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.

The World Health Organization (WHO) has created a new Web site to help researchers, doctors and
patients obtain reliable information on high-quality clinical trials. Now you can go to one website and search all registers to identify clinical trial research underway around the world!

Disclaimer: The Visible Embryo web site is provided for your general information only. The information contained on this site should not be treated as a substitute for medical, legal or other professional advice. Neither is The Visible Embryo responsible or liable for the contents of any websites of third parties which are listed on this site.

Content protected under a Creative Commons License.

No dirivative works may be made or used for commercial purposes.

CLICK ON weeks 0 - 40 and follow along every 2 weeks of fetal development

There are many nuanced differences in pluripotent states of stem cells. By subjecting stem cells
to various influences, then analyzing each individual cell's reaction, a CODE was found.
Image Credit: Harvard's Wyss Institute

By analyzing the genetic makeup of individual stem cells, scientists have identified new ways to regulate and control their growth into various stem cell types.

Stem cells offer great potential in biomedical engineering due to their pluripotency, which is their ability to multiply indefinitely as well as differentiate into hundreds of different cells types in the body. But the complexity of how stem cells develop, how they are regulated through states of cellular change has been difficult to pinpoint — until now.

By using powerful new single–cell genetic profiling techniques, scientists at the Wyss Institute for Biologically Inspired Engineering and Boston Children's Hospital have uncovered far more variation in pluripotent stem cells than previously understood. The findings, reported in Nature, brings research closer to stem cells being leveraged for disease therapy and regenerative treatments.

"Stem cell colonies contain a lot of variability between individual cells. This has been considered problematic to developing predictive approaches to engineering stem cells. Now, we have discovered this variability could actually be beneficial to our ability to precisely control stem cells.

The team has learned that there are many small fluctuations in the state of a stem cell's pluripotency that can influence which developmental path it will follow. "We've captured a detailed molecular profile of the different states of stem cells," said George Daley, study co–senior author, Director of Stem Cell Transplantation at Boston Children's Hospital and a Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School.

Taking this into account, researchers are now better equipped to manipulate and precisely control which cell and tissue types will develop from an individual pluripotent stem cell or a colony of stem cells.

Researchers explored the developmental landscape of pluripotent stem cells by altering them with different chemicals, culture environments, and gene knockouts. Next, they analyzed the genetic makeup of each cell to observe any micro–fluctuations in that cell's state of pluripotency. They observed many small nuances in the way stem cells respond to internal, chemical and environmental cues. These cues revealed a complex circuit of "decision making" by developmental regulators.

Researchers now believe there is a stem cell "code" relating patterns of behavior in regulatory circuits to developmental outcomes. By manipulating that code, they hope to precisely output a specific cell state and create stem cell types patients are unable to produce on their own.

"The ability to understand and program stem cells throughout changing states of pluripotency is a critical necessity for the success of regenerative medicine. By making stem cell engineering more predictive, we hope to leverage the versatility of controllable pluripotent stem cells to address a wide range of diseases and injuries."

Donald Ingber PhD, Wyss Institute Founding Director, also Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital, and Professor of Bioengineering at the Harvard School of Engineering and Applied Sciences.

Abstract
Pluripotent stem cells (PSCs) are capable of dynamic interconversion between distinct substates; however, the regulatory circuits specifying these states and enabling transitions between them are not well understood. Here we set out to characterize transcriptional heterogeneity in mouse PSCs by single-cell expression profiling under different chemical and genetic perturbations. Signalling factors and developmental regulators show highly variable expression, with expression states for some variable genes heritable through multiple cell divisions. Expression variability and population heterogeneity can be influenced by perturbation of signalling pathways and chromatin regulators. Notably, either removal of mature microRNAs or pharmacological blockage of signalling pathways drives PSCs into a low-noise ground state characterized by a reconfigured pluripotency network, enhanced self-renewal and a distinct chromatin state, an effect mediated by opposing microRNA families acting on the Myc/Lin28/let-7 axis. These data provide insight into the nature of transcriptional heterogeneity in PSCs.

The Wyss Institute for Biologically Inspired Engineering at Harvard University (http://wyss.harvard.edu) uses Nature's design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world. Working as an alliance among all of Harvard's Schools, and in partnership with Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Boston Children's Hospital, Dana–Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Boston University, Tufts University, and Charité - Universitätsmedizin Berlin, University of Zurich and Massachusetts Institute of Technology, the Institute crosses disciplinary and institutional barriers to engage in high-risk research that leads to transformative technological breakthroughs. By emulating Nature's principles for self-organizing and self-regulating, Wyss researchers are developing innovative new engineering solutions for healthcare, energy, architecture, robotics, and manufacturing. These technologies are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and new start-ups.