permettant une régénération de type endochondrale typique de la réparation physiologique. De plus les nouvelles stratégies developpées dans le laboratoire sur la fonctionnalisation covalente de biomateriaux par des GAG mimétiques, meriteraient d'etre testées en association avec HARP, afin d'augmenter sa demi-vie et de controler son relarguage et ses activités biologiques in vivo.

Published
2012

38. Author Correction: A previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiology.

Author

Petersen, Julian, Englmaier, Lukas, Artemov, Artem V., Poverennaya, Irina, Mahmoud, Ruba, Bouderlique, Thibault, Tesarova, Marketa, Deviatiiarov, Ruslan, Szilvásy-Szabó, Anett, Akkuratov, Evgeny E., Pajuelo Reguera, David, Zeberg, Hugo, Kaucka, Marketa, Kastriti, Maria Eleni, Krivanek, Jan, Radaszkiewicz, Tomasz, Gömöryová, Kristína, Knauth, Sarah, Potesil, David, and Zdrahal, Zbynek

Subjects
KIDNEY physiology, ENERGY metabolism, SCIENCE education, MEDICAL sciences
Abstract

The aforementioned affiliations have now been removed and the following was added for Prof. Oleg Gusev "Regulatory Genomics Research Center, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia". In addition, information was missing from the Funding section and has now been added to the acknowledgements section which reads "OG and RD were supported by Ministry of Science and Higher Education of the Russian Federation grant 075-15-2021-1344 and Japan Society for the Promotion of Science (JSPS) KAKENHI JP23H02226.". These errors have been corrected in both the PDF and HTML versions of the Article. [Extracted from the article]

Published
2023
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40. Glycosaminoglycan Mimetic Associated to Human Mesenchymal Stem Cell-Based Scaffolds Inhibit Ectopic Bone Formation, but Induce Angiogenesis In Vivo

Author

Frescaline, Guilhem, primary, Bouderlique, Thibault, additional, Mansoor, Leyya, additional, Carpentier, Gilles, additional, Baroukh, Brigitte, additional, Sineriz, Fernando, additional, Trouillas, Marina, additional, Saffar, Jean-Louis, additional, Courty, José, additional, Lataillade, Jean-Jacques, additional, Papy-Garcia, Dulce, additional, and Albanese, Patricia, additional

Published
2013
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42. Mesenchymal Stromal Cells, Instigator or Suppressor for the Development of MLL-AF9Induced Acute Myeloid Leukemia?

Author

Xiao, Pingnan, Heshmati, Yaser, Bouderlique, Thibault, Kondo, Makoto, Dolinska, Monika, Sandhow, Lakshmi, Johansson, Anne-Sofie, Walfridsson, Julian, and Qian, Hong

Abstract

It has been reported that bone marrow (BM) hematopoietic niche is critical for the maintenance of normal hematopoiesis and the development of hematopoietic disorders. However, little is known about how the different BM niche components contribute to the initiation and progression of acute myeloid leukemia (AML). To explore the role of BM stromal cells in the development of AML, we here characterized the BM stromal cells in AML mouse model induced by transplantation of mouse BM cellstransduced with MLL-AF9oncogene. We subdivided the BM stromal cells (CD45-TER119-) into mesenchymal stem cells (MSCs, CD31-CD44-CD51+SCA1+), mesenchymal progenitor cells (MPCs, CD31-CD44-CD51+SCA1-), and endothelial cells (CD31+) in the mice after development of AML by multicolor fluorescent activated cell sorting (FACS) (Qian et al., Mol Cell Biol, 2013). We found significantly increased frequencies of BM MSCs (p< 0.0001), MPCs (p< 0.0001), and endothelial cells (p< 0.0001) in the AML mice, indicating an AML-induced alteration of BM stromal cell composition. The increased frequency of MSCs in AML mouse BM was confirmed by the increased number of colony foming unit-fibroblasts in the AML mice (p< 0.0001). Furthermore, in vitromulti-lineage differentiation assay revealed increased adipogenic and osteogenic differentiation capacities of the BM MSCs in the AML mice. Consistent with the increased osteogenic differentiation capacity of AML MSCs, Runx2mRNA expression was increased in freshly sorted AML MSCs compared to that in the control mice. In addition, quantitative real time PCR on freshly sorted BM MPCs showed a dramatic downregulation of the genes important in hematopoietic stem cell regulation, including angiopoietin like 1 (Angptl1), C-X-C motif chemokine (Cxcl12), and kit ligand (Kitl)in the AML mice. The altered gene expression might contribute to the AML progression.

Published
2016
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