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2. A risk-reward examination of sample multiplexing reagents for single cell RNA-Seq

Author

Brown, Daniel V., Anttila, Casey J.A., Ling, Ling, Grave, Patrick, Baldwin, Tracey M., Munnings, Ryan, Farchione, Anthony J., Bryant, Vanessa L., Dunstone, Amelia, Biben, Christine, Taoudi, Samir, Weber, Tom S., Naik, Shalin H., Hadla, Anthony, Barker, Holly E., Vandenberg, Cassandra J., Dall, Genevieve, Scott, Clare L., Moore, Zachery, Whittle, James R., Freytag, Saskia, Best, Sarah A., Papenfuss, Anthony T., Olechnowicz, Sam W.Z., MacRaild, Sarah E., Wilcox, Stephen, Hickey, Peter F., Amann-Zalcenstein, Daniela, and Bowden, Rory

Published
2024
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5. Mesoderm-derived PDGFRA+ cells regulate the emergence of hematopoietic stem cells in the dorsal aorta

Author

Chandrakanthan, Vashe, Rorimpandey, Prunella, Zanini, Fabio, Chacon, Diego, Olivier, Jake, Joshi, Swapna, Kang, Young Chan, Knezevic, Kathy, Huang, Yizhou, Qiao, Qiao, Oliver, Rema A., Unnikrishnan, Ashwin, Carter, Daniel R., Lee, Brendan, Brownlee, Chris, Power, Carl, Brink, Robert, Mendez-Ferrer, Simon, Enikolopov, Grigori, Walsh, William, Göttgens, Berthold, Taoudi, Samir, Beck, Dominik, and Pimanda, John E.

Published
2022
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8. Clonal analysis of fetal hematopoietic stem/progenitor cell subsets reveals how post-transplantation capabilities are distributed

Author

Stonehouse, Olivia, primary, Biben, Christine, additional, Weber, Tom S, additional, Garnham, Alexandra, additional, Fennell, Katie, additional, Farley, Alison, additional, Terreaux, Antoine, additional, Alexander, Warren, additional, Dawson, Mark, additional, Naik, Shalin, additional, and Taoudi, Samir, additional

Published
2024
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9. GPIbα–filamin A interaction regulates megakaryocyte localization and budding during platelet biogenesis

Author

Ellis, Marc L., primary, Terreaux, Antoine, additional, Alwis, Imala, additional, Smythe, Rhyll, additional, Perdomo, Jose, additional, Eckly, Anita, additional, Cranmer, Susan L., additional, Passam, Freda H., additional, Maclean, Jessica, additional, Schoenwaelder, Simone M., additional, Ruggeri, Zaverio M., additional, Lanza, Francois, additional, Taoudi, Samir, additional, Yuan, Yuping, additional, and Jackson, Shaun P., additional

Published
2024
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10. A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics

Author

Amann-Zalcenstein, Daniela, Tian, Luyi, Schreuder, Jaring, Tomei, Sara, Lin, Dawn S., Fairfax, Kirsten A., Bolden, Jessica E., McKenzie, Mark D., Jarratt, Andrew, Hilton, Adrienne, Jackson, Jacob T., Di Rago, Ladina, McCormack, Matthew P., de Graaf, Carolyn A., Stonehouse, Olivia, Taoudi, Samir, Alexander, Warren S., Nutt, Stephen L., Ritchie, Matthew E., Ng, Ashley P., and Naik, Shalin H.

Published
2020
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11. Emergence and expansion of embryonic definitive haematopoietic stem cells

Author

Taoudi, Samir

Subjects
611
Abstract

De novo generation and physiological expansion of definitive haematopoietic stem cells (dHSCs) occurs exclusively during embryogenesis and is initiated within the dorsal aorta/para-aortic mesenchyme (Ao) of the E11.5 aorta-gonad-mesonephros (AGM) region. The elucidation of the in vivo induction of dHSC emergence and regulation of expansion is likely to be a preparation to the success of generating dHSC in vitro and facilitating an effective and robust expansion of pre-existing dHSCs, thus providing a basis for potentially useful therapeutic translation. Utilising flow cytometry and the in vivo long-term haematopoietic reconstitution assays, we describe the endothelial affiliation of early dHSC as they emerge within the embryonic AGM region and yolk sac, fundamentally defined by a VE-cadherin +CD45+ immunophenotype, and the successive restriction to a haematopoietic identity upon hepatic colonisation. Well-defined haematopoietic colony forming unit-culture (CFU-C) and endothelial network forming assays were used to reveal that the early strong endothelio-haematopoietic promiscuity observed in the early embryo is lost in favour of a mutually exclusive lineage commitment. Experiments using a novel liquid suspension culture system reveal that successful in vitro myeloid differentiation of VE-cadherin +CD45+dHSCs/multipotent haematopoietic progenitors from the E11.5 AGM region is dependent on an interaction with the endothelial compartment. To directly test the predominating hypothesis of a dorso-ventral polarity in haematopoietic activity of the AGM region I have bisected the Ao from the E11.5 AGM region along the dorso-ventral axis and subjected the resultant ventral (AoV) and dorsal (AoD) aspects to in vivo and in vitro tests. Here I provide the first functional data to support the hypothesis of an anatomical polarity of dHSC distribution. Furthermore, I provide evidence to support an hypothesis that in vivo components of the E10.5-11.5 Ao only permit ventral emergence and expansion of dHSCs. Investigation into the transcriptional activity of the E11.5 AoV and AoD highlight the differential expression of GATA2, GATA3, HoxB4, Runxl, BMP4, Noggin and Chordin. These data demonstrate the conductive nature of the AGM region, which after structural disruption not only supports the ex vivo maintenance of dHSC activity but also exhibits a marked capacity for rapid stem cell expansion. Thus, in our hands we have a powerful system with the potential to allow useful investigation into the fundamental processes that occupy the field of stem cell biology; the mechanisms of stem cell emergence, induction and expansion.

Published
2006

14. 3006 – IN VIVO CLONAL TRACKING REVEALS EVIDENCE OF HAEMANGIOBLAST AND HAEMATOMESOBLAST CONTRIBUTION TO YOLK SAC HAEMATOPOIESIS

Author

Biben, Christine, primary, Weber, Tom, additional, Potts, Kathy, additional, Choi, Jarny, additional, Miles, Denise, additional, Carmagnac, Amandine, additional, Sargent, Tobias, additional, de Graaf, Carolyn, additional, Fennell, Katie, additional, Farley, Alison, additional, Stonehouse, Olivia, additional, Dawson, Mark, additional, Hilton, Douglas, additional, Naik, Shalin, additional, and Taoudi, Samir, additional

Published
2023
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19. Vaccine‐induced immune thrombosis and thrombocytopenia syndrome following adenovirus‐vectored severe acute respiratory syndrome coronavirus 2 vaccination: a novel hypothesis regarding mechanisms and implications for future vaccine development

Author

Monagle, Paul, primary, Ng, Ashley P, additional, Linden, Matthew, additional, Ignjatovic, Vera, additional, Farley, Alison, additional, Taoudi, Samir, additional, Pasricha, Sant Rayn, additional, and Torresi, Joseph, additional

Published
2021
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21. Mesoderm-Derived PDGFRA+Cells Regulate the Emergence of Hematopoietic Stem Cells in the Dorsal Aorta

Author

Chandrakanthan, Vashe, primary, Rorimpandey, Prunella, additional, Zanini, Fabio, additional, Chacon, Diego, additional, Kang, Young Chan, additional, Knezevic, Kathy, additional, Huang, Yizhou, additional, Qiao, Qiao, additional, Oliver, Rema A., additional, Unnikrishnan, Ashwin, additional, Carter, Daniel R., additional, Lee, Brendan, additional, Brownlee, Chris, additional, Power, Carl, additional, Mendez-Ferrer, Simon, additional, Enikolopov, Grigori, additional, Walsh, William, additional, Göttgens, Berthold, additional, Taoudi, Samir, additional, Beck, Dominik, additional, and Pimanda, John E., additional

Published
2021
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22. 2017 – THE MESODERMAL LINEAGES OF THE YOLK SAC ARE SEEDED BY HAEMANGIOBLAST, HAEMATOMESOBLAST, AND MESENCHYMOANGIOBLAST PRECURSORS

Author

Biben, Christine, primary, Weber, Tom, additional, Potts, Kathryn, additional, Choi, Jarny, additional, Miles, Denise, additional, Carmagnac, Amandine, additional, Sargent, Tobias, additional, de Graaf, Carolyn, additional, Fennell, Katie, additional, Farley, Alison, additional, Stonehouse, Olivia, additional, Dawson, Mark, additional, Hilton, Douglas, additional, Naik, Shalin, additional, and Taoudi, Samir, additional

Published
2021
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26. A Prox1enhancer represses haematopoiesis in the lymphatic vasculature

Author

Kazenwadel, Jan, Venugopal, Parvathy, Oszmiana, Anna, Toubia, John, Arriola-Martinez, Luis, Panara, Virginia, Piltz, Sandra G., Brown, Chris, Ma, Wanshu, Schreiber, Andreas W., Koltowska, Katarzyna, Taoudi, Samir, Thomas, Paul Q., Scott, Hamish S., and Harvey, Natasha L.

Abstract

Transcriptional enhancer elements are responsible for orchestrating the temporal and spatial control over gene expression that is crucial for programming cell identity during development1–3. Here we describe a novel enhancer element that is important for regulating the expression of Prox1in lymphatic endothelial cells. This evolutionarily conserved enhancer is bound by key lymphatic transcriptional regulators including GATA2, FOXC2, NFATC1 and PROX1. Genome editing of the enhancer to remove five nucleotides encompassing the GATA2-binding site resulted in perinatal death of homozygous mutant mice due to profound lymphatic vascular defects. Lymphatic endothelial cells in enhancer mutant mice exhibited reduced expression of genes characteristic of lymphatic endothelial cell identity and increased expression of genes characteristic of haemogenic endothelium, and acquired the capacity to generate haematopoietic cells. These data not only reveal a transcriptional enhancer element important for regulating Prox1expression and lymphatic endothelial cell identity but also demonstrate that the lymphatic endothelium has haemogenic capacity, ordinarily repressed by Prox1.

Published
2023
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28. Membrane budding is a major mechanism of in vivo platelet biogenesis

Author

Potts, Kathryn S., primary, Farley, Alison, additional, Dawson, Caleb A., additional, Rimes, Joel, additional, Biben, Christine, additional, de Graaf, Carolyn, additional, Potts, Margaret A., additional, Stonehouse, Olivia J., additional, Carmagnac, Amandine, additional, Gangatirkar, Pradnya, additional, Josefsson, Emma C., additional, Anttila, Casey, additional, Amann-Zalcenstein, Daniela, additional, Naik, Shalin, additional, Alexander, Warren S., additional, Hilton, Douglas J., additional, Hawkins, Edwin D., additional, and Taoudi, Samir, additional

Published
2020
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29. The clonal and molecular aetiology of emergency dendritic cell development

Author

Lin, Dawn S., primary, Tian, Luyi, additional, Tomei, Sara, additional, Amann-Zalcenstein, Daniela, additional, Baldwin, Tracey M., additional, Weber, Tom S., additional, Schreuder, Jaring, additional, Stonehouse, Olivia, additional, Rautela, Jai, additional, Huntington, Nicholas D., additional, Ng, Ashley P., additional, Nutt, Stephen L., additional, Taoudi, Samir, additional, Ritchie, Matthew E., additional, Hodgkin, Philip D., additional, and Naik, Shalin H., additional

Published
2020
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30. Mesoderm-derived PDGFRA+cells regulate the emergence of hematopoietic stem cells in the dorsal aorta

Author

Chandrakanthan, Vashe, Rorimpandey, Prunella, Zanini, Fabio, Chacon, Diego, Olivier, Jake, Joshi, Swapna, Kang, Young Chan, Knezevic, Kathy, Huang, Yizhou, Qiao, Qiao, Oliver, Rema A., Unnikrishnan, Ashwin, Carter, Daniel R., Lee, Brendan, Brownlee, Chris, Power, Carl, Brink, Robert, Mendez-Ferrer, Simon, Enikolopov, Grigori, Walsh, William, Göttgens, Berthold, Taoudi, Samir, Beck, Dominik, and Pimanda, John E.

Abstract

Mouse haematopoietic stem cells (HSCs) first emerge at embryonic day 10.5 (E10.5), on the ventral surface of the dorsal aorta, by endothelial-to-haematopoietic transition. We investigated whether mesenchymal stem cells, which provide an essential niche for long-term HSCs (LT-HSCs) in the bone marrow, reside in the aorta–gonad–mesonephros and contribute to the development of the dorsal aorta and endothelial-to-haematopoietic transition. Here we show that mesoderm-derived PDGFRA+stromal cells (Mesp1derPSCs) contribute to the haemogenic endothelium of the dorsal aorta and populate the E10.5–E11.5 aorta–gonad–mesonephros but by E13.5 were replaced by neural-crest-derived PSCs (Wnt1derPSCs). Co-aggregating non-haemogenic endothelial cells with Mesp1derPSCs but not Wnt1derPSCs resulted in activation of a haematopoietic transcriptional programme in endothelial cells and generation of LT-HSCs. Dose-dependent inhibition of PDGFRA or BMP, WNT and NOTCH signalling interrupted this reprogramming event. Together, aorta–gonad–mesonephros Mesp1derPSCs could potentially be harnessed to manufacture LT-HSCs from endothelium.

Published
2022
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31. Analysis of the Spatiotemporal Development of Hematopoietic Stem and Progenitor Cells in the Early Human Embryo

Author

Easterbrook, Jennifer, Rybtsov, Stanislav, Gordon-Keylock, Sabrina, Ivanovs, Andrejs, Taoudi, Samir, Anderson, Richard, and Medvinsky, Alexander

Subjects
Mice, SCID, Article, Colony-Forming Units Assay, Spatio-Temporal Analysis, Mice, Inbred NOD, Animals, Humans, hematopoietic progenitors, Gonads, lcsh:QH301-705.5, Aorta, Cells, Cultured, Cell Proliferation, Mice, Knockout, yolk sac, lcsh:R5-920, Stem Cells, Hematopoietic Stem Cell Transplantation, hemic and immune systems, Embryo, Mammalian, Hematopoietic Stem Cells, human embryo, hematopoietic stem cells, Hematopoiesis, lcsh:Biology (General), Heterografts, lcsh:Medicine (General), fetal liver, Interleukin Receptor Common gamma Subunit
Abstract

Summary: Definitive hematopoietic stem cells (HSCs) first emerge in the aorta-gonad-mesonephros (AGM) region in both mice and humans. An ex vivo culture approach has enabled recapitulation and analysis of murine HSC development. Knowledge of early human HSC development is hampered by scarcity of tissue: analysis of both CFU-C and HSC development in the human embryo is limited. Here, we characterized the spatial distribution and temporal kinetics of CFU-C development within early human embryonic tissues. We then sought to adapt the murine ex vivo culture system to recapitulate human HSC development. We show robust expansion of CFU-Cs and maintenance, but no significant expansion, of human HSCs in culture. Furthermore, we demonstrate that HSCs emerge predominantly in the middle section of the dorsal aorta in our culture system. We conclude that there are important differences between early mouse and human hematopoiesis, which currently hinder the quest to recapitulate human HSC development ex vivo. : Knowledge of human HSC development will be essential for directing the successful generation of HSCs in vitro. Medvinsky and colleagues characterize the spatiotemporal development of CFU-Cs in the human embryo. Using an ex vivo culture system, they show robust expansion of CFU-Cs, maintenance of HSCs, and demonstrate that HSCs emerge predominantly in the middle section of the dorsal aorta. Keywords: hematopoietic stem cells, hematopoietic progenitors, human embryo, yolk sac, fetal liver

Published
2019

35. Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult hematopoietic stem cells

Author

Souilhol, Céline, Gonneau, Christèle, Lendinez, Javier G., Batsivari, Antoniana, Rybtsov, Stanislav, Wilson, Heather, Morgado-Palacin, Lucia, Hills, David, Taoudi, Samir, Antonchuk, Jennifer, Zhao, Suling, and Medvinsky, Alexander

Subjects
Male, Science, Hematopoietic Stem Cell Transplantation, Bone Morphogenetic Protein 4, Hematopoietic Stem Cells, Article, Mice, Inbred C57BL, Mesonephros, embryonic structures, Animals, Female, Hedgehog Proteins, Gonads, Aorta, Signal Transduction
Abstract

During embryonic development, adult haematopoietic stem cells (HSCs) emerge preferentially in the ventral domain of the aorta in the aorta–gonad–mesonephros (AGM) region. Several signalling pathways such as Notch, Wnt, Shh and RA are implicated in this process, yet how these interact to regulate the emergence of HSCs has not previously been described in mammals. Using a combination of ex vivo and in vivo approaches, we report here that stage-specific reciprocal dorso–ventral inductive interactions and lateral input from the urogenital ridges are required to drive HSC development in the aorta. Our study strongly suggests that these inductive interactions in the AGM region are mediated by the interplay between spatially polarized signalling pathways. Specifically, Shh produced in the dorsal region of the AGM, stem cell factor in the ventral and lateral regions, and BMP inhibitory signals in the ventral tissue are integral parts of the regulatory system involved in the development of HSCs., It is unclear how the microenvironment of the aorta-gonad-mesonephros influences haematopoietic stem cell (HSC) production early in mouse development. Here, Souilhol et al. use an in vitro aggregate system as a tool to understand how several pathways, BMP, SCF and Shh, may regulate HSC production.

Published
2016

36. A new lymphoid-primed progenitor marked by Dach1downregulation identified with single cell multi-omics

Author

Amann-Zalcenstein, Daniela, Tian, Luyi, Schreuder, Jaring, Tomei, Sara, Lin, Dawn S., Fairfax, Kirsten A., Bolden, Jessica E., McKenzie, Mark D., Jarratt, Andrew, Hilton, Adrienne, Jackson, Jacob T., Di Rago, Ladina, McCormack, Matthew P., de Graaf, Carolyn A., Stonehouse, Olivia, Taoudi, Samir, Alexander, Warren S., Nutt, Stephen L., Ritchie, Matthew E., Ng, Ashley P., and Naik, Shalin H.

Abstract

A classical view of blood cell development is that multipotent hematopoietic stem and progenitor cells (HSPCs) become lineage-restricted at defined stages. Lin-c-Kit+Sca-1+Flt3+cells, termed lymphoid-primed multipotent progenitors (LMPPs), have lost megakaryocyte and erythroid potential but are heterogeneous in their fate. Here, through single-cell RNA sequencing, we identify the expression of Dach1and associated genes in this fraction as being coexpressed with myeloid/stem genes but inversely correlated with lymphoid genes. Through generation of Dach1–GFP reporter mice, we identify a transcriptionally and functionally unique Dach1–GFP-subpopulation within LMPPs with lymphoid potential with low to negligible classic myeloid potential. We term these ‘lymphoid-primed progenitors’ (LPPs). These findings define an early definitive branch point of lymphoid development in hematopoiesis and a means for prospective isolation of LPPs.

Published
2020
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37. Declined presentation mesenchymal stem cell-like cell mediated hematopoietic stem cell generation from non-hemogenic endothelial cells

Author

Chandrakanthan, Vashe, primary, Chan Kang, Young, additional, Knezevic, Kathy, additional, Qiao, Qiao, additional, Oliver, Rema, additional, Unnikrishnan, Ashwin, additional, Huang, Yizhou, additional, Walsh, William, additional, Lee, Brendan, additional, Lee, Chris Brown, additional, Power, Carl, additional, Beck, Dominik, additional, Taoudi, Samir, additional, and Pimanda, John, additional

Published
2017
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39. Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult haematopoietic stem cells

Author

Souilhol, Céline, primary, Gonneau, Christèle, additional, Lendinez, Javier G., additional, Batsivari, Antoniana, additional, Rybtsov, Stanislav, additional, Wilson, Heather, additional, Morgado-Palacin, Lucia, additional, Hills, David, additional, Taoudi, Samir, additional, Antonchuk, Jennifer, additional, Zhao, Suling, additional, and Medvinsky, Alexander, additional

Published
2016
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42. Identification of diploid platelet-forming cells prior to the emergence of polyploidy megakaryocyte in the mouse embryo

Author

Potts, Kathryn, primary, Sargeant, Tobias, additional, Markham, John, additional, Shi, Wei, additional, Dawson, Caleb, additional, Josefsson, Emma, additional, Liakhovitskaia, Anna, additional, Smyth, Gordon, additional, Kile, Benjamin, additional, Medvinsky, Alexander, additional, Alexander, Warren, additional, Hilton, Douglas, additional, and Taoudi, Samir, additional

Published
2014
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48. ERG dependence distinguishes developmental control of hematopoietic stem cell maintenance from hematopoietic specification

Author

Taoudi, Samir, primary, Bee, Thomas, additional, Hilton, Adrienne, additional, Knezevic, Kathy, additional, Scott, Julie, additional, Willson, Tracy A., additional, Collin, Caitlin, additional, Thomas, Tim, additional, Voss, Anne K., additional, Kile, Benjamin T., additional, Alexander, Warren S., additional, Pimanda, John E., additional, and Hilton, Douglas J., additional

Published
2011
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