Crimson News > David Baltimore


David Baltimore will visit Argentina during 01-02 November 2012 to give a number of presentations open to the entire Argentine academic community.



Induced Pluripotent Stem Cells Generated Without Viral Integration

Pluripotent stem cells have been generated from mouse and human somatic cells by viral expression of the transcription factors Oct4, Sox2, Klf4, and c-Myc. A major limitation of this technology is the use of potentially harmful genome-integrating viruses. Here, we generate mouse induced pluripotent stem cells (iPS) from fibroblasts and liver cells by using nonintegrating adenoviruses transiently expressing Oct4, Sox2, Klf4, and c-Myc. These adenoviral iPS (adeno-iPS) cells show DNA demethylation characteristic of reprogrammed cells, express endogenous pluripotency genes, form teratomas, and contribute to multiple tissues, including the germ line, in chimeric mice. Our results provide strong evidence that insertional mutagenesis is not required for in vitro reprogramming. Adenoviral reprogramming may provide an improved method for generating and studying patient-specific stem cells and for comparing embryonic stem cells and iPS cells.

Read more about Dr. Weir´s paper in Science

Go to Supplemental Data



Induced Pluripotent Stem Cells Generated from Patients with ALS Can Be Differentiated into Motor Neurons

The generation of pluripotent stem cells from an individual patient would enable the large-scale production of the cell-types affected by that patient’s disease. These cells could in turn be used for disease modeling, drug discovery, and eventually autologous cell-replacement therapies. Although recent studies have demonstrated the reprogramming of human fibroblasts to a pluripotent state, it remains unclear whether these induced pluripotent stem (iPS) cells can be produced directly from elderly patients with chronic disease. We have generated iPS cells from an 82-year-old woman diagnosed with a familial form of amyotrophic lateral sclerosis (ALS). These patient-specific iPS cells possess properties of embryonic stem cells and were successfully directed to differentiate into motor neurons, the cell type destroyed in ALS.

Read more about Dr. Eggan's paper in Science

Read comment by Constance Holden 



Satellite cells reside beneath the basal lamina of skeletal muscle fibers and include cells that act as precursors for muscle growth and repair. Although they share a common anatomical localization and typically are considered a homogeneous population, satellite cells actually exhibit substantial heterogeneity. We used cell-surface marker expression to purify from the satellite cell pool a distinct population of skeletal muscle precursors (SMPs) that function as muscle stem cells. When engrafted into muscle of dystrophin-deficient mdx mice, purified SMPs contributed to up to 94% of myofibers, restoring dystrophin expression and significantly improving muscle histology and contractile function. Transplanted SMPs also entered the satellite cell compartment, renewing the endogenous stem cell pool and participating in subsequent rounds of injury repair. Together, these studies indicate the presence in adult skeletal muscle of prospectively isolatable muscle-forming stem cells and directly demonstrate the efficacy of myogenic stem cell transplant for treating muscle degenerative disease.

Read more about Dr. Wagers' article in Cell

Go to Supplemental Data 



The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a poorly understood key event in breast tumor progression. Here, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a model of human DCIS and primary breast tumors. Progression to invasion was promoted by fibroblasts and inhibited by normal myoepithelial cells. Molecular profiles of isolated luminal epithelial and myoepithelial cells identified an intricate interaction network involving TGFb, Hedgehog, cell adhesion, and p63 required for myoepithelial cell differentiation, the elimination of which resulted in loss of myoepithelial cells and progression to invasion.

Read Poliak's article in Cancer Cell 



EGR1 is a member of the immediate early response transcription factor family and functions in cell growth, development, and stress responses in many tissues. Here we report an additional role for EGR1 in regulating homeostasis of hematopoietic stem cells (HSCs). HSCs normally express Egr1 at high levels, but dramatically downregulate its expression when induced to divide and migrate. Consistent with this finding, mice lacking Egr1 exhibit significant increases in steady-state levels of dividing HSCs in the bone marrow (BM), and a striking spontaneous mobilization of HSCs into the peripheral blood. These data identify EGR1 as a transcriptional regulator of stem cell migration that normally functions to promote HSC quiescence and retention in the niche. The ability of this single factor to regulate both proliferation and mobilization of HSCs suggests that EGR1 commands a genetic program that coordinates stem cell division and migration to maintain appropriate HSC number and function.

Read more about Dr. Wagers' article in Cell Stem Cell

Go to Supplemental Data 



There is increasing evidence showing that the stromal cells surrounding cancer epithelial cells, rather than being passive bystanders, might have a role in modifying tumor outgrowth. The molecular basis of this aspect of carcinoma etiology is controversial. Some studies have reported a high frequency of genetic aberrations in carcinoma-associated fibroblasts (CAFs), whereas other studies have reported very low or zero mutation rates. Resolution of this contentious area is of critical importance in terms of understanding both the basic biology of cancer as well as the potential clinical implications of CAF somatic alterations. We undertook genome-wide copy number and loss of heterozygosity (LOH) analysis of CAFs derived from breast and ovarian carcinomas using a 500K SNP array platform. Our data show conclusively that LOH and copy number alterations are extremely rare in CAFs and cannot be the basis of the carcinoma-promoting phenotypes of breast and ovarian CAFs.

Read more about Polyak's article 

Go to Supplemental data



Multipotent cardiac progenitor cells are found in the fetal and adult heart of many mammalian species including humans and form as intermediates during the differentiation of embryonic stem cells. Despite similar biological properties, the molecular identities of these different cardiac progenitor cell populations appear to be distinct. Elucidating the origins and lineage relationships of these cell populations will accelerate clinical applications such as drug screening and cell therapy as well as shedding light on the pathogenic mechanisms underlying cardiac diseases.

Read Wu's article in Cell 



Public engagement in scientific research has gone viral. Today, public consultation is invoked for subjects as diverse as war veterans' responses to genomic research, responsible nanotechnology and the use of animal transplants in humans. It has also gone global, as demonstrated by the just-completed consultation on research using animal–human hybrid embryos by Britain's Human Fertilisation and Embryology Authority (HFEA), and the Singapore government's plan to consult on hybrid research and oocyte donation later this year. As groups of citizens mobilize and blog on science issues — from patenting to public health and drug development — it is time to reconsider the ground rules for public debates on science.

Read Taylor's article in Nature


Despite debates over technologies and statistics, a new catalog of genes associated with colon and breast cancer is close at hand.

Read comment by Jeffrey M. Trent and Jeffrey W. Touchman

Read Polyak's article in Science 



Using human eggs in the quest to make donor-specific embryonic stem
cells is controversial. A method developed in mice, if applicable to humans,
could eliminate the need to obtain eggs for this purpose.

Read comment by Alan Colman and Justine Burley 

Read Eggan's article in Nature