The Niche

So many papers, so little time

Here are descriptions of papers that caught my eye over the last couple weeks. Some of these will be covered in more depth over the next week or two as research highlights. I’ll make a list of those later in the week.

Stem cells need special cell-cycling protein; amino acid makes mESC grow speedily

Harvard’s Piotr Sicinski finds that fibroblasts can proliferate just fine without cyclin A (they compensate with another cyclin, cyclin E). However, both hematopoietic and embryonic stem cells get stuck in the cell cycle. Cyclins are the regulatory subunits of a class of kinases that regulate cell division.

(See the paper in Cell Cyclin A is redundant in fibroblasts but essential in hematopoietic and embryonic stem cells. )

Steven McKnight at the University of Texas Southwestern Medical Center found that cultured mouse embryonic stem cells were making lots and lots of threonine dehydrogenase an enzyme necessary for breaking down the amino acid threonine, essential for energy production in the mitochondria. The researchers tried growing ES cells in different culture media, each lacking one of the 20 amino acids. The mouse ES cells were just fine, except when threonine was missing. (After 36 hours, all of the other cultures had about 1000 colonies; the one lacking threonine had less than 50!) In contrast, human cells seem to lack a functioning gene for threonine dehydrogrenase. And as anyone who has worked on both mouse and human cells will tell you, human cells are SLOOOOW. Maybe, just maybe, the researchers speculate, activating the gene in human cells can make their doubling just a big more speedy.

(See the paper in Science Dependence of mouse embryonic stem cells on threonine catabolism .)

New and better bone-makers

Circulating blood cells seem able to home to injury and form new bone in both humans and animals, according to work published in Stem Cells by Robert Pignolo at the University of Pennsylvania, College of Medicine.

(See Circulating Osteogenic Precursor Cells in Heterotopic Bone Formation.)

Also, some sources of cells are better than others when it comes to growing bone for tissue replacement. In Nature Materials, Molly Stevens and colleagues at Imperial College London report that bone made by the normal bone-forming cells found in adults produce strong bone nodules, normal in terms of its mineral composition. In contrast, the bone made from cells differentiated from embryonic stem cells is more like bone that is weakened with age. (See Comparative materials differences revealed in engineered bone as a function of cell-specific differentiation)

Cancer spawns in a latent niche

Working in the worm C. elegans, researchers led by Jane Hubbard at the New York University School of Medicine, find that differentiated cells that normally have no contact with stem cells can, under the wrong circumstances, allow the wrong cells to self-renew and proliferate. This works through aberrant signaling of that ubiquitous protein Notch and need not require genetic changes to sustain itself. (See A “latent niche” mechanism for tumor initiation in PNAS.)

Leukemia cells say ‘don’t eat me’ to the immune system

Stanford’s Irv Weissman has two papers in Cell The show that the marker CD47 is transiently activated in hematopoietic stem cells constitutively on in mouse cell leukemias and also that CD47 is an adverse prognostic factor in human malignancies.

Bioengineered tooth really works

Takashi Tsuji of the Tokyo University of Science and colleagues had combined mesenchymal stem cells and epithelial cells into “tooth germ”. Transplnated into a mouse, it developed into a tooth that really chews. The researchers, affiliated with the company Organ Technologies, says it is a harbinger for more functional bioengineered organs. (See Fully functional bioengineered tooth replacement as organ therapy in PNAS)


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