An in vivo study suggests that heterogeneous cell cultures block desired differentiation

by Mariano Loza Coll

It has not been easy to steer pluripotent cells toward making sperm in vitro. Learning how sperm precursors develop in vivo allowed a group led by Mitinori Saitou at RIKEN in Kobe, Japan, to derive embryonic primordial germ cells from embryonic cells in culture and use them to restore fertility in sterile mice1. The work suggests that the secret to making some differentiation programs work may lie in shielding precursor cells from inhibitory signals generated within heterogenous cell cultures.

by Simone Alves

Galphas is vital for engrafting of haematopoietic stem cells

Whether coming from a bone marrow transplant or a patient's own circulating blood, haematopoietic stem cells are remarkably good at finding their way back to the bone marrow niche. David Scadden and his colleagues at the Harvard Stem Cell Institute in Cambridge, Massachusetts, report that a G-protein known as Galphas is necessary to direct these cells to the niche1.

Galphas is essential during development. To be able to look at the effect of its absence, the group developed a chimeric mouse in which some cells in each tissue expressed the protein and some did not; the distribution of cells missing and expressing the protein should have been random. As expected, both types of cells contributed to fetal liver, skin and muscle. However, cells that were missing the protein were also missing in the bone marrow. Surprisingly, in vivo experiments showed that Galphas-/- cells had the same haematopoietic potential as their wild-type counterparts — they were simply unable to engraft in the bone marrow during development.

by Monya Baker

Nanoparticles coated with stem cells aid cell delivery

[Editor's note: It's not easy to assess a study's ramifications from press releases, three of which caught my eye this month. I asked Phil Schwartz, a neural stem cell expert at Children's Hospital of Orange County, California, to help me understand the gap between study and therapy. I also asked authors from each paper to respond. This article is one of three resulting from this process.]

Research summary by Nature Reports Stem Cells: One problem with cell transplantation is that cell transplants die. Bioscaffolding is a way to keep cells alive so that they can engraft and integrate. Researchers led by Michel Modo from King's College London made polymer particles that could be coated with neural stem cells.

by Simone Alves

MLL1 epigenetically regulates postnatal neural specification

New neurons arise in the brain throughout adulthood, but the mechanisms that maintain neurogenesis are poorly understood. By inducing a mutation that decreases the production of neurons in the young adult brain, researchers have recently established an essential role in neurogenesis for the gene-regulating enzyme known as methyltransferase MLL1. 

MLL1 is one of a family of chromatin-remodelling factors — that is, proteins that control whether cells' gene-reading machinery can physically access DNA. Researchers led by Arturo Alvarez-Buylla of the University of California, San Francisco, created transgenic mice in which the Mll1 gene is deleted in neural stem cells at specific time in development1. In addition to dramatically lowering post-natal neurogenesis, the absence of Mll1 also prevented normal migration of neuronal precursors causing immature cell types to accumulate in a region known as the subventricular zone.

Thoms Grafby Monya Baker

In the quest to switch one cell type to another, how far can tweaking transcription factors go? Thomas Graf, of the Centre for Genomic Regulation in Barcelona, is known for his work on converting one blood cell type to another. Monya Baker spoke to him about how this can be done — and why. How do you turn one cell type into another?

It's a matter of learning the changes in transcription factor networks that are instrumental in dictating cell fate. As cells develop away from each other, the transcription factor networks are more and more different, and we have to do more and more to turn one into the other.

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