A5086295699- Zebrafish Biomedical Research Applications
- Hematopoietic Stem Cell Transplantation
- Platelet Disorders and Treatments
- Blood groups and transfusion
- Neonatal Respiratory Health Research
- Single-cell and spatial transcriptomics
- Pluripotent Stem Cells Research
- Prenatal Screening and Diagnostics
- Immune cells in cancer
- T-cell and B-cell Immunology
- Renal Diseases and Glomerulopathies
- Immune Cell Function and Interaction
- Renal and related cancers
- Pregnancy and preeclampsia studies
- Blood properties and coagulation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Inorganic Fluorides and Related Compounds
- Immunotherapy and Immune Responses
- Polyoxometalates: Synthesis and Applications
- Phagocytosis and Immune Regulation
- Lipid metabolism and disorders
- Acute Myeloid Leukemia Research
- Congenital heart defects research
- Extracellular vesicles in disease
- Heparin-Induced Thrombocytopenia and Thrombosis
The University of Melbourne
2013-2024
Walter and Eliza Hall Institute of Medical Research
2015-2024
University of Bristol
2024
University of Edinburgh
2005-2010
MRC Centre for Regenerative Medicine
2009-2010
Medical Research Council
2007
Harvard University
2007
Juvenile Diabetes Research Foundation
2007
The aorta-gonad-mesonephros region plays an important role in hematopoietic stem cell (HSC) development during mouse embryogenesis. vascular endothelial cadherin⁺ CD45⁺ (VE-cad⁺CD45⁺) population contains the major type of immature pre-HSCs capable developing into long-term repopulating definitive HSCs. In this study, we developed a new coaggregation culture system, which supports maturation novel CD45-negative (VE-cad⁺CD45⁻CD41⁺) appearance these precedes VE-cad⁺CD45⁺ (termed here I and II...
The first definitive/adult-type hematopoietic stem cells (HSCs) in the mouse aorta-gonad-mesonephros region emerge between embryonic days 10.5 and 11.5. discovery of clusters on ventral luminal surface dorsal aorta various vertebrate species has led to speculation that floor may play an essential role for development definitive system. Here, we functionally show affiliation HSCs with aorta, whereas colony-forming activity is associated both domains. We a rare population PECAM1(high)CD45(+)...
During embryonic development, adult haematopoietic stem cells (HSCs) emerge preferentially in the ventral domain of aorta aorta-gonad-mesonephros (AGM) region. Several signalling pathways such as Notch, Wnt, Shh and RA are implicated this process, yet how these interact to regulate emergence HSCs has not previously been described mammals. Using a combination ex vivo approaches, we report here that stage-specific reciprocal dorso-ventral inductive interactions lateral input from urogenital...
Abstract During embryogenesis, haematopoietic and endothelial lineages emerge closely in time space. It is thought that the first blood endothelium derive from a common clonal ancestor, haemangioblast. However, investigation of candidate haemangioblasts vitro revealed capacity for mesenchymal differentiation, feature more compatible with an earlier mesodermal precursor. To date, no evidence vivo haemangioblast has been discovered. Using single cell RNA-Sequencing cellular barcoding, we have...
Single-cell RNA sequencing (scRNA-Seq) has emerged as a powerful tool for understanding cellular heterogeneity and function. However the choice of sample multiplexing reagents can impact data quality experimental outcomes. In this study, we compared various reagents, including MULTI-Seq, Hashtag antibody, CellPlex, across diverse types such human peripheral blood mononuclear cells (PBMCs), mouse embryonic brain patient-derived xenografts (PDXs). We found that all worked well in cell robust...
The yolk sac and the para-aortic splanchnopleura/aorta-genital ridges-mesonephros (P-Sp/AGM) region are main sites of haematopoietic activity in mouse embryo at pre-liver stage development. By day 11.5 gestation, AGM is capable autonomous initiation expansion definitive stem cells (HSCs). 12.5, HSC reduced whilst a second wave HSCs begins to emerge sac. We show here that emerging both locations marked by co-expression endothelial-specific marker VE-cadherin pan-leukocyte antigen CD45....
Although many genes are known to be critical for early hematopoiesis in the embryo, it remains unclear whether distinct regulatory pathways exist control hematopoietic specification versus stem cell (HSC) emergence and function. Due their interaction with key regulators of commitment, particular interest has focused on role ETS family transcription factors; these, ERG is predicted play an important initiation hematopoiesis, yet we do not know if or when required. Using vitro vivo models HSC...
How platelets are produced by megakaryocytes in vivo remains controversial despite more than a century of investigation. Megakaryocytes readily produce proplatelet structures vitro; however, visualization platelet release from proplatelets has remained elusive. We show that within the native prenatal and adult environments, frequency rate formation is incompatible with physiological demands replacement. resolve this inconsistency performing in-depth analysis plasma membrane budding, cellular...
Abstract Mouse haematopoietic stem cells (HSCs) first emerge at embryonic day 10.5 (E10.5), on the ventral surface of dorsal aorta, by endothelial-to-haematopoietic transition. We investigated whether mesenchymal cells, which provide an essential niche for long-term HSCs (LT-HSCs) in bone marrow, reside aorta–gonad–mesonephros and contribute to development aorta Here we show that mesoderm-derived PDGFRA + stromal ( Mesp1 der PSCs) haemogenic endothelium populate E10.5–E11.5 but E13.5 were...
It has been proposed that adult haematopoiesis is sustained by multipotent progenitor (MPP) clones are specified during development. From an immunophenotypic perspective, it known hematopoietic stem cell (HSC) and MPPs present in the fetal liver yet our understanding of how functionally compare to those bone marrow incomplete. Using acute-term transplantations, we found at a population-level MPP classes exhibited similar lineage biases as cells, albeit with some difference lymphoid output....
Hematopoietic development begins in several locations the mammalian embryo: yolk sac, aorta-gonad-mesonephros region (AGM), and chorio-allantoic placenta. Generation of most potent cells, adult definitive hematopoietic stem cells (HSCs), occurs within body mouse embryo at midgestation AGM region. Similarly, equivalent developmental time human embryo, has been shown to contain multipotent progenitors. Hence, serves as an excellent model study development. To further studies on ontogeny...
The E11.5 aorta-gonad-mesonephros (AGM) region is a site of hematopoietic stem cell (HSC) development prior to colonisation the embryonic liver. generation HSCs in embryo starting from E11 very rapid. Here, we have assessed AGM during at precise somitic ages. Although numbers committed precursors fluctuate throughout day, repopulation activity noticeably increases mid (44 s.p.) end (48 day 11 gestation. While two thirds regions contain no definitive HSCs, shortly liver colonisation, all...
Abstract Cellular reaggregation methods have been used to generate in vitro organotypic cultures as a means elucidate the cellular and molecular requirements of organogenesis. However, reproducibility from experiment has remained problematic furthermore, current protocols do not support many important tissues. Here, using thymus model organ, we present novel method termed “compaction reaggregation” that offers improved kinetics greatly efficiency. Using compaction able reaggregate...
Abstract Much remains to be learned about the clonal fate of mammalian epiblast cells in vivo . Here we develop a high diversity, throughput, Cre recombinase-driven DNA LoxCode barcoding technology for lineage tracing. E5.5 pre-gastrulation embryos were barcoded utero and clones later assessed their contribution wide range tissues cell types E12.5 organogenesis-stage embryo. While few contributed broadly most three germ layers, many biased towards either blood, ectoderm lineages, mesenchymal...
We hypothesize that thrombosis with thrombocytopenia syndrome recently described after administration of adenovirus-vectored vaccines for severe acute respiratory coronavirus 2 (SARS-CoV-2) occurs as a result the unique properties adenovirus vectors, which can have widespread biodistribution throughout body. The antigen is delivered to megakaryocyte cells, act part primary immune system and distribute within progeny platelets, also key component system. interaction induces preformed...
Single-cell RNA sequencing (scRNA-Seq) has emerged as a powerful tool for understanding cellular heterogeneity and function. However the choice of sample multiplexing reagents can impact data quality experimental outcomes. In this study, we compared various reagents, including MULTI-Seq, Hashtag antibody, CellPlex, across diverse types such human peripheral blood mononuclear cells (PBMCs), mouse embryonic brain patient-derived xenografts (PDXs). We found that all worked well in cell robust...