Oxygen, hypoxia and the stem cell niche

Oxygen in Stem Cell Biology: A Critical Component of the Stem Cell Niche by Ahmed Mohyeldin, Tomás Garzón-Muvdi and Alfredo Quiñones-Hinojosa, Cell Stem Cell 2010(Aug 6); 7(2): 150-61. Review. [PubMed citation][FriendFeed entry]. Via Twitter @CellStemCell: Access [to the full text] is free in August worldwide so readers can try out new enhanced online format.

Abstract:

The defining hallmark of stem cells is their ability to self-renew and maintain multipotency. This capacity depends on the balance of complex signals in their microenvironment. Low oxygen tensions (hypoxia) maintain undifferentiated states of embryonic, hematopoietic, mesenchymal, and neural stem cell phenotypes and also influence proliferation and cell-fate commitment. Recent evidence has identified a broader spectrum of stem cells influenced by hypoxia that includes cancer stem cells and induced pluripotent stem cells. These findings have important implications on our understanding of development, disease, and tissue-engineering practices and furthermore elucidate an added dimension of stem cell control within the niche.

CIRM and Wisconsin sign a Declaration of Cooperation

Wisconsin Governor Jim Doyle and California’s State Stem Cell Agency Sign Declaration Of Cooperation to Advance Stem Cell Research toward Cures, News release, California Institute For Regenerative Medicine (CIRM), June 17, 2010. Excerpts:

The California Institute for Regenerative Medicine (CIRM) and the state of Wisconsin, coordinated through and led by the University of Wisconsin-Madison, expect to identify opportunities to further the advancement, promotion and funding of stem cell research and the development of stem cell therapies.

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CIRM currently has similar agreements with the Cancer Stem Cell Consortium of Canada, the State of Victoria in Australia, the JST in Japan, the MICINN in Spain, the MRC in the United Kingdom, the BMBF in Germany, MOST in China and the state of Maryland, and the New York Stem Cell Foundation.

Differences that separate normal vs cancer SC molecular circuitry

Pluripotent Transcription Factors Possess Distinct Roles in Normal versus Transformed Human Stem Cells by Junfeng Ji, Tamra E Werbowetski-Ogilvie, Bonan Zhong, Seok-Ho Hong and Mickie Bhatia, PLoS ONE 2009(Nov 30); 4(11): e8065 [FriendFeed entry][Full text is publicly accessible (via Libre OA)]. PubMed Abstract:

BACKGROUND: Cancer and normal stem cells (SCs) share proliferative properties of self-renewal and expression of key transcription factors (TFs). Despite similar TF identities, the functional role of specific TFs responsible for retaining SC state has yet to be examined in cancer. METHODOLOGY/PRINCIPAL FINDINGS: Here, we compare the role of Oct4 and Nanog, two-core pluripotent TFs, in transformed (t-hPSCs), and normal human pluripotent stem cells (hPSCs). Unlike normal SCs, self-renewal and survival of t-hPSCs were found to be independent of Oct4. In contrast, t-hPSCs exhibit hypersensitivity to reduction in Nanog and demonstrate complete loss of self-renewal coupled with apoptosis. Dual and sequential knockdown of Oct4 and Nanog revealed that sensitivity of t-hPSCs to Nanog was Oct4 dependent. CONCLUSIONS/SIGNIFICANCE: Our study indicates a bifurcation for the role of two-core SC and cancer related TFs in self-renewal and survival processes. We suggest that the divergent roles of these TFs establish a paradigm to develop novel therapeutics towards selective destruction of aggressive tumors harboring cancer stem cells (CSCs) with similar molecular signatures.

A contrarian view of 'stemness'

The 'stem cell' concept: is it holding us back? by Arthur D Lander, J Biol 2009(Sep 21); 8(8):70 [Epub ahead of print][Related FriendFeed entry][PubMed Citation][Full text is publicly accessible (via Libre OA)]. Abstract:

Developmental biology, regenerative medicine and cancer biology are increasingly occupied with the molecular characterization of stem cells. Yet recent work adds to a growing body of literature suggesting that 'stemness' cannot be reduced to the molecular features of cell types, and is instead an emergent property of cell lineages under feedback control.

Brief excerpt from the full text: "Like gene or phlogiston, the term 'stem cell' is a scientific concept. Stem cells are very much in the news, thanks to a dramatic upsurge in interest in their therapeutic potential".

Another excerpt from the full text:

For example, in the case of cancers that are stem cell driven, it is not clear that we actually have grounds to assume that the specific chemotherapeutic targeting of cancer stem cells will necessarily stop tumors in their tracks. Indeed, if feedback and lineage progression continue to take place in cancerous tissues, we might observe that, under different conditions - different stages of tumorigensis, different parts of a tumor, different amounts of tumor cells - that different cell types will assume the role of 'cancer stem cell'. The therapeutic implications of this possibility are clearly substantial.

An interview with Arthur Lander is at: Q&A: Is stem cell research misguided? by Bob Grant,TheScientist.com, September 29, 2009 [FriendFeed entry].

Comment: The major contrarian perspective in this opinion piece is the comparison of the stem cell concept with the phlogiston concept. This comparison is discussed further in the Q & A interview. The Comments section of Dr. Lander's article includes an answer to a question that I asked: What about purified stem cells? As part of a discussion on FriendFeed, I also asked: Is the debate about 'stemness' becoming another version of the nature-nurture debate? So far, no response to this question.

Awards for Connie Eaves and John Dick

Canadian stem cell researchers Eaves and Dick to receive hematology awards, Michael Rudnicki, Stem Cell Network blog, July 31, 2009. Excerpts:

Connie Eaves, PhD, of the BC Cancer Agency, University of British Columbia in Vancouver, will be presented with the Henry M. Stratton Medal, which honors an individual whose well-recognized contributions to hematology have taken place over a period of several years. Dr. Eaves will receive this award for her remarkable achievements in the area of stem cell biology for more than two decades. Dr. Eaves has been on the cutting edge of adapting or introducing technologies related to stem cell biology, especially her ground-breaking techniques of using the long-term culture system as means of understanding the proliferative and renewal properties of normal and malignant primitive human hematopoietic stem cells.

John E. Dick, PhD, of the University Health Network in Toronto, will be recognized with the E. Donnall Thomas Lecture and Prize for his pioneering research into the development of human leukemia, which has transformed the view of how leukemia progresses. This prize, named after a Nobel Prize laureate and past Society president, recognizes pioneering research achievements in hematology.

These summaries were obtained from: Six Researchers to Receive Prestigious Awards From the American Society of Hematology, Press Release, American Society of Hematology, July 13, 2009.

Comment: Very appropriate recognition of accomplishments in hematological research that have included important contributions to cancer research.

Ontario Research Fund competition includes support for SC research

From the Programs & Funding page of the Ontario Ministry of Research and Innovation: Global Leadership Round in Genomics & Life Sciences (GL2) Competition Overview. Excerpts:

The Ontario Research Fund - Global Leadership Round in Genomics & Life Sciences (GL2) promotes research excellence in Ontario by supporting transformative, internationally significant research in genomics and gene-related areas of research. International collaboration is strongly encouraged for projects submitted to this competition.

The competition provides an opportunity for the province to fund truly transformative research and build on an area where Ontario researchers have demonstrated world-leading strength.

The Ontario Research Fund - Global Leadership Round in Genomics & Life Sciences competition focuses on scientific excellence and strategic value to Ontario, and targets leading-edge, large-scale research initiatives.

The minimum support provided by the GL2 to a project is $3.5 million.

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What’s eligible for funding?

The Ministry encourages collaborative, transformational projects across institutions from the following areas:

* Genomics and Genomics-related research (human health, plants and animals)
* Stem cell research
* Proteomics research

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When is the deadline for proposals?

The deadline for Notices of Intent is June 15, 2009.
The deadline for proposals is August 31, 2009.