Stem cell update

Chromatin signatures of pluripotent cell lines.Azuara V, Perry P, Sauer S, Spivakov M, Jorgensen HF, John RM, Gouti M, Casanova M, Warnes G, Merkenschlager M, Fisher AG. Nat Cell Biol. 2006 Mar 29; [Epub ahead of print]

Enhanced purification of fetal liver hematopoietic stem cells using SLAM family receptors. Kim I, He S, Yilmaz OH, Kiel MJ, Morrison SJ. Blood. 2006 Mar 28; [Epub ahead of print]
As low as 1 HSC of fetal liver was transplanted. One out of 7.7 transplants (13%), CD48-Sca1+Lin-Mac1+ (SLM) fetal live cells gave rise to long-term multilineage reconstitution in irradiated mice, while 1 out of every 8.9 (11%) CD48-Thy(low)Sca-1(+)lineage-Mac-1(+) fetal liver cells do so. With addition of CD150, CD150+CD48-SLM cells give rise to long-term multilineage reconstitution at frequency of 30-42%. Fetal liver HSC were also found in CD41- and CD244- population. SLAM family receptors CD150, CD244, and CD48 are therefore shown enrichment markers for fetal liver HSC. The authors also emphasized the role of SLAM family receptors in distinguishing "progenitors at different stages of the hematopoiesis hierarchy and enhance the purification of definitive HSCs from diverse contexts".
Interestingly, they were not detectably expressed by stem cells in the fetal or adult nervous system.
Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Ito K, Hirao A, Arai F, Takubo K, Matsuoka S, Miyamoto K, Ohmura M, Naka K, Hosokawa K, Ikeda Y, Suda T. Nat Med. 2006 Mar 26; [Epub ahead of print]
In vitro germline potential of stem cells derived from fetal porcine skin. Dyce PW, Wen L, Li J. Nat Cell Biol. 2006 Mar 26; [Epub ahead of print]

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Pay too much tax?

It's been known that postdoc awardee of National Research Service Awards (NRSAs) receive their payments as fellowship, subject to tax exempt. However, many universities erroneously collect social security tax on them. So take a closer look at your W2! Do you overpay your tax?

Nature career has more story about it.

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Nat Genet Jun

Content

Adler AS, M Lin, H Horlings, DSA Nuyten, MJ van de Vijver, HY Chang. (2006) Genetic regulators of large-scale transcriptional signatures in cancer. Nat Genet 38 (4): 421-430
By Chang group

Kissler S, P Stern, K Takahashi, K Hunter, LB Peterson, LS Wicker. (2006) In vivo RNA interference demonstrates a role for Nramp1 in modifying susceptibility to type 1 diabetes. Nat Genet 38 (4): 479-483
By Kissler group

Loh Y-H, Q Wu, J-L Chew, VB Vega, W Zhang, X Chen, G Bourque, J George, B Leong, J Liu, K-Y Wong, KW Sung, CWH Lee, X-D Zhao, K-P Chiu, L Lipovich, VA Kuznetsov, P Robson, LW Stanton, C-L Wei, Y Ruan, B Lim, H-H Ng. (2006) The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet 38 (4): 431-440
By Ruan and Ng groups

Wei CL, Q Wu, VB Vega, KP Chiu, P Ng, T Zhang, A Shahab, HC Yong, Y Fu, Z Weng, J Liu, XD Zhao, JL Chew, YL Lee, VA Kuznetsov, WK Sung, LD Miller, B Lim, ET Liu, Q Yu, HH Ng, Y Ruan. (2006) A global map of p53 transcription-factor binding sites in the human genome. Cell 124 (1): 207-19
By Ng and Ruan groups

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Stem cells in CELL

Stem cells and cancer: two faces of eve. Clarke MF, Fuller M.Cell. 2006 Mar 24;124(6):1111-5. PMID: 16564000 [PubMed - in process]
The first publication since Mike Clarke moved to Stanford.
Connecting cancer to the asymmetric division of stem cells. Wodarz A, Gonzalez C. Cell. 2006 Mar 24;124(6):1121-3. PMID: 16564003 [PubMed - in process]
Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells.Betschinger J, Mechtler K, Knoblich JA.
Cell. 2006 Mar 24;124(6):1241-53. PMID: 16564014 [PubMed - in process]
Stem cell research in Brazil: a difficult launch. Leite M. Cell. 2006 Mar 24;124(6):1107-9. PMID: 16563999 [PubMed - in process]

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Stem Cell in Adult Mouse Testes

Recently, Nature news featured a report on stem cell in adult mouse testes. The researchers used mice with GFP labeled stem cells, and isolated the 0.3% stem cells from testes. Those cells are of stem cell properties. Further work on human and corpses was planned and is being carried out.

Pluripotency of spermatogonial stem cells from adult mouse testis. Kaomei Guan, Karim Nayernia, Lars S. Maier, Stefan Wagner, Ralf Dressel3, Jae Ho Lee, Jessica Nolte, Frieder Wolf, Manyu Li, Wolfgang Engel and Gerd Hasenfuss. Nature advance online publication 24 March 2006 | doi:10.1038/nature04697; Received 21 November 2005; ; Accepted 7 March 2006.

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JC Nat Biotech 24 (3)

Nat Biotech 24 (3) March 2006 content

Pyle AD, LF Lock, PJ Donovan. (2006) Neurotrophins mediate human embryonic stem cell survival. Nat Biotech 24 (3): 344-350

Many growth factors promote growth or self-renewal of human Embryonic Stem Cells (hESC), including FGF2, BMP antagonist Noggins, and ones involved in Wnt/ -catenin and activin/TGF . Micro-array and SAGE data/screening suggest tropomyosin-related kinase (TRK) receptors present in hESC, and may contribute to the growth or self-renewal of hESC.

Peter Donovan group found TRK receptors were indeed expressed and functional in hESC. The ligands of those receptors, namely neurotrophins, promote colonal survival of hESC and also retain the pluri/multi-potency of hESC. While inhibition of those receptors function results in hESC apoptosis. Signal transduction analyses suggest neutrophins induce phosphorylation of TRK receptors through PI3K, but not MAPK pathway. The findings may help high throughput screening for important factors of hESC growth and differentiation, under influence of neutrophins.

Interestingly, PTEN of PI3K pathway has been proved important in maintenance of stem cell renewal ability, and may be involved in various tumorigenesis processes.
Paper of interest:

Chao MV. (2003) Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci 4 (4): 299-309

Patapoutian A, LF Reichardt. (2001) Trk receptors: mediators of neurotrophin action. Curr Opin Neurobiol 11 (3): 272-80

Richards M, SP Tan, JH Tan, WK Chan, A Bongso. (2004) The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells 22 (1): 51-64

Sato N, IM Sanjuan, M Heke, M Uchida, F Naef, AH Brivanlou. (2003) Molecular signature of human embryonic stem cells and its comparison with the mouse. Dev Biol 260 (2): 404-13

Herszfeld D, E Wolvetang, E Langton-Bunker, T-L Chung, AA Filipczyk, S Houssami, P Jamshidi, K Koh, AL Laslett, A Michalska, L Nguyen, BE Reubinoff, I Tellis, JM Auerbach, CJ Ording, LHJ Looijenga, MF Pera. (2006) CD30 is a survival factor and a biomarker for transformed human pluripotent stem cells. Nat Biotech 24 (3): 351-357

Genetic instabilities or cytogenetic abnormalities in hESC are acquired during in vitro propagation, and may contribute to the tumorigenesis in human. Cytogenetics was almost the only method used for the examination of those abnormalities. Martin Pera group recently identified CD30, a member of TNF receptor superfamily, presented in transformed hESC, but not normal ones. Expression of CD30 protects hESC from apoptosis.

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The scientist 20(3)

The scientist 20(3) content

First off, thanks to KS Powell, Susan Linquist of MIT and Whitehead answered questions on how to communicate science. One of her secrets is to write for laypersons,like first-year gaduate students, not just to absolute experts.

The best places for postdoc (the scientist magazine) just came out. Thirty-five top institutions in North America (NA) and outside of NA for postdoc were listed. Important factors for choose postdoc places were analized, both the most important and the least important. They also featured 15 top institutions in and outside of NA in detail.

Of note, Gladstone Inst/UCSF topped 2006 list, jumping from No. 22 of last year. Several fed inst or centers were ranked high, including NIDDK, USDA ARS, and NCI. Cancer research centers were also recognized by the postdoc, including Fred Hutchingson and Fox Chase.

Top 15 institutions /best places for postdoc in NA

1. The J. David Gladstones Institutes, San Francisco
   
2. Fred Hutchinson Cancer Research Center, Seattle
   
3. US Environmental Protection Agency, Research Triangle Park, NC
   
4. Emory University,Atlanta, GA
   
5. National Institute of Environmental Health Sciences, Research Triangle Park, NC
   
6. Fox Chase Cancer Center,Philadelphia
   
7. National Institute of Diabetes &Kidney Diseases, NIH, Bethesda, MD
   
8. Wadsworth Center, Albany, NY
   
9. Dalhousie University, Halifax, Nova Scotia
   
10. USDA Agricultural Research Service, Beltsville, MD
    
11. Woods Hole Oceanographic Institution, Woods Hole, MA
    
12. Boyce Thompson Institute for Plant Research, Ithaca, NY
    
13. National Cancer Institute, Bethesda, MD
    
14. Donald Danforth Plant Science Center, Saint Louis, MO
    
15. Vanderbilt University, Nashville, TN
    
16. Cornell University,Ithaca, NY
    
17. Harvard Medical School, Boston, MA
    
18. US Environmental Protection Agency, Cincinnati, OH
    
19. University of Alabama at Birmingham, AL
    
20. National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ
    
21. University of California, Davis
    
22. Duke University, Durham, NC
    
23. Medical College of Wisconsin, Milwaukee
    
24. Mayo Clinic, Rochester, MN
    
25. University of Illinois, Urbana
    
26. Massachusetts Institute of Technology, Cambridge
    
27. Rockefeller University,New York
    
28. Washington University,Saint Louis, MO
    
29. The University of Texas M.D. Anderson Cancer Center,Houston
    
30. National Institutes of Health,Bethesda, MD
    
31. University of California,San Francisco
    
32. University of Iowa,Iowa City
    
33. The University of Texas Health Science Center at San Antonio
    
34. North Dakota State University, Fargo
    
35. University of North Carolina at Chapel Hill
    
    

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Spotlight on China Nat Med 12(3)

Nat Med 12(3) Mar 2006 published a series of news features about Chinese scholars.

The government plans to increase its annual investment in research and development to 900 billion yuan (US$112 billion) by 2020, a massive increase over the current numbers

Hongyuan Huang, Chaoyang Hospital, Beijing
He collect nasal cells, potentially neural stem cells, from aborted fetuses and injects them into people's spines. He clained his treament could be used for spinal cord injuries or diseases such as amyotrophic lateral sclerosis, Parkinson disease and multiple sclerosis. Despite the life quality improvement described by individual patients, the effects of his treamtent protocol needs to rule out placebo effect. Studies including good control groups are desired.
See also Nat news report.

Yongzhang Luo, Tsinghua University, Beijing
PhD from UC, Berkeley in 1993, Postdoc at harvard and standford from 1994-1998. He's been actively published on JBC, Biochemistry since his return in 1999. He is working on affordable medications for Chinese. Did I say drug discovery?
See more on his webiste at Tsinghua Univ.
See more on Nature news.

Hongkai Deng, Peking University, Beijing
PhD at UCLA, and postdoc at NYU. He won $1.9 million for a proposal to use stem cells to create mouse models for testing HIV and hepatitis C vaccines. Another project is to differenitate embryonic stem cell into insulin-secreting cell--Doug Melton has a new competitor in China. He also coauthored on the Chinese SARS paper on Nat 2006

Unfortunately, the Nat Med missed a star scholar in China, Xuetao Cao. Cao is a newly elected member of Chinese Academy of Engineering, and a professor of immunology at the Second Military Medical University, Shanghai and Zhejiang University at Hangzhou.

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Nat Neurosci 9(3) mar 2006

Full content of Nat Neurosci 9(3)

Ramirez-Castillejo C, F Sanchez-Sanchez, C Andreu-Agullo, SR Ferron, JD Aroca-Aguilar, P Sanchez, H Mira, J Escribano, I Farinas. (2006) Pigment epithelium-derived factor is a niche signal for neural stem cell renewal. Nat Neurosci 9 (3): 331-339
Isabel Fariñas group reported Pigment epithelium–derived factor (PEDF) was secreted by components of the murine SVZ, and could promote self-renewal of neural stem cells(NSC) both in vivo and in vitro. First, they show PEDF presents in ependymal and endothelial cells, but not NSC, in adults. In vitro neurosphere formation data suggest PEDF promotes self-renewal of NSC (formation frequency of neurospheres), but not proliferation (Size of neurospheres). C-ter fragment of PEDF was then found to block effects of full-length PEDF on neurosphere formation. They demonstrate PEDF regulates NSC self-renewal in vivo by infusing PEDF and its antagonist, c-ter PEDF.
I like pharmacological evidence, that provides direct potential of clinical use.
A piece of beautiful work!

Pumiglia K, S Temple. (2006) PEDF: bridging neurovascular interactions in the stem cell niche. Nat Neurosci 9 (3): 299-300
See also commentary of Kevin Pumiglia and Sally Temple

Le Bras B, M-J Barallobre, J Homman-Ludiye, A Ny, S Wyns, T Tammela, P Haiko, MJ Karkkainen, L Yuan, M-P Muriel, E Chatzopoulou, C Breant, B Zalc, P Carmeliet, K Alitalo, A Eichmann, J-L Thomas. (2006) VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brain. Nat Neurosci 9 (3): 340-348
By using VEGF-C knockdown models of xenopus and mouse, Jean-Léon Thomas group demonstrates VEGF-C is required for neural development and induces proliferation of neural progenitor cells, especially VEGFR3+ ones. Briefly, VEGF-C and its receptor were first found present in the embryonic mouse brain. In vitro data suggest VEGF-C induces proliferation of neural progenitor cells derived from optic nerve, especially VEGFR3+ neural progenitor cells, while transgenic mouse lack of VEGF-C has significantly reduced oligodendrocyte precursor cells in optic nerve.

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Nat Cell biol 8(3)

Nat Cell biol 8(3) Mar 2006

Kaji K, IM Caballero, R MacLeod, J Nichols, VA Wilson, B Hendrich. (2006) The NuRD component Mbd3 is required for pluripotency of embryonic stem cells. 8 (3): 285-292
Brian Hendrich group found another gene that regulates pluripotency of Embryonic Stem Cells(ESC), which is Mbd3-a component of the nucleosome remodelling and histone deacetylation (NuRD) complex. Mbd3-deficient ESC could grow in the absence of LIF, and differentiate in embryonic bodies or chimeric embryos with loss of terminal differentiation commitment.

Sirbu IO, G Duester. (2006) Retinoic-acid signalling in node ectoderm and posterior neural plate directs left-right patterning of somitic mesoderm. 8 (3): 271-277
Ioan Ovidiu Sirbu & Gregg Duester demonstrate that retinoic-acid signalling is uniform across the left–right axis and occurs in node ectoderm but not node mesoderm. Retinoic acid rescue data show retinoic-acid signaling targets on node ectoderm and posterior neural plate during somitogenesis, but not presomitic mesoderm.

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Genes & Dev 20(5)

Genes & Dev 20(5) Mar 1, 2006

Covello KL, J Kehler, H Yu, JD Gordan, AM Arsham, C-J Hu, PA Labosky, MC Simon, B Keith. (2006) HIF-2{alpha} regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth 10.1101/gad.1399906. Genes Dev. 20 (5): 557-570
M. Celeste Simon Group reports HIF-2 alpha, but not HIF1, induces Oct-4 expression and impaired embryonic development. It was also found that HIF2 alpha induced tumorigenesis may attribute to dis-regulation of stem cell function through activation of Oct-4.

Gocheva V, W Zeng, D Ke, D Klimstra, T Reinheckel, C Peters, D Hanahan, JA Joyce. (2006) Distinct roles for cysteine cathepsin genes in multistage tumorigenesis 10.1101/gad.1407406. Genes Dev. 20 (5): 543-556

Hallstrom TC, JR Nevins. (2006) Jab1 is a specificity factor for E2F1-induced apoptosis 10.1101/gad.1345006. Genes Dev. 20 (5): 613-623
By using a yeast two-hybrid screen, Joseph R. Nevins group identified Jab1 as a protein that binds the E2F1 marked box and flanking regions. Further work shows Jab1 synergizes with E2F1 to induce apoptosis, but not to promote cell cycle entry.

Valencia-Sanchez MA, J Liu, GJ Hannon, R Parker. (2006) Control of translation and mRNA degradation by miRNAs and siRNAs
10.1101/gad.1399806. Genes Dev. 20 (5): 515-524
Good Review for mRNA regulation

Wu X, F Quondamatteo, T Lefever, A Czuchra, H Meyer, A Chrostek, R Paus, L Langbein, C Brakebusch. (2006) Cdc42 controls progenitor cell differentiation and beta-catenin turnover in skin
10.1101/gad.361406. Genes Dev. 20 (5): 571-585
Cord Brakebusch group found absence of small GTPase Cdc42 increased degradation of beta-catenin through decreased phosphorylation of GSK3 at Ser 9 and increased phosphorylation of axin, and involved in differentiation of hair follicle progenitor cells in vivo.

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