New Worlds: Family tree for cells

It has long been believed that female mammals – including humans – are born with all the eggs they need to reproduce during their lifetimes. But some claim that the female mammal’s egg supply is renewed over her adult lifetime and that the source of these eggs is stem cells that originate in the bone marrow.

Now, Weizmann Institute scientists have reached scientific conclusions about the claims by using an original method for reconstructing lineage trees for cells. Their work was published recently in PLoS Genetics.

The method, developed over several years in the lab of Prof. Ehud Shapiro of the Rehovot institute’s departments of biological chemistry, computer science and applied mathematics, uses mutations in specific genetic markers to determine which cells are most closely related and how far back they share a common parent cell, to create a sort of “family tree” for cells.

Shapiro and members of his lab, including Drs. Shalev Itzkovitz and Rivka Adar, together with Prof. Nava Dekel and research student Yitzhak Reizel of the biological regulation department, used their method to see if ova could be descended from bone-marrow stem cells. Their findings, reached in cooperation with colleagues from Tel Aviv University and the Technion-Israel Institute of Technology in Haifa, indicated that any relationship between the two types was too distant for one to be an ancestor of the other.

These scientists also found, surprisingly, that the ova of older mice had undergone more cell divisions than those of younger mice. This could be the result of replenishment during adulthood, but an alternate theory holds that all eggs are created before birth, and those that undergo fewer divisions are simply selected earlier on for ovulation. Further experimentation, says Shapiro, will resolve the issue.

Cell “lineage trees” are similar to modern evolutionary and taxonomic “trees” based on genome comparisons between organisms.

Shapiro and his team used mutations in cells that are passed on to daughter cells over an organism’s lifetime (though not on to the next generation). By comparing a number of genetic sequences called microsatellites – areas where mutations occur like clockwork – they can place cells on trees to reveal their developmental history.

A number of papers published in recent months by Shapiro, his team and collaborators have demonstrated the power and versatility of this method. One study, for instance, lent support to the notion that the adult stem cells residing in tiny crypts in the lining of the colon do not harbor, as thought, “immortal DNA strands.” Immortal strands may be retained by dividing stem cells if they always relegate the newly-synthesized DNA to the differentiating daughter cell and keep the original stand in the one that remains a stem cell. A second study addressed an open question about developing muscle cells. Here they found that two kinds of progenitor cell – myogenic cells, which eventually give rise to muscle fiber, and non-myogenic cells found within the same muscle – are more closely related than similar cells in different muscles.

One immediate advantage of the cell lineage analysis method developed by Shapiro’s team is that it is non-invasive and retrospective and thus can be applied to the study of human cell lineages. Most other studies of development rely on genetically engineered lab animals in which the stem cells are tagged with fluorescent markers. Not only does it provide a powerful new research method that doesn’t rely on such markers, but Shapiro believes it could one day be used as a diagnostic tool that might, for instance, reveal the history of an individual’s cancer and help doctors determine the best course of treatment.

ANCIENT WRITINGS TO STUDY CLIMATE CHANGE

Reconstructing climates from the past provides historical comparison to modern weather events and valuable context for climate change. In the natural world, trees, ice cores and coral provide evidence of past weather, but from human sources scientists are limited by the historical information available. Until now, researchers have relied on official records detailing weather patterns, including air force reports from World War II and 18th-century ships’ logs. Now, ancient manuscripts written by Arabic scholars are believed to provide valuable meteorological information to help modern scientists reconstruct the climate of the past, a new study published in the Weather journal has found. Spanish scientists from the University of Extremadura have analyzed the writings of scholars, historians and diarists in Iraq from the Islamic Golden Age between 816 and 1009 CE for evidence of abnormal weather patterns.

Arabic documentary sources – historians and “political commentators” – from the ninth and 10th centuries focus on the social and religious events of the time but do refer to abnormal weather events.

“Climate information recovered from these ancient sources mainly refers to extreme events which impacted wider society, such as droughts and floods,” said lead author Dr. Fernando Domínguez-Castro. “However, they also document conditions that were rarely experienced in ancient Baghdad, such as hailstorms, the freezing of rivers or even cases of snow.”

Baghdad was a center for trade, commerce and science in the ancient Islamic world. In 891 CE, Berber geographer al-Ya’qubi wrote that the city had no rival in the world, with hot summers and cold winters, climatic conditions that favored strong agriculture.