An indirect approach to generating specific human cell types

http://www.nature.com/nmeth/journal/v10/n1/full/nmeth.2325.html?WT.ec_id=NMETH-201301

Two groups derived neural and mesodermal cells from human fibroblasts by going through a partially reprogrammed intermediate.

Subject terms:

• Stem Cells
• Cell Biology
• Genetics

The ability to easily convert accessible human cells into disease-relevant cell types through cellular reprogramming has opened new doors for basic research and regenerative medicine¹. Takahashi and Yamanaka ushered in contemporary reprogramming when they demonstrated that a combination of four transcription factors (Oct3/4, Sox2, Klf4 and c-Myc) could drive skin-derived fibroblasts to a pluripotent state that could be further differentiated into the desired cell type² (Fig. 1a). But robust differentiation into specific lineages remains a stumbling block. Low efficiencies and week- to month-long protocols often give rise to mixed cultures requiring a second purification step. Purity matters, as remnant pluripotent cells can give rise to tumors after transplantation. Moreover, the yielded cells are typically immature (as in cardiomyocyte, hematopoietic or neuronal differentiation).

Tissue engineering: The brainmaker

With his knack for knowing what stem cells want, Yoshiki Sasai has grown an eye and parts of a brain in a dish.

'He' is Yoshiki Sasai, a stem-cell biologist at the RIKEN Center for Developmental Biology in Kobe, Japan. Sasai has impressed many researchers with his green-fingered talent for coaxing neural stem cells to grow into elaborate structures. As well as the optic cup¹, he has cultivated the delicate tissue layers of the cerebral cortex² and a rudimentary, hormone-making pituitary gland³. He is now well on the way to growing a cerebellum⁴ — the brain structure that coordinates movement and balance. “These papers make for the most addictive series of stem-cell papers in recent years,” says Luc Leyns, a stem-cell scientist at the Free University of Brussels.

And is tissue formation driven by a genetic program intrinsic to cells, or shaped by external cues from neighbouring tissues? By combining intuition with patient trial and error, Sasai has found that it takes a delicate balance of both: he concocts controlled environments that feed cells physical and chemical signals, but also gives them free rein to 'do their thing' and organize themselves into issues. He sometimes refers to himself as a Japanese matchmaker who knows that, having been brought together, two strangers need to be left alone. “They know what to do,” he says. “They interact in a delicate manner, and if the external cues are too strong, it will override the internal ones.”
  
http://www.nature.com/news/tissue-engineering-the-brainmaker-1.11232

The Histone Acetyltransferase MOF Is a Key Regulator of the Embryonic Stem Cell Core Transcriptional Network

Xiangzhi Li,1,2,6 Li Li,4,6 Ruchi Pandey,2 Jung S. Byun,5 Kevin Gardner,5 Zhaohui Qin,4 and Yali Dou2,3,*

www.ncbi.nlm.nih.gov/pubmed/22862943

Pluripotent embryonic stem cells (ESCs) maintain
self-renewal and the potential for rapid response to
differentiation cues. Both ESC features are subject
to epigenetic regulation. Here we show that the
histone acetyltransferase Mof plays an essential
role in the maintenance of ESC self-renewal and plu-
ripotency. ESCs with Mof deletion lose characteristic
morphology, alkaline phosphatase (AP) staining, and
differentiation potential. They also have aberrant
expression of the core transcription factors Nanog,
Oct4, and Sox2. Importantly, the phenotypes of Mof
null ESCs can be partially suppressed by Nanog
overexpression, supporting the idea that Mof func-
tions as an upstream regulator of Nanog in ESCs.
Genome-wide ChIP-sequencing and transcriptome
analyses further demonstrate that Mof is an integral
component of the ESC core transcriptional network
and that Mof primes genes for diverse develop-
mental programs. Mof is also required for Wdr5
recruitment and H3K4 methylation at key regulatory
loci, highlighting the complexity and interconnectiv-
ity of various chromatin regulators in ESCs.