Hematology 101

What is Hematology 101?

It’s pretty much what it says on the tin. World-leading experts have been recruited from within the ISEH membership to help articulate the major themes in hematology and to review the most important tools used to define stem cells and their progeny. The goal is to provide a permanent and dynamic resource – providing a foundation on which future researchers can build. All slides and videos are available by clicking on the "select" button at the bottom of this page and I have summarized the first set of course modules below. We hope to expand this course over the coming years, and will draw on the support and enthusiasm of ISEH members to make it happen.

All modules are free and open to view, please get in touch if you have any questions.

David Kent, University of Cambridge (Course Director, Hematology 101)

(Hint: Some viewers have found it helpful/efficient to watch videos at 1.5X speed - just change your youtube settings!)

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Introduction

David Scadden, MD

http://hsci.harvard.edu/people/david-scadden-md

Introduction

The series starts with a lovely tale from Dr. David Scadden reaching back to the time of the ancients through to the present day. Dr. Scadden charts the story of blood from when it was to be “spilled for the gods” with a mystical and magical quality that drove life and weaves important discoveries throughout the journey, showing us how long these major concepts have really been arousing curiosity.

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Module 1 - What is Blood Stem Cell and How Do We Measure It?

Connie Eaves, PhD, FRS(C)

http://www.terryfoxlab.ca/people-detail/connie-j-eaves/

Mouse Stem and Progenitor Cells

Dr. Connie Eaves is long known for her passionate support of robust stem cell assays. In this video, Dr. Eaves charts the history of assay development in mouse HSC biology, gives a wonderful description of major analytical tools such as limiting dilution assays, and ends with her lab’s efforts to disentangle the functional and molecular heterogeneity of mouse blood stem cells.

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Elisa Laurenti, PhD

http://www.stemcells.cam.ac.uk/researchers/principal-investigators/elisa-laurenti

Human Stem and Progenitor Cells

In this presentation, Dr. Elisa Laurenti emphasizes the importance of studying human stem cells directly. Dr. Laurenti reminds us that humans and mice are quite different - different sizes, lifespans, and habits. In this presentation, she gives a broad overview of assays to detect human stem cell function and charts critical developments in the xenograft assay and its improved HSC detection.

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Module 2 - The Lifelong Journey of HSCs

Katrin Ottersbach, PhD

http://www.crm.ed.ac.uk/people/katrin-ottersbach

How Are the First HSCs Generated during Development?

Dr. Katrin Otterbach delivers an impressively concise yet broad description of the field of HSC emergence. Starting with a crash course in developmental biology, Dr. Ottersbach highlights the key differences between neonatal and adult stem cells – their different niches, their different functional capacities. One of the best aspects of this presentation is Dr. Ottersbach’s running dialogue about where strong evidence exists for a claim and where many things still need to be worked out before concepts enter the textbooks.

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Gerald de Haan, MSc, PhD

http://eriba.umcg.nl/people/gerald-de-haan/

How Do HSCs Age?

Dr. Gerald de Haan begins with a paradox - if HSCs have self-renewal, then how and why does our blood system age? If blood cell production ultimately derives from old HSCs, then understanding how HSCs age is of critical importance. Dr. De Haan catalogues the studies that have launched the field of HSC aging, sprinkles in some cutting edge technology in the form of DNA barcoding, and ends with a nice summary of the different ways that HSCs can age both genetically and epigenetically.

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Module 3 - HSCs and Disease

Timothy J. Ley, MD

http://oncology.wustl.edu/people/faculty/Ley/Ley_Bio.html

Acute Myeloid Leukemia

Dr. Timothy Ley presents gives an inspirational and impressively concise overview of AML biology and genomics. He begins with an overview of how AML presents in clinic and, in sharing current therapies, highlights the fact that mainstream therapy for de novo AML has not advanced much in the past 30 years. Dr. Ley goes on to frame everything with a nice model of how the sequence of mutations in AML drive the clone through pre-leukemic and outgrowth phases in a stepwise manner. However, he also offers fair warning about the combinatorial complexity of AML and a panoply of reasons why genetic profiling alone will not be sufficient to make major breakthroughs in clinical treatment of these patients. An absolutely fantastic learning tool for newcomers to AML biology.

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Dita Gratzinger, MD, PhD

https://profiles.stanford.edu/dita-gratzinger

The Human Bone Marrow in Health and Disease

Dr. Dita Gratzinger presents a compelling case for why cellular context matters in hematological malignancies - her overview of the bone marrow microenvironment and its dysregulation is tailored perfectly for a non-clinical scientific audience. Dr. Gratzinger goes through the maturation phases of blood cell types, the different types and areas of bone and highlights the fact that the bone marrow is a dynamic system that has major impacts on the cell types it houses. This is a must see for all of those new to thinking about stem cells and other blood cell lineages - location matters!

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Luigi Naldini, MD, PhD

http://www.hsr.it/research/organization/institutes/sr-tiget/luigi-naldini/details/2/

Hematopoietic Stem Cell Gene Therapy

In this comprehensive overview of gene therapy using blood cells, Dr. Luigi Naldini takes listeners through the basics, the clinical history, and the future potential of gene therapy using blood stem cells as the backbone. Dr. Naldini does not shy away from previous difficulties with early clinical trials and identifies key areas where improvements have been made already and where the future needs to focus its attention. Overall, this is an excellent base for newcomers to build from from one of the true pioneers of gene therapy in Europe.

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Andrew Elefanty, MD, PhD

https://www.mcri.edu.au/users/professor-andrew-elefanty

Hematopoietic Differentiation of Human Pluripotent Stem Cells

In this video, Dr. Andrew Elefanty delivers a fantastic overview of how scientists are making blood cells from pluripotent cells (both embryonic and induced pluripotent stem cell sources). Rather than giving a massive catalogue of different techniques from different groups, Dr. Elefanty strips down the process to the key components of all protocols and then focuses on the most recent advance that have been made in recent years. Overall, this video is a great balance of essential basic information for newcomers on differentiating pluripotent stem cells into blood but also includes some of the most exciting new techniques being tried today.

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Publications

Hematology 101

What is Hematology 101?

David Scadden, MD

Connie Eaves, PhD, FRS(C)

Elisa Laurenti, PhD

Katrin Ottersbach, PhD

Gerald de Haan, MSc, PhD

Timothy J. Ley, MD

Dita Gratzinger, MD, PhD

Luigi Naldini, MD, PhD

Andrew Elefanty, MD, PhD