Understanding hematopoiesis from a single-cell standpoint.

The cellular diversity of the hematopoietic system has been extensively studied, and a plethora of cell surface markers have been used to discriminate and prospectively purify different blood cell types. However, even within phenotypically identical fractions of hematopoietic stem and progenitor cells or lineage-restricted progenitors, significant functional heterogeneity is observed when single cells are analyzed. To address these challenges, researchers are now using techniques to follow single cells and their progeny to improve our understanding of the underlying functional heterogeneity. On November 19, 2015, Dr. David Kent and Dr. Leïla Perié, two emerging young group leaders, presented their recent efforts to dissect the functional properties of individual cells with a webinar series organized by the International Society for Experimental Hematology. Here, we provide a summary of the presented methods for cell labeling and clonal tracking and discuss how these different techniques have been employed to study hematopoiesis.MRC, Wellcome-Trust, BloodwiseThis is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.exphem.2016.03.00

A track of the clones: new developments in cellular barcoding.

International experts from multiple disciplines gathered at Homerton College in Cambridge, UK from September 12-14, 2018 to consider recent advances and emerging opportunities in the clonal tracking of hematopoiesis in one of a series of StemCellMathLab workshops. The group included 35 participants with experience in the fields of theoretical and experimental aspects of clonal tracking, and ranged from doctoral students to senior professors. Data from a variety of model systems and from clinical gene therapy trials were discussed, along with strategies for data analysis and sharing and challenges arising due to underlying assumptions in data interpretation and communication. Recognizing the power of this technology underpinned a group consensus of a need for improved mechanisms for sharing data and analytical protocols to maintain reproducibility and rigor in its application to complex tissues.We thank the BBSRC (BB/R021465/1), the German Stem Cell Network, the Wellcome-MRC Cambridge Stem Cell Institute and the Labex CelTisPhyBio (No. ANR-10-LBX-0038) for funds to support this workshop and the conference staff at Homerton Colleg

To portray clonal evolution in blood cancer, count your stem cells

International audienc

CellDestiny: A RShiny application for the visualization and analysis of single-cell lineage tracing data

International audienceSingle-cell lineage tracing permits the labeling of individual cells with a heritable marker to follow the fate of each cell's progeny. Over the last twenty years, several single-cell lineage tracing methods have emerged, enabling major discoveries in developmental biology, oncology and gene therapies. Analytical tools are needed to draw meaningful conclusions from lineage tracing measurements, which are characterized by high variability, sparsity and technical noise. However, the single cell lineage tracing field lacks versatile and easy-to-use tools for standardized and reproducible analyses, in particular tools accessible to biologists. Here we present CellDestiny, a RShiny app and associated web application developed for experimentalists without coding skills to perform visualization and analysis of single cell lineage-tracing datasets through a graphical user interface. We demonstrate the functionality of CellDestiny through the analysis of (i) lentiviral barcoding datasets of murine hematopoietic progenitors; (ii) published integration site data from Wiskott-Aldrich Symdrome patients undergoing gene-therapy treatment; and (iii) simultaneous barcoding and transcriptomic analysis of murine hematopoietic progenitor differentiation in vitro. In summary, CellDestiny is an easy-to-use and versatile toolkit that enables biologists to visualize and analyze single-cell lineage tracing data

Hematopoiesis in numbers

Hematopoiesis is a dynamic process in which stem and progenitor cells give rise to the ~10 13 blood and immune cells distributed throughout the human body. We argue that a quantitative description of hematopoiesis can help consolidate existing data, identify knowledge gaps, and generate new hypotheses. Here, we review known numbers in murine and, where possible, human hematopoiesis, and consolidate murine numbers into a set of reference values. We present estimates of cell numbers, division and differentiation rates, cell size, and macromolecular composition for each hematopoietic cell type. We also propose guidelines to improve the reporting of measurements and highlight areas in which quantitative data are lacking. Overall, we show how quantitative approaches can be used to understand key properties of hematopoiesis

The Branching Point in Erythro-Myeloid Differentiation

Development of mature blood cell progenies from hematopoietic stem cells involves the transition through lineage-restricted progenitors. The first branching point along this developmental process is thought to separate the erythro-myeloid and lymphoid lineage fate by yielding two intermediate progenitors, the common myeloid and the common lymphoid progenitors (CMPs and CLPs). Here, we use single-cell lineage tracing to demonstrate that so-called CMPs are highly heterogeneous with respect to cellular output, with most individual CMPs yielding either only erythrocytes or only myeloid cells after transplantation. Furthermore, based on the labeling of earlier progenitors, we show that the divergence between the myeloid and erythroid lineage develops within multipotent progenitors (MPP). These data provide evidence for a model of hematopoietic branching in which multiple distinct lineage commitments occur in parallel within the MPP pool

Citizen science. Toward transformative learning

Citizen science can raise people's understanding of science while helping scientists conduct their research. Yet its potential for driving transformative learning is empirically underexplored. We present the results of a preliminary study with secondary school students engaged in a long-term citizen science project, from the formulation of the research questions to data analysis and discussion. Students learnt about and increased their interest in neuroscience. They were also able to reflect on the role of science for society and valued their involvement as active participants in the research. We discuss the opportunities and challenges of approaching citizen science for transformative learning

Citizen science. Toward transformative learning

Citizen science can raise people's understanding of science while helping scientists conduct their research. Yet its potential for driving transformative learning is empirically underexplored. We present the results of a preliminary study with secondary school students engaged in a long-term citizen science project, from the formulation of the research questions to data analysis and discussion. Students learnt about and increased their interest in neuroscience. They were also able to reflect on the role of science for society and valued their involvement as active participants in the research. We discuss the opportunities and challenges of approaching citizen science for transformative learning