Leung Lab Blog

There is an interesting news article “Printing Muscle” from Technology Review about using 3-D printers to print muscle cells so that they may assume a 3-D shape that resembles muscle fiber. The idea sounds interesting, because one can potentially print tissues or even organs that have complicated cellular composition in 3-D for regenerative medicine.

From Discover magazine: “Helpful Mouse Fetuses Naturally Send Stem Cells to Mom to Fix Her Damaged Heart”

The punchline is

When a pregnant mouse has a heart attack, her fetus donates some of its stem cells to help rebuild the damaged heart tissue.

The original article is available here.

Kara RJ, Bolli P, Karakikes I, Matsunaga I, Tripodi J, Tanweer O, Altman P, Shachter NS, Nakano A, Najfeld V, Chaudhry HW. Fetal Cells Traffic to Injured Maternal Myocardium and Undergo Cardiac Differentiation. Circ Res. 2011 Nov 14. [Epub ahead of print] PubMed PMID: 22082491.

Medical Research

*These two articles point out the problems of using animal models for research if the goal is to extract translational values and how mouse model, the gold standard for disease research, can actually be a poor reference standard because of the ways we want to standardize the biological tool for testing.

1. Lynch VJ. Use with caution: developmental systems divergence and potential pitfalls of animal models. Yale J Biol Med. 2009 Jun;82(2):53-66. Review. PubMed PMID: 19562005; PubMed Central PMCID: PMC2701150.
2. Martin B, Ji S, Maudsley S, Mattson MP. “Control” laboratory rodents are metabolically morbid: why it matters. Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6127-33. Epub 2010 Mar 1. PubMed PMID: 20194732; PubMed Central PMCID: PMC2852022.

Genomics

1. Tariq MA, Kim HJ, Jejelowo O, Pourmand N. Whole-transcriptome RNAseq analysis from minute amount of total RNA. Nucleic Acids Res. 2011 Oct 1;39(18):e120. Epub 2011 Jul 6. PubMed PMID: 21737426; PubMed Central PMCID: PMC3185437.
2. Compeau PE, Pevzner PA, Tesler G. How to apply de Bruijn graphs to genome assembly. Nat Biotechnol. 2011 Nov 8;29(11):987-91. doi: 10.1038/nbt.2023. PubMed PMID: 22068540.
3. Ala-Korpela M, Kangas AJ, Inouye M. Genome-wide association studies and systems biology: together at last. Trends Genet. 2011 Oct 20. [Epub ahead of print] PubMed PMID: 22018481.

Regeneration

1. Kroehne V, Freudenreich D, Hans S, Kaslin J, Brand M. Regeneration of the adult zebrafish brain from neurogenic radial glia-type progenitors. Development.  2011 Nov;138(22):4831-41. Epub 2011 Oct 17. PubMed PMID: 22007133.

Disease/Evolution

1. Cusack BP, Arndt PF, Duret L, Roest Crollius H. Preventing dangerous nonsense: selection for robustness to transcriptional error in human genes. PLoS Genet. 2011 Oct;7(10):e1002276. Epub 2011 Oct 13. PubMed PMID: 22022272; PubMed Central PMCID: PMC3192821.
• Commentary: Wilke CO. Transcriptional robustness complements nonsense-mediated decay in humans. PLoS Genet. 2011 Oct;7(10):e1002296. Epub 2011 Oct 13. PubMed PMID:22022274; PubMed Central PMCID: PMC3192817.
2. Shelly T, McInnis D. Road test for genetically modified mosquitoes. Nat Biotechnol. 2011 Nov 8;29(11):984-5. doi: 10.1038/nbt.2025. PubMed PMID: 22068534.

Eye Disease

1. Johnson LV, Forest DL, Banna CD, Radeke CM, Maloney MA, Hu J, Spencer CN, Walker AM, Tsie MS, Bok D, Radeke MJ, Anderson DH. Cell culture model that mimics drusen formation and triggers complement activation associated with age-related macular degeneration. Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18277-82. Epub 2011 Oct 3. PubMed PMID: 21969589.
2. Jiang L, Zhang H, Dizhoor AM, Boye SE, Hauswirth WW, Frederick JM, Baehr W. Long-term RNA interference gene therapy in a dominant retinitis pigmentosa mouse model. Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18476-81. Epub 2011 Oct 31. PubMed PMID: 22042849.

Evolution

1. Liu R, Ochman H. Stepwise formation of the bacterial flagellar system. Proc Natl Acad Sci U S A. 2007 Apr 24;104(17):7116-21. Epub 2007 Apr 16. Erratum in: Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11507. PubMed PMID: 17438286; PubMed Central PMCID: PMC1852327.

Systems biology

1. Navlakha S, Bar-Joseph Z. Algorithms in nature: the convergence of systems biology and computational thinking. Mol Syst Biol. 2011 Nov 8;7:546. doi: 10.1038/msb.2011.78. PubMed PMID: 22068329.
2. Ala-Korpela M, Kangas AJ, Inouye M. Genome-wide association studies and systems biology: together at last. Trends Genet. 2011 Oct 20. [Epub ahead of print] PubMed PMID: 22018481.
3. Cheong R, Rhee A, Wang CJ, Nemenman I, Levchenko A. Information transduction capacity of noisy biochemical signaling networks. Science. 2011 Oct 21;334(6054):354-8. Epub 2011 Sep 15. PubMed PMID: 21921160.

Biotech business

1. Francisco M. Third-quarter biotech job picture. Nat Biotechnol. 2011 Nov 8;29(11):1052. doi: 10.1038/nbt.2037. PubMed PMID: 22068542.

We have briefly touched the subject of stem cell research in the last journal club. The challenge of developing “stem cell” as a useful therapy is three fold:

1. Turning the clock of a differentiated cell back to the very beginning.
2. Guiding the resulting dedifferentiated “stem cells” or any kinds of “stem cells” to develop into the appropriate cell types.
3. Incorporating these new cells into the existing organ system properly.

In one sense, the premise of 1 and 2 is that 3 would happen automatically once you can get the Stem cells. They are not only expected to become the desired cell type, but also are expected to know what to do inside the body. This can be a tall order.

There is actually a lot to learn from basic research to see how mother nature deals with the regeneration problem. Salamander is a great regeneration model. If you cut its limb off, the cells in the wound region will grow back a limb to its entirety.

It has long been thought that these cells that are responsible for the regeneration process are pluripotent, or “stem cell”-like. A very interesting research has proven it is otherwise. The original cells in the limb actually remember their identities, and they will only grow back to their own kind. In other words, muscle cells will become muscle cells, and skin cells will become skin cells.

It looks like that instead of having some very specialized stem cells that switch all the way  back to the beginning, the differentiated cells just go back a few (?) steps and maintain their identities during the process. One wonders how this process is regulated at the network level and what has been lost in us that we do not have this capability anymore. Maybe this talent is still hibernating somewhere in our genome, waiting for us to turn it back on.

References:

Sánchez Alvarado A. A cellular view of regeneration. Nature. 2009 Jul 2;460(7251):39-40. [PubMed][Nature]

Kragl M, Knapp D, Nacu E, Khattak S, Maden M, Epperlein HH, Tanaka EM. Cells keep a memory of their tissue origin during axolotl limb regeneration. Nature. 2009 Jul 2;460(7251):60-5. [PubMed][Nature]