The National Institute of Diabetes & Digestive & Kidney Diseases

Trans-NIDDK Strategic Planning: Stem Cells and Developmental Biology Planning Group Meeting Summary

September 19, 2000

Overview

The purpose of this working group, and its counterparts on Genetics, Genomics & Bioinformatics and on Clinical Trials and Epidemiology, is to help the NIDDK set priorities for research support in critical scientific and biomedical areas. The intent is to obtain the best possible advice from leading investigators in these areas. The current working groups may be followed by additional groups in other areas.

Stem cell and developmental biology is in a time of interesting opportunities and flux, particularly with the release of NIH guidelines for human embryonic stem cell research. The NIDDK wishes to identify the critical questions in this area, and, in collaboration with other NIH Institutes, determine the most opportune directions for research. Of critical importance is ensuring that appropriate resources are available, including bioinformatics, searchable databases, cDNA libraries, purified growth factors, and reproducible assays. The existence of animal models and training mechanisms also are essential.

Opportunities for Research

1. Understanding the process of how pluripotent stem cells become multipotent progenitor cells
2. Understanding plasticity of adult stem cells
   1. Transdifferentiation: Reports of homing of hematopoietic stem cells to other organs and expression of different fates. e.g., nervous system
   2. Role of stem cells in replacement therapy
3. Defining characteristics of adult vs. embryonic stem cells
4. Understanding the role of stem cells in the formation of tissues and organs
5. Understanding the process of regeneration vs. normal development
6. Exploring the therapeutic potential of manipulating stem cells prior to therapeutic use

Infrastructure Needs

1. Ihor Lemischka's report in Science on gene profiling in hematopoietic stem cells shows the kind of information base that is needed.
2. Searchable, annotated databases of expressed genes in stem cells
3. Searchable databases of reagents expressed in stem cells, such as cDNAs, growth factors and their receptors, identifiable intrinsic properties of "stem-ness"
4. Reagent distribution network
5. Monoclonal antibodies directed at cell surface markers
6. Small business community should be enlisted to make cDNAs, antibodies, etc.
7. Develop clonogenic assays, in vivo and ex vivo, including animal models
8. Training and community building, to take advantage of regulatory paradigms developed in diverse systems, including both vertebrate and invertebrate models.
9. Informatics training
10. Supply of tools allowing visualization of data
11. New software development
12. Application of tools to large datasets, to identify cluster patterns of expression, prediction of protein expression

Committee Process

1. Description of research needs in areas of interest to the NIDDK
   1. Bone marrow, stomach/intestine, pancreas, liver, prostate and bladder/kidney
   2. Bone also is of interest, particularly to investigators of fundamental stem cell biology
2. The working group will form subcommittees with added experts in the following areas:
   1. Early development, embryonic stem cells (Brigid Hogan, Kenneth Zaret, Doug Melton, Igor Dawid)
   2. Hematopoeisis (Len Zon, Irv Weissman, Ihor Lemishka, Peter Quesenberry)
   3. Gut (Jeff Gordon)
   4. Prostate, bladder, kidney (Anthony Atala, Mark Hammerman, Qais Alawqati, Barbara Ballermann)
   5. Liver (Rebecca Taub)
   6. Bone (Gerard Karsenty, Steve Teitelbaum, Henry Kronenberg)
3. Subcommittees are to be formed by mid-October, with a plan to transmit an interim report to Council in February.
4. Report to be placed on the NIDDK web site to gain comments from the research community
5. Advertisement to professional societies

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