The Pluripotent

The reprogramming field seems to be moving oh-so-fast.  First authorJian-Chien Dominic Heng (Genome Institute of Singapore) and colleagues in Singapore and Boston have discovered that a nuclear receptor known as Nr5a2 or Lrh-1 can replace Oct4, a critical transcription factor thought to be needed for generating induced pluripotent stem (iPS) cells.  This discovery adds another question to the current putative models to what molecular mechanisms are involved when a somatic cell is reprogrammed the the pluripotent state. It’s possible that Nr5a2, which has a multitude of biological functions,  has similar functions or binding sites as Oct4.  It’s also possible that Nr5a2 a direct target of Oct4 and has always been a critical factor in the reprogramming program. Nr5a2, who are you?

Here’s the abstract:

Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) with the introduction of Oct4, Sox2, Klf4, and c-Myc. Among these four factors, Oct4 is critical in inducing pluripotency because no transcription factor can substitute for Oct4, whereas Sox2, Klf4, and c-Myc can be replaced by other factors. Here we show that the orphan nuclear receptor Nr5a2 (also known as Lrh-1) can replace Oct4 in the derivation of iPSCs from mouse somatic cells, and it can also enhance reprogramming efficiency. Sumoylation mutants of Nr5a2 with enhanced transcriptional activity can further increase reprogramming efficiency. Genome-wide location analysis reveals that Nr5a2 shares many common gene targets with Sox2 and Klf4, which suggests that the transcription factor trio works in concert to mediate reprogramming. We also show that Nr5a2 works in part through activating Nanog. Together, we show that unrelated transcription factors can replace Oct4 and uncovers an exogenous Oct4-free reprogramming code.

Have access to Cell Stem Cell? Get the paper here.

Popularity: 10% [?]

3 million doses of the H1N1 or Swine Flu vaccines will be available to the public beginning the first week of October. Most of the doses will be a nasal spray type not recommended for those pregnant,over the age of 50, or those with asthma and other health problems. However injections will be arriving one to two weeks after the release of the nasal spray.

Health officials originally debated whether to wait and amass a larger stock of vaccines or to disperse smaller quantities and chose the latter. A factor may be the “widespread flu activity in 21 states”, which are testing positive as strains of the new H1N1 virus. The vaccine that is coming out next month immunizes against this new strain, but seasonal vaccines also contain a H1N1 component that is a different strain of the H1N1. Consequently there may be two different strains of the H1N1 virus circulating and being treated by two different shots.

Because the nasal sprays will be in limited supply, it will be decided locally who can get those first, so contact your doctor for more details.

via [NYT]

Popularity: 10% [?]

Research led by Dr. Steven McKnight of UT Southwestern Medical Center has demonstrated that the activation of a particular gene encoding threonine dehydrogenase (TDH) may be a key component of why mouse embryonic stem cells are easily grown in a laboratory while other mammalian ES cells are difficult, if not impossible, to maintain.

Here’s the abstract:

Measurements of the abundance of common metabolites in cultured embryonic stem (ES) cells revealed an unusual state with respect to one-carbon metabolism. These findings led to the discovery of copious expression of the gene encoding threonine dehydrogenase (TDH) in ES cells. TDH-mediated catabolism of threonine takes place in mitochondria to generate glycine and acetyl-CoA, with glycine facilitating one-carbon metabolism via the glycine cleavage system and acetyl-CoA feeding the tricarboxcylic acid (TCA) cycle. Culture media individually deprived of each of the 20 amino acids were applied to ES cells, leading to the discovery that ES cells are critically dependent upon but one amino acid—threonine. These observations show that ES cells exist in a unique, high-flux backbone metabolic state comparable to that of rapidly growing bacterial cells.

Get the full text here (with access).

Popularity: 14% [?]

Robert Klein, the chariman of CIRM, will not seek a new term when his six-year term ends at the end of 2010.  Klein has been criticized for mainly two things: (1) Proposition 71, which was proposed by him and approved by California voters to use a state-bond supported plan to fund stem cell research, and (2) his request for a $150,000 salary at the time when California is facing a multibillion-dollar budget deficit.  Despite the bad timing, was it too much to ask after working gratis for five years?  Get ready my popcorn and nachos, waiting for the scene when Bob Klein dumps CIRM, CIRM gets all cried out, and begs her man back.

Popularity: 14% [?]

The Anatomy of A Silent Crisis

It cannot be denied that global warming has made its presence more visible each year. The rise in temperatures   threaten the lifestyles of not only animals but humans as well.  As animals are forced to adapt to changing habitats, only the most adaptable will survive. This applies to humans as well.  The simple rise in temperature has acted as a domino effect in which the consequences are being discovered daily.

Most recently it has been reported that this climate change has led to  300,000 deaths and about $125 billion in economic losses as reported by the Global Humanitarian Forum. Along with the deaths, the report said that the lives of 325 million people, primarily in poor countries, were being seriously affected by climate change. It projected that the number would double by 2030. Although a few experts question the methodology and conclusion of the report, the Global Humanitarian Forum defends their report by saying that it serves merely as an estimate. Its real goal seems to be is to draw political and public awareness to a rising problem.

Although global warming has played a part in the economies of these denizens, this report has brought to light the more apparent need. The need to accommodate governmental policies  in order to reduce the vulnerability in dealing with global warming. We are the ones who need to adapt in order to be those that can survive.

via [NYT]

Popularity: 18% [?]

Hwang Woo-suk’s Sooam Biotech Research Center has claimed they have for the first time created cloned pig embryos and used them to make embryonic stem-cell lines.  If you’ve been living in a cave (or a lab) during 2004, Hwang is the man who claimed to have succeeded in cloning human embryos by nuclear transfer.  After much excitement for his alleged results, it all turned about to be quacky, sending Hwang’s reputation down to hell.

Hyun Sang-hwan, Hwang’s key colleague at Sooam, told The Korea Times that the study will be reported in Zygote, a peer-review journal published by Cambridge University, in two or three months. Hyun also said the study on cloned pig stem cells will mark the starting point of Hwang’s comeback.

Let’s just see how reproducible the data will be.

[Via The Korea Times]

Popularity: 12% [?]

Anjali Nayar reports that a gene on the extra chromosome that causes Down’s syndrome helps to protect those with the disorder from some types of cancer. Sandra Ryeom, a vascular biologist at Children’s Hospital Boston in Massachusetts, and her colleagues experimented with mice and with human cells to show that an additional third copy of the DSCR1 gene (also known as RCAN1) can suppress the growth of the blood vessels that feed cancerous tumours.  The paper by Baek, K.-H. et al. is in Nature’s advance online publication.

[Via Nature]

Popularity: 24% [?]

Besides clenching my teeth at the thought of writing up another organic chemistry lab report, here’s another reason I’m not a chemist.  A UCLA chemistry research assistant was withdrawing t-butyllithium from a container when a syringe malfunctioned, splashing her with the highly flammable solution. She wasn’t wearing a protective lab coat, and suffered extensive burns from the chemical, which ignites on contact with air.  She was critically burned and died on Jan 6.

The California Division of Occupational Safety and Health fined the university nearly $32,000.  UCLA was cited for failing to train personnel in the use of dangerous chemicals, for not requiring the wearing of protective clothing and for not correcting the deficient lab practices identified in an inspection last October.

Only $32,000?  Safety and Health might as well have told UCLA “The university’s fatal wrongdoing is worth a Toyota.”

[Via Nature]

Popularity: 24% [?]

What’s that thing I vaguely remember Warren Buffet saying something about buying stocks and something about fear? Oh right… buy up when fear is sending stock prices to plunge. “Be fearful when others are greedy, and be greedy when others are fearful.”  While the fear of the global economic downturn it causing the stock market to plummet, it’s time for you to think about that rich man’s sound bite.  So here are the top three stem cell stocks under what you pay for a Big Mac meal.

#1: Aastrom Biosciences, Inc. (NASDAQ:ASTM)

Aastrom develops products for the repair or regeneration of human tissue.  Aastrom’s proprietary Tissue Repair Cell (TRC) technology involves autologous (meaning the patient’s own), mixed-cell products containing stem and early progenitor cells to treat cardiac and vascular tissue regeneration.

The Reason: The current market conditions have battered down stocks like this micro cap. But with the increased interest in stem cell research, federal grant money coming, and a treatment that — if it works — could change the lives of millions.

#2: Curis, Inc. (NASDAQ:CRIS)

Located in Cambridge, Massachusetts, Curis develops drugs primarily for cancer treatment. They target signaling pathway technologies on a molecular level.

The Reason:  Curis has a bunch of drugs in phase I and II clinical trials.  According to sources, Curis is gaining solid financial footing.  Caveat emptor, but for the first quarter of 2009, the company reported a net income of $1.1 million. Compare that to Q1 2008 when it saw a net loss of $3.4 million.

#3: Sangamo Biosciences Inc. (NASDAQ:SGMO)

Sangamo’s ZFP TF technology allows researchers to target individual genes and work at turning them on and off.

The Reason:  Sangamo has a pipeline of incredible research and potential products. Competitors are willing to pay extraordinary amounts to get their hands on its technologies. And the company is in a strong financial position.

Take the jump for recommended shares.

[Via TFN]

Popularity: 6% [?]

Here’s some exciting news regarding hematopoietic stem cell development coming from Boston (The Pluripotent headquarters).  Two studies by Leonard Zon’s and George Daley’s groups have supported the following hypothesis:  A beating heart and blood flow are necessary for development of the blood system, which relies on mechanical stresses to cue its formation.

Zon and colleagues found that compounds that modulate blood flow had a potent impact on the expression of a Runx1, a master regulator of blood formation.  Runx1 is also a recognized marker for the blood stem cells that give rise to all the cell types in the blood system.  They also observed that a strain of mutant embryos that lacked a heartbeat and blood circulation exhibited severely reduced numbers of blood stem cells.  And the key biochemical regulator that was in charge of all this?  Nitric oxide!  Increasing nitric oxide in the blood of mutant embryos rescued blood stem cell production.

Daley and colleagues discovered that just the stress and biomechanical forces on the lining of blood vessels were able to increase the production of progenitor cells that gave rise to blood cells.

The report by Children’s Hospital says “the authors of the two papers speculate that drugs that mimic the effects of embryonic blood flow on blood precursor cells, or molecules involved in nitric oxide signaling, might be therapeutically beneficial for patients with blood diseases. For example, nitric oxide could be used to grow and expand blood stem cells either in the culture dish or in patients after transplantation.”

Anyone up for testing nitric oxide for blood doping?  On second thought, please don’t try it.

Abstracts:

Zon:

During vertebrate embryogenesis, hematopoietic stem cells (HSCs) arise in the aorta-gonads-mesonephros (AGM) region. We report here that blood flow is a conserved regulator of HSC formation. In zebrafish, chemical blood flow modulators regulated HSC development, and silent heart (sih) embryos, lacking a heartbeat and blood circulation, exhibited severely reduced HSCs. Flow-modifying compounds primarily affected HSC induction after the onset of heartbeat; however, nitric oxide (NO) donors regulated HSC number even when treatment occurred before the initiation of circulation, and rescued HSCs in sih mutants. Morpholino knockdown of nos1 (nnos/enos) blocked HSC development, and its requirement was shown to be cell autonomous. In the mouse, Nos3 (eNos) was expressed in HSCs in the AGM. Intrauterine Nos inhibition or embryonic Nos3 deficiency resulted in a reduction of hematopoietic clusters and transplantable murine HSCs. This work links blood flow to AGM hematopoiesis and identifies NO as a conserved downstream regulator of HSC development.

Full text

Daley:

Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system^{1, 2}. After initiation of the heartbeat in vertebrates, cells lining the ventral aspect of the dorsal aorta, the placental vessels, and the umbilical and vitelline arteries initiate expression of the transcription factor Runx1 (refs 3–5), a master regulator of haematopoiesis, and give rise to haematopoietic cells⁴. It remains unknown whether the biomechanical forces imposed on the vascular wall at this developmental stage act as a determinant of haematopoietic potential⁶. Here, using mouse embryonic stem cells differentiated in vitro, we show that fluid shear stress increases the expression of Runx1 in CD41⁺c-Kit⁺ haematopoietic progenitor cells⁷, concomitantly augmenting their haematopoietic colony-forming potential. Moreover, we find that shear stress increases haematopoietic colony-forming potential and expression of haematopoietic markers in the para-aortic splanchnopleura/aorta–gonads–mesonephros of mouse embryos and that abrogation of nitric oxide, a mediator of shear-stress-induced signalling⁸, compromises haematopoietic potential in vitro and in vivo. Collectively, these data reveal a critical role for biomechanical forces in haematopoietic development.

Full text

[Via CHB]

Popularity: 10% [?]