WELLCOME IMAGES, PAUL APPLETON, UNIVERSITY OF DUNDEE
1. New method for generating iPSCs
There are several drawbacks to existing methods of reprogramming somatic cells into induced pluripotent stem (iPS) cells , such as the alteration of the cell’s genome through the use of retroviruses and other genetic elements for transfection of the reprogramming transcription factors. Now, by transfecting chemically modified mRNAs to encode five necessary transcription factors, researchers can turn four human cell types into genetically unmodified iPS cells with high efficiency and without activating an innate immune response—reducing cytotoxity and the risk of the cells becoming cancerous.
L. Warren, et al., “Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA,” Cell Stem Cell, 7:618-30, 2010. Free F1000 evaluation
2. Stem cells, now in 3-D
Through a three-step protocol that involves treatment with growth factors and signaling molecules, researchers differentiated...
J.R. Spence, et al., “Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro,” Nature, 470:105-9, 2011.
3. Giving rise to blood
For the first time, researchers convert human fibroblasts—collagen-secreting cells found in connective tissue—into myeloid progenitor cells, which give rise to blood cells such as granulocytes, monocytes, and erythrocytes. Surprisingly, they did this through the expression of a single transcription factor, OCT4, along with treatment of cytokines that promote the growth of hematopoietic cells.
E. Szabo, et al., “Direct conversion of human fibroblasts to multilineage blood progenitors,” Nature, 468:521-6, 2010.
The mechanosensitive sensory hair cells of the inner ear are some of the most complex, specialized cells in the body and are crucial for hearing and balance. Because the body is unable to regenerate them, they are a coveted target for the development of therapies for hearing loss. Researchers at Stanford University develop a stepwise procedure using mouse embryonic and induced pluripotent stem cells that mimics the early stages of ear development, generating hair cells that produce currents in response to mechanical stimulation.
K. Oshima, et al., “Mechanosensitive hair cell-like cells from embryonic and induced pluripotent stem cells,” Cell, 141:704-16, 2010. Free F1000 evaluation
5. The making of neurons
Researchers directly reprogram mouse fibroblasts into functional neurons for the first time, using just three transcription factors (Ascl1, Brn2 and Myt1l). After just one week, the neurons exhibited spontaneous and rhythmic network activity.
T. Vierbuchen, et al., “Direct conversion of fibroblasts to functional neurons by defined factors,” Nature, 463:1035-41, 2010.
6. Fixing telomeres
Dyskeratosis congenita (DC) is a rare disorder associated with mutations in telomerase and a protective complex called TERC, which result in shortened telomeres. Researchers find that when fibroblasts from DC patients are reprogrammed into iPS cells, there is an increase production of TERC and other telomerase components, leading to longer telomeres.
S. Agarwal, et al., “Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients,” Nature, 464:292-6, 2010.
7. MicroRNAs and pluripotency
Recently, microRNAs (miRNAs) have been found to be important players in regulating the pluripotency of cells. In this study, researchers identify and describe two miRNA families—the ESC cycle regulating (ESCC) and the let-7 miRNA family—which play opposite roles in blocking and promoting the self-renewal of mouse embryonic stem cells.
C. Melton, et al., “Opposing microRNA families regulate self-renewal in mouse embryonic stem cells,” Nature, 463:621-6, 2010.
The F1000 Top 7 is a snapshot of the highest ranked articles based on a custom search (using the terms "stem cells iPS") on Faculty of 1000, as calculated on July 15, 2011. Faculty Members evaluate and rate the most important papers in their field. To see the latest rankings, search the database, and read daily evaluations, visit http://f1000.com.