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Today, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than 1 million visitors each month. The field of early embryology has grown to include the identification of the stem cell as not only critical to organogenesis in the embryo, but equally critical to organ function and repair in the adult human. The identification and understanding of genetic malfunction, inflammatory responses, and the progression in chronic disease, begins with a grounding in primary cellular and systemic functions manifested in the study of the early embryo.

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Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
CLICK ON weeks 0 - 40 and follow along every 2 weeks of fetal development
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Home | Pregnancy Timeline | News Alerts |News Archive Oct 23, 2013

 

Embryonic stem cell-like colonies are shown growing on microgrooved surfaces.
Staining shows cell nuclei in blue, and a pluripotent stem cell marker in green.
Image
Credit: Song Li Lab



Pluripotent stem cells, created from human skin or mouse ear tissue, are shown here becoming endoderm cells. The endoderm is one of the three primary germ layers that ultimately contribute to the development of vital organs (liver, pancreas, etc.).

Yellow highlights the Sox17 protein, expressed during endoderm development.
Cell nuclei are shown in magenta.  Image Credit: Song Li Lab

 







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Changing mature cells into embryonic-like stem cells

Bioengineers at the University of California, Berkeley, have shown that physical cues can replace certain chemicals when nudging mature cells back to a pluripotent stage, capable of becoming any cell type in the body.

The researchers grew fibroblasts cells taken from human skin and mouse ears on surfaces with parallel grooves measuring 10 micrometers wide and 3 micrometers high. After two weeks of culture in a special cocktail used to reprogram mature cells, the researchers found a four-fold increase in the number of cells that reverted back to an embryonic-like state compared with cells grown on a flat surface. Growing cells in scaffolds of nanofibers aligned in parallel had similar effects.

The study, published online Sunday, Oct. 20, in the journal Nature Materials, could significantly enhance the process of reprogramming adult cells into embryonic-like stem cells that can differentiate, or develop, into any type of tissue that makes up our bodies.

The 2012 Nobel Prize in Physiology or Medicine was awarded to scientists who discovered that it was possible to reprogram cells using biochemical compounds and proteins that regulate gene expression. These induced pluripotent stem cells have since become a research mainstay in regenerative medicine, disease modeling and drug screening.

"Our study demonstrates for the first time that the physical features of biomaterials can replace some of these biochemical factors and regulate the memory of a cell's identity," said study principal investigator Song Li, UC Berkeley professor of bioengineering. "We show that biophysical signals can be converted into intracellular chemical signals that coax cells to change."

The current process for reprogramming cells relies on a formula that uses a virus to introduce gene-altering proteins into mature cells. Certain chemical compounds, including valproic acid, that can dramatically affect global DNA structure and expression are also used to boost the efficiency of the reprogramming process.

"The concern with current methods is the low efficiency at which cells actually reprogram and the unpredictable long-term effects of certain imposed genetic or chemical manipulations," said study lead author Timothy Downing, who did this research as a graduate student in the UC Berkeley-UC San Francisco Joint Graduate Program in Bioengineering. "For instance, valproic acid is a potent chemical that drastically alters the cell's epigenetic state and can cause unintended changes inside the cell. Given this, many people have been looking at different ways to improve various aspects of the reprogramming process."

Previous studies have shown that physical and mechanical forces can influence cell fate, but the effect on epigenetic state and cell reprogramming had not been clear.

The new study found that culturing cells on micro-grooved biomaterials improved the quality and consistency of the reprogramming process, and was just as effective as valproic acid.


"Cells elongate, for example, as they migrate throughout the body. In the case of topography, where we control the elongation of a cell by controlling the physical microenvironment, we are able to more closely mimic what a cell would experience in its native physiological environment. In this regard, these physical cues are less invasive and artificial to the cell and therefore less likely to cause unintended side effects."

Timothy Downing, PhD, former graduate student, UC Berkeley-UC San Francisco Joint Graduate Program in Bioengineering, now a research scientist with Song Li, UC Berkeley professor of bioengineering.


Researchers are studying whether growing cells on grooved surfaces could eventually replace valproic acid and perhaps other chemical compounds in the reprogramming process.

"We are also studying whether biophysical factors could help reprogram cells into specific cell types, such as neurons," said Jennifer Soto, UC Berkeley graduate student in bioengineering and another co-author of the study.

Abstract
Biochemical factors can help reprogram somatic cells into pluripotent stem cells, yet the role of biophysical factors during reprogramming is unknown. Here, we show that biophysical cues, in the form of parallel microgrooves on the surface of cell-adhesive substrates, can replace the effects of small-molecule epigenetic modifiers and significantly improve reprogramming efficiency. The mechanism relies on the mechanomodulation of the cells’ epigenetic state. Specifically, decreased histone deacetylase activity and upregulation of the expression of WD repeat domain 5 (WDR5)—a subunit of H3 methyltranferase—by microgrooved surfaces lead to increased histone H3 acetylation and methylation. We also show that microtopography promotes a mesenchymal-to-epithelial transition in adult fibroblasts. Nanofibrous scaffolds with aligned fibre orientation produce effects similar to those produced by microgrooves, suggesting that changes in cell morphology may be responsible for modulation of the epigenetic state. These findings have important implications in cell biology and in the optimization of biomaterials for cell-engineering applications.

Funding from the California Institute of Regenerative Medicine and the National Institutes of Health helped support this research.

Original press releas:http://www.eurekalert.org/pub_releases/2013-10/embl-co101113.php