In the end, the team found that injecting a cocktail of five genes — the 3 - gene GMT mix plus the genes ESRRG and MESP1 — were sufficient to reprogram
the fibroblasts into heart - like cells.
W. Hu et al., «Direct conversion of normal and Alzheimer's disease human
fibroblasts into neuronal cells by small molecules,» Cell Stem Cell, doi: 10.1016 / j.stem.2015.07.006, 2015.
In a series of groundbreaking studies, Shinya Yamanaka, MD, PhD, a senior investigator at the Gladstone Institutes, identified the molecular factors that can convert
fibroblasts into stem cells (termed induced pluripotent stem cells).
The next step proved even more promising: when we introduced these three genes into the injured hearts of living mice, we were again able to convert
fibroblasts into new heart cells, and these cells helped improve heart function, integrating with the old ones and beating in synchrony with the rest of the heart.
Since murine NSCs have been «primed» with several of the factors originally discovered to reprogram
fibroblasts into iPS cells, they represent an attractive source of starting material for iPS cell induction studies.
Remarkably, a combination of just three of the factors (Gata4, Mef2c, and Tbx5) was enough to efficiently convert
fibroblasts into cells that could beat like cardiomyocytes and turned on most of the same genes expressed in cardiomyocytes.
Conversion of mouse
fibroblasts into cardiomyocytes using a direct reprogramming strategy.
Oct4, Sox2, c - Myc, and Klf4 were the four original factors that were capable of converting mouse and human
fibroblasts into iPs cells [1], [3], [5], [11], [12].
Yangqing et al recently had success in pursuing this pathway — turning chicken
fibroblasts into «germ - like» cells in the same way that induced pluripotent stem cells are made2.
In his laboratory mice, Dr. Ding has now used chemical reprogramming to turn
fibroblasts into neural «precursor» cells with the potential to become new oligodendrocytes.
Dr. Ding's work revolves around chemical reprogramming — the use of small molecule drug mixtures to coax
fibroblasts into becoming a variety of other cell types.
To convert
the fibroblasts into muscle cells, the researchers transfected the fibroblasts with the cDNA of MyoD, forcing the cells to express MyoD (Davis et al., 1987).
So the lab of Vania Broccoli, from the San Raffaele Institute in Milan, set out to reprogram
fibroblasts into dopaminergic neurons.
From all these studies, Ascl1 emerged as a key player of reprogramming
fibroblasts into induced neurons.
The Joslin researchers «reprogrammed»
the fibroblasts into iPSCs by using viral procedures that activated four genes that together maintain cells in the iPSC state.
They found that another triad of transcription factors succeeded in converting
fibroblasts into green fluorescent cells.
• In March, a University of Wisconsin team reprogrammed skin
fibroblasts into embryonic stem cells without incorporating the viral or other foreign DNA that can lead to complications like cancer.
Other co-authors of the study, «Selective conversion of
fibroblasts into peripheral sensory neurons,» were Valentina Lo Sardo, Rachel K. Tsunemoto, Daniel Williams, and Pietro Paolo Sanna, all of TSRI; and Attila Szűcs of the University of California San Diego, who performed many of the electrical tests on the induced neurons.
They found that the combination of the transcription factors Brn3a plus Ngn1, or Brn3a plus Ngn2, reprogrammed a significant percentage of the embryonic mouse
fibroblasts into what looked — and acted — like mature DRG - type sensory neurons.
In the online edition of Science, he and his colleagues report that Oct4 and Sox2 were capable of converting neonatal foreskin
fibroblasts into cells similar to Yamanaka's, whereas Nanog significantly boosted the frequency of reprogramming and Lin28 upped it by a moderate amount.
The team also transplanted treated
fibroblasts into the hearts of live mice, where they developed into cardiomyocytes (Cell, DOI: 10.1016 / j.cell.2010.07.002).
They turned
the fibroblasts into stem cells and noticed that in the process, some of the cells lost the extra sex chromosome.
The effects of therapeutic lasers in wound healing include vasodilation, angiogenesis, increased collagen synthesis by fibroblast, differentiation of
fibroblast into myofibroblasts, stimulation of leukocytes, and enhanced antioxidant activity.
Not exact matches
Repeated transfection of two expression plasmids, one containing the complementary DNAs (cDNAs) of Oct3 / 4, Sox2, and Klf4 and the other containing the c - Myc cDNA,
into mouse embryonic
fibroblasts resulted in iPS cells without evidence of plasmid integration, which produced teratomas when transplanted
into mice and contributed to adult chimeras.
Marius Wernig and colleagues at Stanford University in California discovered that inserting a cocktail of three genes
into fibroblasts turns them directly
into neurons in just days.
The researchers — James Robl, a developmental biologist and his colleagues at the University of Massachusetts at Amherst, and Steve Stice at Advanced Cell Technology in Worcester, Massachusetts — inserted a marker gene fused with a gene for resistance to the chemical neomycin
into a culture of connective tissue cells called
fibroblasts.
These cellular contractors tell
fibroblasts to move
into an injury to begin the healing process.
About twice as many
fibroblasts migrated
into the daytime wounds as nighttime ones.
The study team removed
fibroblasts (skin cells) from DBA patients, and in cell cultures, using proteins called transcription factors, reprogrammed the cells
into iPSCs.
Hayashi then drew on other research showing that one key regulatory molecule (activin A) and a growth factor (basic
fibroblast growth factor) could convert cultured early embryonic stem cells
into cells akin to epiblasts.
To find out, Deb and his co-authors genetically tagged cardiac
fibroblasts in mice and watched as they transitioned
into bone - forming, osteoblast - like cells after heart injury.
Homologous recombination was used to introduce a nominally transforming mutation
into an endogenous H - ras1 gene in Rat1
fibroblasts.
The orbital remodeling in TED is likely induced by infiltrating T lymphocytes and mast cells, which activate orbital
fibroblast effector cells to either proliferate and form scar - producing cells called myofibroblasts or turn
into pro-inflammatory fat cells.
Researchers from the UNC School of Medicine have discovered that cells called
fibroblasts, which normally give rise to scar tissue after a heart attack, can be turned
into endothelial cells, which generate blood vessels to supply oxygen and nutrients to the injured regions of the heart, thus greatly reducing the damage done following heart attack.
Cells called cancer - associated
fibroblasts arrange a normal meshwork of fibers
into straight tracks, cell biologist Begum Erdogan of Vanderbilt University in Nashville and colleagues reported December 13 at the annual meeting of the American Society for Cell Biology.
That is, instead of just 30 percent of
fibroblasts naturally switching
into endothelial cells, 60 percent made the switch.
«It appears that injury itself can induce
fibroblasts to change
into endothelial cells so the heart heals better.
But Erdogan and colleagues found that
fibroblasts associated with prostate cancer could either lay straight new fibronectin tracks or grab and pull snarled networks
into straightaways that cancer cells could then move along.
The green blood vessels running horizontally are partly composed of red / yellow cells, suggesting that
fibroblasts are incorporated
into blood vessels.
Researchers used the CRISPR / Cas9 gene editing technique to introduce a segment of a human gene causing Huntington's, with a very long glutamine repeat region,
into pig
fibroblast cells.
For the new study, the team used a cell - reprogramming technique (similar to those used to reprogram skin cells
into stem cells) to generate human DRG - type sensory neurons from ordinary skin cells called
fibroblasts.
Following a cut to the skin,
fibroblast cells rush to the wound and secrete a matrix that helps skin cells move
into place, grow, and heal the injury.
In 1963 Pietro Angeletti and one of us (Levi Montalcini), who were then at the Istituto Superiore di Sanità in Rome, dissected sensory and sympathetic ganglia
into their cellular components: neurons, glial cells (which support and nourish the neurons) and
fibroblasts (embryonic connective - tissue cells).
Indeed, they were: According to the team's findings, adipose stem cells can be turned
into iPS cells twice as quickly as
fibroblast skin cells and with 20 times the efficiency.
The potential of iPS cells to help treat everything from damaged heart tissue to Parkinson's disease, has prompted intensive research that has looked
into the use of skin
fibroblast cells as an alternative to controversial embryonic stem cells.
In this study, published in Nature 2010, Vierbuchen and colleagues showed that
fibroblasts can be converted
into neurons by false expression of defined transcription factors.
Human embryonic stem cells derived from affected embryos during a pre-implantation diagnostic (PGD), as well as the conversion of somatic cells, such as skin
fibroblasts,
into induced pluripotent stem cells by genetic manipulation, offer the unique opportunity to have access to a large spectrum of disease - specific cell models.
It has recently been demonstrated that mouse and human
fibroblasts can be reprogrammed
into an embryonic stem cell - like state by introducing combinations of four transcription factors.
Nectin - 1 / HveC mediates herpes simplex virus type - 1 entry
into primary human sensory neurons and
fibroblasts.
Review conceptual and technical aspects of direct reprogramming of somatic cells, such as
fibroblasts and astrocytes,
into induced neurons.