scholarly journals Adult zebrafish Langerhans cells arise from hematopoietic stem/progenitor cells

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Sicong He ◽  
Jiahao Chen ◽  
Yunyun Jiang ◽  
Yi Wu ◽  
Lu Zhu ◽  
...  
Keyword(s):  
Langerhans Cells ◽  
Lineage Tracing ◽  
Cell Labeling ◽  
Adult Zebrafish ◽  
Hematopoietic Stem ◽  
Mouse Aorta ◽  
Labeling Method ◽  
The Brain ◽  
Ventral Wall ◽  
Skin Epidermis

The origin of Langerhans cells (LCs), which are skin epidermis-resident macrophages, remains unclear. Current lineage tracing of LCs largely relies on the promoter-Cre-LoxP system, which often gives rise to contradictory conclusions with different promoters. Thus, reinvestigation with an improved tracing method is necessary. Here, using a laser-mediated temporal-spatial resolved cell labeling method, we demonstrated that most adult LCs originated from the ventral wall of the dorsal aorta (VDA), an equivalent to the mouse aorta, gonads, and mesonephros (AGM), where both hematopoietic stem cells (HSCs) and non-HSC progenitors are generated. Further fine-fate mapping analysis revealed that the appearance of LCs in adult zebrafish was correlated with the development of HSCs, but not T cell progenitors. Finally, we showed that the appearance of tissue-resident macrophages in the brain, liver, heart, and gut of adult zebrafish was also correlated with HSCs. Thus, the results of our study challenged the EMP-origin theory for LCs.

scholarly journals Identification and characterization of a non-conventional CD45 negative perivascular macrophage population within the mouse brain.

2021 ◽  
Author(s):  
Carole Siret ◽  
Max van Lessen ◽  
Hyun-Woo Jeong ◽  
Shuaiwei Wang ◽  
Milesa Simic ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Lineage Tracing ◽  
Cerebral Vasculature ◽  
Hematopoietic Stem ◽  
Macrophage Population ◽  
Perivascular Macrophages ◽  
Similar Location ◽  
The Brain ◽  
Identification And Characterization

Abstract Perivascular macrophages (pvM) are closely associated with cerebral vasculature and play an essential role in drainage of the brain and regulation of the immune response. Here, using reporter mouse models and immunofluorescence on sections and whole brain, flow cytometry and single cell sequencing, we identify a Lyve1+ brain perivascular population lacking classical macrophage markers such as CD45 and Cx3cr1. We named the new non-conventional CD45 negative perivascular macrophages pvM2. These cells have a similar location, morphology and phagocytic function as conventional pvM. The pvM2 are not derived from hematopoietic stem cells, as they are negative in the VavtdT lineage tracing model. They increase in number after photothrombotic induced stroke established by flow cytometry and 3D immunofluorescence analysis. Since CD45 negative cells were typically excluded from macrophage studies, the presence of pvM2 has been previously missed and their role is of importance to assess in the brain disease models.

scholarly journals Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell transcriptomics

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lars Velten ◽  
Benjamin A. Story ◽  
Pablo Hernández-Malmierca ◽  
Simon Raffel ◽  
Daniel R. Leonce ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Single Cell ◽  
Lineage Tracing ◽  
Specific Gene ◽  
Leukemic Stem Cells ◽  
Hematopoietic Stem ◽  
Mutational Status

AbstractCancer stem cells drive disease progression and relapse in many types of cancer. Despite this, a thorough characterization of these cells remains elusive and with it the ability to eradicate cancer at its source. In acute myeloid leukemia (AML), leukemic stem cells (LSCs) underlie mortality but are difficult to isolate due to their low abundance and high similarity to healthy hematopoietic stem cells (HSCs). Here, we demonstrate that LSCs, HSCs, and pre-leukemic stem cells can be identified and molecularly profiled by combining single-cell transcriptomics with lineage tracing using both nuclear and mitochondrial somatic variants. While mutational status discriminates between healthy and cancerous cells, gene expression distinguishes stem cells and progenitor cell populations. Our approach enables the identification of LSC-specific gene expression programs and the characterization of differentiation blocks induced by leukemic mutations. Taken together, we demonstrate the power of single-cell multi-omic approaches in characterizing cancer stem cells.

Exposure to aluminium causes behavioural alterations and oxidative stress in the brain of adult zebrafish

2021 ◽  
Vol 85 ◽  
pp. 103636
Author(s):  
Teresa Capriello ◽  
Luis M. Félix ◽  
Sandra M. Monteiro ◽  
Dércia Santos ◽  
Rita Cofone ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Adult Zebrafish ◽  
The Brain ◽  
And Oxidative Stress

Protective effect of Saccharomyces cerevisiae in Rattus norvegicus Ischemic Stroke Model

2021 ◽  
pp. 5785-5789
Author(s):  
Dedy Budi Kurniawan ◽  
Mokhamad Fahmi Rizki Syaban ◽  
Arinal Mufidah ◽  
Muhammad Unzila Rafsi Zulfikri ◽  
Wibi Riawan
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Ischemic Stroke ◽  
Brain Tissue ◽  
Tissue Injury ◽  
Intervention Group ◽  
Positive Control ◽  
Positive Control Group ◽  
Control Group ◽  
Hematopoietic Stem ◽  
The Brain

Stroke is one of the leading causes of morbidity and mortality in all ages. Ischemic stroke activates excitotoxic glutamate cascade leading to brain tissue injury. Saccharomyces cerevisiae is a unicellular yeast widely found in nature. S. cerevisiae is neuroprotective and able to increase the differentiation of hematopoietic stem cells (HSCs) into neuronal cells. it may increase levels of neuroprotectant BDNF in the brain tissue, therefore increase the protection of neurons. BDNF may prevent glutamate-driven excitotoxicity by reducing glutamate levels. This study uses a randomized post-test only controlled group design. In this in vivo study, rodent models of ischemic stroke were divided into five groups comprising of the negative control group, positive control group, intervention group 1 (18mg/kgBW), intervention group 2 (36mg/kgBW) and intervention group 3 (72 mg/kgBW). Groups treated with Saccharomyces cerevisiae extract showed significantly increased BDNF levels in the brain tissue, and the expression of the glutamate level was significantly reduced (P <0.05) compared to the positive control group. Thus Saccharomyces cerevisiae has a promising potential to become a therapy against ischemic stroke disease. however further research is needed regarding the efficacy and toxicity of Saccharomyces cerevisiae.

scholarly journals Epidermal γδ T cells originate from yolk sac hematopoiesis and clonally self-renew in the adult

2018 ◽  
Vol 215 (12) ◽  
pp. 2994-3005 ◽  
Author(s):  
Rebecca Gentek ◽  
Clément Ghigo ◽  
Guillaume Hoeffel ◽  
Audrey Jorquera ◽  
Rasha Msallam ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cell ◽  
Fetal Liver ◽  
Γδ T Cells ◽  
Yolk Sac ◽  
Lineage Tracing ◽  
Hematopoietic Stem ◽  
Turn Over ◽  
Initial Seeding ◽  
Mapping Systems

The murine epidermis harbors two immune cell lineages, Langerhans cells (LCs) and γδ T cells known as dendritic epidermal T cells (DETCs). LCs develop from both early yolk sac (YS) progenitors and fetal liver monocytes before locally self-renewing in the adult. For DETCs, the mechanisms of homeostatic maintenance and their hematopoietic origin are largely unknown. Here, we exploited multicolor fate mapping systems to reveal that DETCs slowly turn over at steady state. Like for LCs, homeostatic maintenance of DETCs is achieved by clonal expansion of tissue-resident cells assembled in proliferative units. The same mechanism, albeit accelerated, facilitates DETC replenishment upon injury. Hematopoietic lineage tracing uncovered that DETCs are established independently of definitive hematopoietic stem cells and instead originate from YS hematopoiesis, again reminiscent of LCs. DETCs thus resemble LCs concerning their maintenance, replenishment mechanisms, and hematopoietic development, suggesting that the epidermal microenvironment exerts a lineage-independent influence on the initial seeding and homeostatic maintenance of its resident immune cells.

scholarly journals Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing

2017 ◽  
Vol 214 (10) ◽  
pp. 2875-2887 ◽  
Author(s):  
Qin Tang ◽  
Sowmya Iyer ◽  
Riadh Lobbardi ◽  
John C. Moore ◽  
Huidong Chen ◽  
...  
Keyword(s):  
Single Cell ◽  
Natural Killer ◽  
Progenitor Cells ◽  
Rna Sequencing ◽  
Immune Cell ◽  
Interleukin 2 ◽  
Kidney Cells ◽  
Cell Heterogeneity ◽  
Adult Zebrafish ◽  
Hematopoietic Stem

Recent advances in single-cell, transcriptomic profiling have provided unprecedented access to investigate cell heterogeneity during tissue and organ development. In this study, we used massively parallel, single-cell RNA sequencing to define cell heterogeneity within the zebrafish kidney marrow, constructing a comprehensive molecular atlas of definitive hematopoiesis and functionally distinct renal cells found in adult zebrafish. Because our method analyzed blood and kidney cells in an unbiased manner, our approach was useful in characterizing immune-cell deficiencies within DNA–protein kinase catalytic subunit (prkdc), interleukin-2 receptor γ a (il2rga), and double-homozygous–mutant fish, identifying blood cell losses in T, B, and natural killer cells within specific genetic mutants. Our analysis also uncovered novel cell types, including two classes of natural killer immune cells, classically defined and erythroid-primed hematopoietic stem and progenitor cells, mucin-secreting kidney cells, and kidney stem/progenitor cells. In total, our work provides the first, comprehensive, single-cell, transcriptomic analysis of kidney and marrow cells in the adult zebrafish.

scholarly journals Hlf Expression Marks Early Emergence of Hematopoietic Stem Cell Precursors With Adult Repopulating Potential and Fate

2021 ◽  
Vol 9 ◽  
Author(s):  
Wanbo Tang ◽  
Jian He ◽  
Tao Huang ◽  
Zhijie Bai ◽  
Chaojie Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mouse Model ◽  
Hematopoietic Stem Cells ◽  
Fetal Liver ◽  
Lineage Tracing ◽  
Genetic Lineage ◽  
Hematopoietic Stem ◽  
Genetic Lineage Tracing

In the aorta-gonad-mesonephros (AGM) region of mouse embryos, pre-hematopoietic stem cells (pre-HSCs) are generated from rare and specialized hemogenic endothelial cells (HECs) via endothelial-to-hematopoietic transition, followed by maturation into bona fide hematopoietic stem cells (HSCs). As HECs also generate a lot of hematopoietic progenitors not fated to HSCs, powerful tools that are pre-HSC/HSC-specific become urgently critical. Here, using the gene knockin strategy, we firstly developed an Hlf-tdTomato reporter mouse model and detected Hlf-tdTomato expression exclusively in the hematopoietic cells including part of the immunophenotypic CD45– and CD45+ pre-HSCs in the embryonic day (E) 10.5 AGM region. By in vitro co-culture together with long-term transplantation assay stringent for HSC precursor identification, we further revealed that unlike the CD45– counterpart in which both Hlf-tdTomato-positive and negative sub-populations harbored HSC competence, the CD45+ E10.5 pre-HSCs existed exclusively in Hlf-tdTomato-positive cells. The result indicates that the cells should gain the expression of Hlf prior to or together with CD45 to give rise to functional HSCs. Furthermore, we constructed a novel Hlf-CreER mouse model and performed time-restricted genetic lineage tracing by a single dose induction at E9.5. We observed the labeling in E11.5 AGM precursors and their contribution to the immunophenotypic HSCs in fetal liver (FL). Importantly, these Hlf-labeled early cells contributed to and retained the size of the HSC pool in the bone marrow (BM), which continuously differentiated to maintain a balanced and long-term multi-lineage hematopoiesis in the adult. Therefore, we provided another valuable mouse model to specifically trace the fate of emerging HSCs during development.

scholarly journals Definitive Hematopoietic Stem Cells Minimally Contribute to Embryonic Hematopoiesis

2021 ◽  
Author(s):  
Bianca A Ulloa ◽  
Samima S Habbsa ◽  
Kathryn S Potts ◽  
Alana Lewis ◽  
Mia McKinstry ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
De Novo ◽  
Marker Gene ◽  
Lineage Tracing ◽  
Hematopoietic Stem ◽  
Functional Potential ◽  
Injury Model ◽  
Rare Cells

Hematopoietic stem cells (HSCs) are rare cells that arise in the embryo and sustain adult hematopoiesis. Although the functional potential of nascent HSCs is detectable by transplantation, their native contribution during development is unknown, in part due to the overlapping genesis and marker gene expression with other embryonic blood progenitors. Using single cell transcriptomics, we defined gene signatures that distinguish nascent HSCs from embryonic blood progenitors. Applying a new lineage tracing approach, we selectively tracked HSC output in situ and discovered significantly delayed lymphomyeloid contribution. Using a novel inducible HSC injury model, we demonstrated a negligible impact on larval lymphomyelopoiesis following HSC depletion. HSCs are not merely dormant at this developmental stage as they showed robust regeneration after injury. Combined, our findings illuminate that nascent HSCs self-renew but display differentiation latency, while HSC-independent embryonic progenitors sustain developmental hematopoiesis. Understanding the differences among embryonic HSC and progenitor populations will guide improved de novo generation and expansion of functional HSCs.

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