Breast milk contains stem cells

This is via Leslie's Life Log but it is an interesting finding and from the web site Science Alert for Oceania and has important for understanding human development and the role endogenous retroviruses may play in development (more on this in a future blog).

Breast milk contains stem cells

Monday, 11 February 2008

By Catherine Madden

The Perth scientist who made the world-first discovery that human breast milk contains stem cells is confident that within five years scientists will be harvesting them to research treatment for conditions as far-reaching as spinal injuries, diabetes and Parkinson’s disease.

But what Dr Mark Cregan is excited about right now is the promise that his discovery could be the start of many more exciting revelations about the potency of breast milk.

He believes that it not only meets all the nutritional needs of a growing infant but contains key markers that guide his or her development into adulthood.

“We already know how breast milk provides for the baby’s nutritional needs, but we are only just beginning to understand that it probably performs many other functions,” says Dr Cregan, a molecular biologist at The University of Western Australia.

He says that, in essence, a new mother’s mammary glands take over from the placenta to provide the development guidance to ensure a baby’s genetic destiny is fulfilled.

“It is setting the baby up for the perfect development,” he says. “We already know that babies who are breast fed have an IQ advantage and that there’s a raft of other health benefits. Researchers also believe that the protective effects of being breast fed continue well into adult life.

“The point is that many mothers see milks as identical – formula milk and breast milk look the same so they must be the same. But we know now that they are quite different and a lot of the effects of breast milk versus formula don’t become apparent for decades. Formula companies have focussed on matching breast milk’s nutritional qualities but formula can never provide the developmental guidance.”

It was Dr Cregan’s interest in infant health that led him to investigate the complex cellular components of human milk. “I was looking at this vast complexity of cells and I thought, ‘No one knows anything about them’.”

His hunch was that if breast milk contains all these cells, surely it has their precursors, too?

His team cultured cells from human breast milk and found a population that tested positive for the stem cell marker, nestin. Further analysis showed that a side population of the stem cells were of multiple lineages with the potential to differentiate into multiple cell types. This means the cells could potentially be “reprogrammed” to form many types of human tissue.

He presented his research at the end of January to 200 of the world’s leading experts in the field at the International Conference of the Society for Research on Human Milk and Lactation in Perth.

“We have shown these cells have all the physical characteristics of stem cells. What we will do next is to see if they behave like stem cells,” he says.

If so, they promise to provide researchers with an entirely ethical means of harvesting stem cells for research without the debate that has dogged the harvesting of cells from embryos.

Further research on immune cells, which have also been found in breast milk and have already been shown to survive the baby’s digestive process, could provide a pathway to developing targets to beat certain viruses or bacteria.

Darwin's Suprise: HERVs

The New Yorker has an awesome (yes I come from the 80s) article (here) on current research on endogenous retroviruses. The article gives a good run down of the background that 8% of the genome is made up of these hitchhiking viruses while only 2% of the genome causes anything. Then they go into the experiment where Thierry Heidmann brought one back to life and then mixed it with human cells where it reinserted itself into the genome and published it in the paper entitled "Identification of an Infectious Progenitor for the Multiple-Copy HERV-K Human Endogenous Retroelements". It also talks about how you can build your own virus with a labtop and a PO Box but also why it is great leap forward in our understanding of the genome. You see these viruses are not only viruses but genes and they way they insert themselves into the genome, with the enzyme reverse transcriptase, as important implications for how humans evolved but also for diseases.

One persons junk

This is a great article from Science Daily regarding a study on how ancient retroviruses (called HERVs, this always reminds me of the Burger King Herb commercials from the 1980s) inserted into primate genomes may have important implications for understanding gene regulations, in this case p53 (a tumor suppressor protein). Here are couple of quotes from the article. I like article like these because they open so many different areas of study.

Scientists have long suspected that retroviral elements could play a role in gene regulation. More than 50 years ago, Nobel Laureate Barbara McClintock observed that transposable elements--or "jumping genes"--altered gene expression in maize. In 1971, Roy Britten and Eric Davidson theorized that commonly observed repetitive DNA sequences actually served as codes for gene regulatory networks. The DNA remnants of retroviruses tend to be repetitive sequences and can jump around, when active.

....... "We're starting to uncover the treasure in this junk," said Wang.

Moreover, the team has proposed a new mechanism for evolutionary change. Conventional wisdom says that evolution is driven by small changes--point mutations--to the genetic code. If a change is beneficial, the mutation is passed onto future generations.

Here is a link to the article and the abstract. If you like Science Fiction I also suggest you check out Greg Bear's Darwin's Radio, which is very anthropological in scope.

Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53

Ting Wang^*, Jue Zeng, Craig B. Lowe^*, Robert G. Sellers^*,, Sofie R. Salama^*,, Min Yang, Shawn M. Burgess, Rainer K. Brachmann^,¶,||, and David Haussler*^*,,||

*Center for Biomolecular Science and Engineering, and Howard Hughes Medical Institute, University of California, Santa Cruz, CA 95064; Division of Hematology/Oncology, Departments of Medicine and Biological Chemistry, University of California, Irvine, CA 92697; and Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892

Edited by Eric H. Davidson. California Institute of Technology, Pasadena, CA, and approved September 26, 2007 (received for review April 27, 2007)

Abstract

The evolutionary forces that establish and hone target gene networks of transcription factors are largely unknown. Transposition of retroelements may play a role, but its global importance, beyond a few well described examples for isolated genes, is not clear. We report that LTR class I endogenous retrovirus (ERV) retroelements impact considerably the transcriptional network of human tumor suppressor protein p53. A total of 1,509 of 319,000 human ERV LTR regions have a near-perfect p53 DNA binding site. The LTR10 and MER61 families are particularly enriched for copies with a p53 site. These ERV families are primate-specific and transposed actively near the time when the New World and Old World monkey lineages split. Other mammalian species lack these p53 response elements. Analysis of published genomewide ChIP data for p53 indicates that more than one-third of identified p53 binding sites are accounted for by ERV copies with a p53 site. ChIP and expression studies for individual genes indicate that human ERV p53 sites are likely part of the p53 transcriptional program and direct regulation of p53 target genes. These results demonstrate how retroelements can significantly shape the regulatory network of a transcription factor in a species-specific manner.

Articles of interest

So while I was gone, I didn't really post on any of the issues that were impacting anthropology, the James Watson IQ flap, Neanderthals and skin color, the death of Washoe (which made me very sad), or the fact that the Kansas football is almost 9-0 (a sure sign of hell freezing over). Anyway, now that I'm back in the states here are a few article from PLOS One that caught my eye.

Evidence for Positive Selection in the C-terminal Domain of the Cholesterol Metabolism Gene PCSK9 Based on Phylogenetic Analysis in 14 Primate Species

Keyue Ding, Samantha J. McDonough, Iftikhar J. Kullo

Background
Cholesterol homeostasis is maintained through finely tuned mechanisms regulating intestinal absorption, hepatic biosynthesis and secretion as well as plasma clearance. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted enzyme of the serine protease family that reduces cellular uptake of plasma low-density lipoprotein (LDL) cholesterol by promoting LDL receptor (LDL-R) degradation. Species-specific positive selection has been noted in the LDLR promoter, leading to differential expression of LDLR among primates. Whether PCSK9 experienced significant selective pressure to maintain a functional relationship with its target protein, LDL-R, is unknown.
Methodology/Principal Findings
We compiled the sequences of the coding regions of PCSK9 from 14 primate species in the clade of Hominoids, Old World monkeys and New World monkeys. To detect selective pressure at the protein level, the ratios of nonsynonymous/synonymous substitution rate (dN/dS) under different evolutionary models were calculated across the phylogeny of PCSK9. Maximum likelihood analyses of dN/dS ratios for the aligned coding region sequences among 14 primate species indicated that PCSK9 was subject to a strong functional constraint (i.e., purifying selection). However, positive selection was noted in the functional carboxyl-terminal (C-terminal) domain in many branches across the phylogeny, especially in the lineage leading to the orangutan. Furthermore, at least five positively selected amino acids were detected in this lineage using the branch-site model A. In a sliding-window analysis, several dN/dS peaks in the C-terminal domain in both the human and the orangutan branches were noted.
Conclusions
These results suggest that among primates, differential selective pressure has shaped evolutionary patterns in the functional domains of PCSK9, an important regulator of cholesterol homeostasis.

Demographic Histories of ERV-K in Humans, Chimpanzees and Rhesus Monkeys
Camila M. Romano1, Fernando L. de Melo1, Marco Aurelio

B. Corsini1, Edward C. Holmes2,3, Paolo M. de A. Zanotto1*

We detected 19 complete endogenous retroviruses of the K family in the genome of rhesus monkey (Macaca mulatta; RhERV-K) and 12 full length elements in the genome of the common chimpanzee (Pan troglodytes; CERV-K). These sequences were compared with 55 human HERV-K and 20 CERV-K reported previously, producing a total data set of 106 full-length ERV-K genomes. Overall, 61% of the human elements compared to 21% of the chimpanzee and 47% of rhesus elements had estimated integration times less than 4.5 million years before present (MYBP), with an average integration times of 7.8 MYBP, 13.4 MYBP and 10.3 MYBP for HERV-K, CERV-K and RhERV-K, respectively. By excluding those ERV-K sequences generated by chromosomal duplication, we used 63 of the 106 elements to compare the population dynamics of ERV-K among species. This analysis indicated that both HERV-K and RhERV-K had similar demographic histories, including markedly smaller effective population sizes, compared to CERV-K. We propose that these differing ERV-K dynamics reflect underlying differences in the evolutionary ecology of the host species, such that host ecology and demography represent important determinants of ERV-K dynamics.

Prions and Retroviruses

This is from a couple of weeks ago and I'm just getting back to it. Science Daily had a short news bit about how prions may activate endogenous retroviruses in brain cells.

Prion infection influences murine endogenous retrovirus expression in neuronal cells.
Stengel A, Bach C, Vorberg I, Frank O, Gilch S, Lutzny G, Seifarth W, Erfle V, Maas E, Schätzl H, Leib-Mösch C, Greenwood AD.
Institute of Molecular Virology, GSF National Research Center for Environment and Health, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany.

Prions as causative agents of transmissible spongiform encephalopathies have been well investigated in experimental and modelling work. However, little is known about the molecular pathogenesis of prion-induced encephalopathies, the role of co-factors, and the interaction of prions with cellular components. We investigated the influence of prion infection on expression of murine endogenous retroviruses (ERVs), which compose approximately 10% of the mouse genome. Hypothalamic neuronal cells (GT1) and neuroblastoma cells (N2a) were examined. Both cell lines can be persistently infected with mouse adapted prion strains, i.e., RML. Using a mammalian retrovirus-specific DNA microarray and quantitative PCR methods, we compared the expression profiles of ERVs in prion-infected, uninfected, and anti-prion compound-treated murine neuronal cell lines, including clonal cell populations. The results suggest that prion infection influences ERV expression in neuronal cell lines, that this influence is cell line-specific, ERV-specific, and responsive to anti-prion compound treatment.