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Welcome to The Visible Embryo, a comprehensive educational resource on human development from conception to birth.

The Visible Embryo provides visual references for changes in fetal development throughout pregnancy and can be navigated via fetal development or maternal changes.

The National Institutes of Child Health and Human Development awarded Phase I and Phase II Small Business Innovative Research Grants to develop The Visible Embryo. Initally designed to evaluate the internet as a teaching tool for first year medical students, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than one million visitors each month.

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 Aug 2, 2013

 

DNA methylation

DNA molecule methylating at the two center cytosines. Methylation
plays an important role for epigenetic gene regulation in
development and disease. Image Credit:Wikipedia
.





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Reprogramming cells while improving their function

The enormous promise of regenerative medicine is matched by equally enormous challenges. But a new finding has the potential to improve both the safety and performance of reprogrammed cells.

The researchers' study, published in the journal Nature, found that an enzyme, activation-induced cytidine deaminase (AID), helps in the process that changes an adult human cell into an induced pluripotent stem cell (iPS cell). These iPS cells can then be developed into any kind of cell needed to therapeutically restore tissues and organs.

The finding settles an ongoing controversy regarding use of AID to reprogram cells, says the study's senior investigator, Dr. Todd Evans, vice chair for research and professor of cell and developmental biology in the Department of Surgery at Weill Cornell Medical College.

"The dispute was whether AID is required to make iPS cells, and we found that the enzyme does make reprogramming very efficient, although it is not absolutely necessary," says Dr. Evans, an internationally-recognized authority on regenerative medicine. "In fact, we plan to test if reprogramming iPS cells without AID may even be helpful."

One reason is that AID can cause genetic mutations that can lead to cancer.


AID is best known as a master regulator of antibody diversity in B cells, and in order to create varied types of beneficial antibodies, it routinely mutates antibody genes. But sometimes the process goes awry, resulting in development of B cell lymphoma.

"That leads us to believe that if you can reprogram cells without AID, it could reduce risk of potential mutations, and thus be safer."

Dr. Todd Evans, vice chair for research and professor of cell and developmental biology in the Department of Surgery at Weill Cornell Medical College.


iPS Cells Without AID Remember What They Once Were

In order to push a cell such as a fibroblast back to an iPS cell, the "epigenetic markers" that define the adult cell must be removed. Dr. Evans: "All cells of the body have the same genes, but they are used differently in different tissues. If an undifferentiated cell becomes a heart cell, somehow it has to lock in and stabilize that particular adult phenotype and not forget what it is."

One way this is accomplished is by placing a methyl group on top of specific genes to activate a new cell destination—such as to become a liver cell—usually switching the previous gene destination off. "We have known how these marks are put on genes, but we didn't know how they were taken off. This is the process of pushing an adult cell to revert back to a stem-cell-like state," Dr. Evans says.


Dr. Evans and his colleagues found that the AID (activation-induced cytidine deaminase) enzyme removes epigenetic markers.


They then created a mouse that did not produce AID to see if the animal's adult fibroblast cells could be pushed back to iPS cells. Surprisingly, they found that the cells at first seemed to want to reprogram even faster than normal cells, but most never fully reverted to a stem-cell-like state. Dr. Evans: "They eventually crashed and differentiated back into a fibroblast. What that meant is that they never cleared their memory of being a fibroblast cell. AID efficiently removes that epigenetic memory, smoothing the way for a cell to morph into an undifferentiated state."

But some of the mouse adult fibroblasts lacking AID—those that Dr. Evans says they "babysat"—did become iPS cells.

Despite the fact that reprogramming adult cells without AID is inefficient, the researchers say that the method may offer another advantage besides increased safety. Dr. Evans : "It might be useful to allow epigenetic memory to be retained. If you want to make new cardiac cells to repair a patient's heart, it might be better to start with a cardiac cell and push it to become an iPS cell, from which other cardiac cells could be made. If these cells remember they were cardiac cells, they might make a better heart cell than if they came from reprogrammed fibroblasts."

Abstract
The activation-induced cytidine deaminase (AID; also known as AICDA) enzyme is required for somatic hypermutation and class switch recombination at the immunoglobulin locus1. In germinal-centre B cells, AID is highly expressed, and has an inherent mutator activity that helps generate antibody diversity2. However, AID may also regulate gene expression epigenetically by directly deaminating 5-methylcytosine in concert with base-excision repair to exchange cytosine3. This pathway promotes gene demethylation, thereby removing epigenetic memory. For example, AID promotes active demethylation of the genome in primordial germ cells4. However, different studies have suggested either a requirement5 or a lack of function6 for AID in promoting pluripotency in somatic nuclei after fusion with embryonic stem cells. Here we tested directly whether AID regulates epigenetic memory by comparing the relative ability of cells lacking AID to reprogram from a differentiated murine cell type to an induced pluripotent stem cell. We show that Aid-null cells are transiently hyper-responsive to the reprogramming process. Although they initiate expression of pluripotency genes, they fail to stabilize in the pluripotent state. The genome of Aid-null cells remains hypermethylated in reprogramming cells, and hypermethylated genes associated with pluripotency fail to be stably upregulated, including many MYC target genes. Recent studies identified a late step of reprogramming associated with methylation status7, and implicated a secondary set of pluripotency network components8. AID regulates this late step, removing epigenetic memory to stabilize the pluripotent state.

The study was supported by National Institutes of Health grants (HL056182 and AI072194) and a National Science Foundation CAREER grant (1054964).

Other study co-authors include Ritu Kumar, Ting-Chun Liu, Philipp Franck and Olivier Elemento from Weill Cornell Medical College; Lauren DiMenna, Nadine Schrode, Silvia Muñoz-Descalzo, Anna-Katerina Hadjantonakis and Jayanta Chaudhuri from Memorial Sloan-Kettering Cancer Institute; and Ali A. Zarrin from Genentech.

The authors declare no competing financial interests.

Weill Cornell Medical College
Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit weill.cornell.edu.

Original press release:http://www.eurekalert.org/pub_releases/2013-08/wcmc-air080113.php