Ten most talked about articles in Cell magazine (November)

Founded in 1976, Cell has now become one of the most famous journals in the field of natural science research in the world, and has published more than a dozen sister journals, occupying a pivotal position in their respective professional fields. Cell mainly publishes important and original scientific research reports, and many of the most important discoveries in life sciences are published on Cell. The top ten download papers of "Cell" this month are:

1. Revisiting Global Gene Expression Analysis

Jakob Lovén, David A. Orlando, Alla A. Sigova, Charles Y. Lin, Peter B. Rahl, Christopher B. Burge, David L. Levens, Tong Ihn Lee, Richard A. Young

Researchers from the Whitehead Institute of Massachusetts Institute of Technology in the United States reported that in many current and diverse biological studies, common assumptions used to generate and understand global gene expression analysis data can lead to severe Defective conclusion.

Most of today's understanding of gene expression data relies on the assumption that all cells used for analysis have a similar total amount of mRNA, where mRNA accounts for approximately 10% of cellular RNA, and serves as a blueprint for protein synthesis. However, some cells, including malignant cancer cells, produce several times more mRNA than others. Traditional global gene expression analysis usually ignores these differences.

The researchers recently revealed this defect when studying the gene expression of cancer cells expressing high levels of c-Myc. It is known that c-My is a gene regulator and is highly expressed in malignant cancer cells. When comparing cells expressing high levels of c-Myc with cells expressing low levels of c-Myc, they were surprised to find that different gene expression analysis methods can produce significantly different results. Further research revealed that there are significant differences between cells containing high levels of c-Myc and low levels of c-Myc, but these differences are masked by commonly used experimental and analytical methods.

2. Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors

Kazutoshi Takahashi, Shinya Yamanaka

This is the representative work of this year ’s Nobel Prize in Physiology / Medical Medicine Yamanaka Yamanaka. In this paper, Yamanaka Yamanaka and others first used four stem cell transcription factors OCT4, SOX2, KLF4 and c-MYC to reprogram mice through somatic cell reprogramming. Fibroblasts are transformed into iPS cells with the characteristics of embryonic stem cells. This is the result of successive research on iPS.

3. Hallmarks of Cancer: The Next Generation

Douglas Hanahan, Robert A. Weinberg

The veteran star thesis has been listed on the list countless times,

The latest cancer review completed by Robert A. Weinberg is an upgraded version of his previous article "The Hallmarks of Cancer"-the previous article introduced the six basic characteristics of tumor cells, known as tumors So far, this classic paper has been cited tens of thousands of times.

In March 2011, Robert A. Weinberg also collaborated with Douglas Hanahan to complete a 29-page paper that outlined the hotspots and progress in oncology in the past 10 years, including autophagy, tumor stem cells, and tumor microenvironment And so on, and expanded the six characteristics of the original tumor cells to ten, these ten characteristics are:

Self-Sufficiency in Growth Signals; Insensitivity to Antigrowth Signals; Resisting Cell Death; Limitless Replicative Potential; Continuous Angiogenesis (Sustained Angiogenesis); Tissue Invasion and Metastasis; Avoiding Immune Destruction; Tumor Promotion Inflammation; Deregulating Cellular Energetics; Genomic Instability and Mutations ( Genome Instability and Mutation).

4. Activation of Innate Immunity Is Required for Efficient Nuclear Reprogramming

Jieun Lee, Nazish Sayed, Arwen Hunter, Kin Fai Au, Wing H. Wong, Edward S. Mocarski, Renee Reijo Pera, Eduard Yakubov, John P. Cooke

The facts tell us that urgency changes, and when threatened, there will be a flexible turnaround. This principle may explain why scientists think of viruses in the experiments of reprogramming somatic cells. This research team from the United States reported that the defensive response of cells to viruses may make it easier to express genes that are normally turned off. ——Including genes that turn on inflammation or become active during the state of stem cells. This discovery helps scientists better understand cell reprogramming and can also be used to develop more efficient and safe methods of reprogramming cells.

Although the somatic cell reprogramming technology won this year's Nobel Prize in Physiology / Medical, the actual details of this process are still a mystery.

This research technique, first reported by Yamanaka Yamanaka in 2006, was originally implemented using four key factors, which were transferred to the genome of the host cell through retroviral infection. We know very little about this process, we What is known is that the proteins encoded by these genes start a series of cascading amplification effects, reprogramming mature cells into pluripotent cells. This process is called the induced pluripotent stem cell iPS process, which helps scientists to obtain the same Matching cell lines to study disease in a completely new way, and this technology may one day be used in regenerative medicine.

However, an important drawback of the first reprogramming cell technology is that the viral insertion genes present in iPS cells are carcinogenic. Although scientists have found several ways to achieve reprogramming without permanently changing the genome, The effect is not ideal, and more new methods need to be found.

One of the particularly attractive methods is to use protein for reprogramming, which can completely avoid the use of foreign genes. Scientists can directly insert proteins to achieve related cascade amplification, but in this latest research Previously, this process was very inefficient.

John Cooke of Stanford University School of Medicine and others hope to understand why these proteins work poorly. They carefully analyzed when using a single reprogramming factor (a gene in a retrovirus, or a protein that can pass through the cell membrane) for reprogramming The event occurred at the time, the results show that in these two cases, the former can trigger a downstream cascade reaction within a few hours, while the latter takes several days.

This method of transflammation can help researchers find a way to directly transform one mature cell into another, completely skipping the pluripotent state.

5. Retraction Notice to: Elevated tRNAiMet Synthesis Can Drive Cell Proliferation and Oncogenic Transformation

Lynne Marshall, Niall S. Kenneth, Robert J. White

6. Relative Mitochondrial Priming of Myeloblasts and Normal HSCs Determines Chemotherapeutic Success in AML

Thanh-Trang Vo, Jeremy Ryan, Ruben Carrasco, Donna Neuberg, Derrick J. Rossi, Richard M. Stone, Daniel J. DeAngelo, Mark G. Frattini, Anthony Letai

In a new study, researchers from the Dana-Farber Cancer Institute developed a new method to determine whether acute myeloid leukemia (AML) cells are in death-ready status. A discovery may help cancer experts choose more effective methods to treat patients with AML. They report that their findings may lead people to improve existing testing methods to predict which successfully treated AML patients use standard chemotherapy alone Can continue to alleviate the condition, which patients may suffer tumor recurrence even after receiving additional treatment, but may benefit from bone marrow transplantation treatment.

7. The Obligation for Biologists to Commit to Political Advocacy

Thomas D. Pollard

8. Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors

Kazutoshi Takahashi, Koji Tanabe, Mari Ohnuki, Megumi Narita, Tomoko Ichisaka, Kiichiro Tomoda, Shinya Yamanaka

In 2007, another important achievement of Yamanaka Yamanaka: Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors was also published in Cell magazine. In this article, he and Thomson Lab used retroviruses (retrovirus) respectively. After infecting human skin fibroblasts with 4 transcription factors OCT4, SOX2, c-MYC, KLF4 or OCT4, SOX2, LIN28 and NANOG with lentivirus vectors, they are transformed into human iPS cells with the characteristics of embryonic stem cells.

9. FOXP2 and Human Cognition

Philip Lieberman

10. Efficient Direct Reprogramming of Mature Amniotic Cells into Endothelial Cells by ETS Factors and TGFβ Suppression

Michael Ginsberg, Daylon James, Bi-Sen Ding, Daniel Nolan, Fuqiang Geng, Jason M. Butler, William Schachterle, Venkat R. Pulijaal, Susan Mathew, Stephen T. Chasen et al.

Researchers from Weill School of Medicine at Cornell University in the United States have developed a new method that can obtain a large number of circulatory system cells-vascular endothelial cells (VECs) from amniotic fluid cells (ACs). This research result was published on October 18 In the online version of the Japanese Cell magazine, the research results completed in mice will open a new way to establish a huge inventory of VECs needed for organ regeneration and treatment of various vascular diseases.

At present, there is no effective treatment for the vast number of patients with vascular diseases, including heart disease, stroke, lung disease, external trauma, emphysema, and even diabetes and nervous system diseases. Using normal cultured endothelial cells to replace damaged or dysfunctional endothelial cells, a new treatment method is proposed for the treatment of these millions of patients suffering from diseases worldwide.

Many vascular diseases stem from dysfunction of vascular endothelial cells, so implanting healthy cells in patients is an attractive treatment strategy. However, the past stem cell methods failed to meet the requirements: vascular endothelial cells differentiated from stem cells were unstable and often transformed into non-vascular cells, and these cells could not be rapidly expanded in number, which limits their clinical application. .

In order to overcome these problems, this research group has developed a safe new method to produce a large number of stable vascular endothelial cells from amniotic fluid cells. Amniotic fluid cells can be extracted through the conventional amniotic membrane puncture process, so it can be said to be a stable cell source . The researchers used 26 members of the Ets-twenty-six family of Ets proteins to open and Turned off some special genes-this family of transcription factors can bind to DNA, which is important for VEC development.

rAC-VECs are similar to human mature VECs and can express normal blood vessel-specific genes. When the researchers transplanted rAC-VECs into the regenerating liver of mice, they found that these cells formed stable, normal, functional blood vessels . This major breakthrough will help use endothelial cells to treat a variety of vascular diseases, and countless patients will benefit from it.

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