Stem Cell Workshop Covered Field’s Progress, Challenges and Opportunities

In the decade since NIGMS began supporting human embryonic stem cell (hESC) research, the field has made substantial strides, including the development of methods to generate induced pluripotent stem cells (iPSC). As part of our ongoing commitment to basic research into the fundamental properties of pluripotent cells, we recently hosted our fourth biennial workshop for NIGMS grantees working in this research area. The 63 participants presented their latest research findings, exchanged ideas and discussed possibilities for collaboration.

The talks and posters focused on state-of-the-art hESC and iPSC research in four broad areas: pluripotency and self-renewal, technological approaches, differentiation mechanisms, and epigenetics and reprogramming. Several presentations highlighted significant advances in our understanding of the molecular complexes and signaling networks that control pluripotency and the transition to the differentiated state. As in previous workshops, it was exciting to see all the progress that has been made in the past two years.

The final session was on future directions and challenges. It included a discussion of the current state of the field and raised the important question of the nature, extent and significance of differences between hESC and iPSC. Jamie Thomson of the University of Wisconsin-Madison reminded everyone that these two types of pluripotent cells are remarkably similar and that differences may reflect genetic differences in the original cells and/or differences arising during growth in tissue culture.

The meeting concluded with a lively discussion that highlighted the participants’ opinions on the technical challenges, resource needs and key biological questions that will drive the field in the coming years. For more on this, read the workshop summary.

NIGMS Cell Repository Now Includes iPS Cell Lines

The HGCR iPS cell lines undergo extensive characterization, including assessment of their capacity to differentiate into specialized cell types. The cell shown here was directed to differentiate into a nerve cell.As we anticipated last year, the NIGMS Human Genetic Cell Repository Exit icon (HGCR) now offers human induced pluripotent stem cell lines that carry disease gene mutations. The first five lines to be made available were derived from individuals with Huntington’s disease, juvenile onset diabetes, severe combined immunodeficiency disease, muscular dystrophy and spinal muscular atrophy. The repository is developing more cell lines representing other diseases.

The iPS cell lines Exit icon, along with more than 10,000 others in the repository, are comprehensively characterized to ensure their identity, stability and purity. This quality control makes the repository an excellent resource for researchers who need well-characterized, disease-specific cells.

You can order any of the repository’s cell lines via the HGCR catalog Exit icon.

New Funding Opportunity for Stem Cell Researchers

NIGMS has just issued a call for Program Projects for Collaborative Research on the Basic Biology of Pluripotency and Reprogramming (P01), with an emphasis on human induced pluripotent stem (iPS) cells. We are particularly interested in studies that propose comprehensive analyses of the basic biology of pluripotency, the molecular events and mechanisms of reprogramming, and the epigenetics and epigenomics of the pluripotent and reprogrammed states.

These applications have special requirements, so please read the announcement carefully. Letters of intent are due on November 1, and applications are due on December 1.

If your research involves stem cells but isn’t appropriate for this announcement, you may submit an investigator-initiated R01 application that addresses the basic biology of stem cells and/or uses these cells as model systems to study fundamental life processes.

You may contact me at hayness@nigms.nih.gov or Marion Zatz at zatzm@nigms.nih.gov with questions about this new opportunity or about NIGMS support for stem cell research.

Update: Status of hESC Applications and Grants

NIH has rescinded the earlier notice regarding the status of applications and grants involving human embryonic stem cells. The new notice states that the receipt, processing, review and awarding of NIH applications and proposals involving human embryonic stem cells will continue. It goes on to list the following actions:

  • The suspension of further NIH activity to implement, apply or act pursuant to the NIH Guidelines is hereby lifted.
  • The suspension of the issuance of all pending competing, and noncompeting continuation hESC awards and contracts approved for funding is hereby lifted.
  • The suspension of the peer review of all pending competing hESC applications and proposals is hereby lifted.
  • The NIH Human Embryonic Stem Cell Registry will resume accepting submissions of information about hESC lines for the purpose of establishing eligibility for funding under the NIH Guidelines. The NIH review of hESC lines for inclusion on the Registry under the NIH Guidelines will also resume.

Status of hESC Applications and Grants

NIH has issued a notice describing the status of applications and grants that propose research using human embryonic stem cells (hESC). Among its points are:

  • Any further NIH activity to implement, apply or act pursuant to the NIH Guidelines is hereby suspended until further notice.
  • Issuance of all pending competing, and noncompeting continuation hESC awards and contracts is suspended until further notice.
  • The peer review of all pending competing hESC applications and proposals is suspended until further notice.

Grants affected include all types of research and training. We expect more guidance soon and will let you know when it’s posted.

Early Notice: Program Projects for Collaborative Research on the Basic Biology of Pluripotency and Reprogramming

It’s safe to say that the discovery that human non-embryonic cells can be reprogrammed to an embryonic stem cell-like state has created a lot of excitement in the scientific community. These cells provide a wonderful opportunity to investigate the fundamental molecular and genetic properties of pluripotent cells.

Last month, the NIGMS Council approved a new grant program that will focus on studying the basic biology of pluripotency and reprogramming, with an emphasis on human induced pluripotent stem (iPS) cells. This initiative will use the program project (P01) mechanism to support collaborative research that advances a comprehensive understanding of the basic biology of pluripotency, the molecular events and mechanisms of reprogramming, and the epigenetics and epigenomics of the pluripotent and reprogrammed states.

Once the funding opportunity announcement has been published in the NIH Guide later this summer, we will post it on the Feedback Loop site. In the meantime, I encourage you to start talking with potential collaborators and thinking about applying.

NIGMS Cell Repository Will Expand Collection, Services

Coriell’s cryogenic tanks filled with liquid nitrogen and millions of vials of frozen cells. Credit: Coriell Institute for Medical Research

Good news—we just awarded a five-year contract to the Coriell Institute for Medical Research to continue and expand operation of the NIGMS Human Genetic Cell Repository (HGCR) Exit icon.

A lot of NIGMS grantees who do basic research may not be familiar with the HGCR. It currently has more than 10,000 cell lines from individuals who have genetic disorders and those who do not. The cell lines, each of which has been comprehensively characterized and is contaminant-free, represent nearly 1,000 disorders. An equally important element of the HGCR is the human variation collection, which includes samples from populations around the world.

Under the new contract, the repository will continue to acquire, characterize and distribute cell cultures and DNA samples. In the coming months, it will add induced pluripotent stem cell lines that researchers can use to study inherited diseases and the regulation of normal cell differentiation. To respond to the changing needs within the genetics community, the repository will also start accepting custom orders.

One of the real advantages of ordering materials from the repository has been and certainly will continue to be the high level of characterization and quality control.

You can read more about the repository in the NIGMS news release. You can also go to the HGCR online catalog Exit icon to see what cell lines are available.

If you’ve used the repository, let me know what you think. If you haven’t, keep it in mind for future studies—it’s a great resource for getting good quality human cell lines, especially ones that may otherwise be difficult to obtain.

First Human Embryonic Stem Cell Lines Approved Under New Guidelines Now Available

NIH Director Francis Collins announced today that the first 13 human embryonic stem cell (hESC) lines to be approved under the new NIH Guidelines for Human Stem Cell Research have been placed on the NIH Human Embryonic Stem Cell Registry, and NIH grantees may now use them. These lines were not previously eligible for NIH funding under the 2001 guidelines.

Investigators whose grants were awarded with restrictions on using the funds for hESC research should check the registry to determine if any of the lines are suitable for their projects. Please see today’s NIH Guide notice for more details, including procedures on how to request that the award restrictions be lifted.

An additional 96 lines have been submitted for inclusion in the registry. We expect that more will become eligible for use in the coming months.

NIGMS Grantees Gather to Report on Stem Cell Research—Progress and Challenges

Image of poster for the 3rd NIGMS Workshop on Human Embryonic Stem Cell Research: Recent Progress and Future Directions of NIGMS GranteesHuman embryonic stem cell research is an area of special interest to NIGMS. It represents a unique opportunity to explore the most fundamental mechanisms of biology and development while providing a foundation for future clinical applications. NIGMS’s support of basic research in embryonic stem cell biology is actually greater than that of any other component of NIH.

As part of our continuing commitment to this research area, we hosted our third workshop that brought together 54 NIGMS grantees working on human embryonic stem cells. Each workshop helps them exchange ideas and pursue collaborations while informing us about their progress and challenges.

The research presented during the talks and poster session at this year’s meeting covered a broad array of topics, reflecting the most up-to-date (and unpublished) work from labs across the country. It was wonderful to see how much progress has been made since the previous workshop two years ago! Sessions focused specifically on advances that help us understand how cells self-renew, how and when differentiation occurs and what directs cell fates. Another session discussed technological developments, such as large-scale culture techniques and the application of cutting-edge approaches in proteomics, glycoproteomics and global mapping of chromosomal interactions. Grantees also shared their latest progress on induced pluripotent stem cells and genetic reprogramming.

After listening to the presentations, it became clear to me that one of the pivotal directions for future stem cell research is going to be epigenetics, especially as it relates to regulating pluripotency, directing cell fate and inducing genetic reprogramming. Several talks, for instance, showed how two different but genetically similar human embryonic stem cell lines give rise to distinct cell types under the same conditions, presumably due to pre-existing epigenetic marks.

Since the last meeting in 2007, we’ve seen the remarkable development of human induced pluripotent stem cells. But as Jamie Thomson suggested in the closing session, we won’t be able to decipher critical differences between these cells and human embryonic stem cells until we really understand the range of variability in both types of cells. Given the accelerating pace of progress, I expect that future research will generate many new insights and perhaps some surprises that we’ll hear about in the next two years.

Moving Forward with Stem Cell Research

New NIH guidelines for human stem cell research became effective on July 7, 2009. We thank those of you who provided comments on the draft policy. The input NIH received was instrumental in developing the final guidelines, which will generate a new registry of human embryonic stem cells (hESC) eligible for use in NIH-funded projects. This registry will be posted at http://grants.nih.gov/stem_cells/registry/current.htm.

NIH has now issued guidance on the status of applications and awards under the new guidelines. I’ve summarized the main points below, but see the notice for other important details.

New and competing applications may be submitted and reviewed. Until eligible hESC lines are listed in the new NIH registry, applicants should not identify a specific line, but should state that they will use line(s) from the registry.

Ongoing awards that use previously approved NIH hESC lines may continue to use these lines for research for the duration of the currently approved award.

Administrative supplements (including Recovery Act ones) may be funded if the supplemental activities use the same hESC lines approved for the parent grant.

Previously reviewed pending applications may now be awarded. However, these awards will be restricted from using funds for hESC research until the hESC lines to be used have been posted on the new registry.

The NIH guidelines and notice represent important steps forward in removing previous barriers to hESC research and advancing this very exciting and significant area of science.