Beyond Stem Cells: Self-Renewal of Differentiated Macrophages

Here below a structured abstract about stem cells from the 22 November issue of the journal Science. The authors of this review article are: Michael H. Sieweke and Judith E. Allen.

Background

Many mature cells of the body are continuously replaced, particularly in tissues that are most exposed to the environment such as cells of the immune system. The need for new cells is driven by cellular turnover during normal tissue homeostasis and is further increased upon infection. Because differentiated cells typically withdraw from the cell cycle, replacement of mature cells is generally thought to depend on differentiation of self-renewing, tissue-specific stem cells. Until recently, tissue macrophages were thought to follow such a pathway, developing from hematopoietic stem cells via bone marrow–progenitor and blood monocyte intermediates. But this view has changed of late with several observations indicating that macrophages can self-renew by local proliferation of mature differentiated cells.

 Macrophage origin and self-renewal. In the classical view, macrophages develop from self-renewing hematopoietic stem cells (HSC) in the bone marrow (BM) via blood monocyte intermediates. However, new data show that some adult tissue macrophage populations develop from embryonic progenitors independent of HSCs and can self-renew. Local proliferation can assure homeostatic maintenance (dotted arrows) and dramatically increase cell number (solid arrows) upon challenge.  From https://www.sciencemag.org/content/342/6161/1242974.abstract

Advances

Recent studies have demonstrated that in macrophages, differentiation and cell cycle withdrawal can be uncoupled by the inactivation of specific transcription factors. These cells can then be expanded indefinitely as functionally differentiated macrophages without tumorigenic transformation. At the same time, it became clear that mature macrophages could also expand massively in vivo in response to infections by local proliferation, independently of input from adult hematopoietic stem cells. Furthermore, several populations of tissue macrophages were found to be derived from embryonic progenitors, and macrophages can be self-maintained in adult tissues by local proliferation. Together, these recent data suggest that macrophages are mature differentiated cells that may be endowed with self-renewal capacity akin to that of stem cells.

Outlook

These findings challenge the classical view of tissue maintenance by adult tissue-specific stem cells and indicate that stem cell–like self-renewal mechanisms may be activated in mature differentiated cells. It will be important to determine whether the engaged pathways resemble those active in stem cells and whether they might be activated in other cell types as well. Furthermore, we need to understand how such self-renewal capacity differs from uncontrolled proliferation induced by oncogenic transformation. A first step will be to explore how macrophage proliferation is regulated in vivo: How do macrophages adapt their cell numbers to diverse tissue requirements, from near quiescence during homeostasis to massive expansion under challenge? Macrophages are present in nearly every tissue and serve important functions in immunity, cancer, metabolism, and tissue repair. The role of local macrophage proliferation in these processes has remained largely unexplored. It will be important to investigate how the consequences of macrophage accumulation by local proliferation differ from those of monocyte-derived macrophage recruitment under inflammatory conditions. The control of macrophage numbers independent of inflammatory signals may provide new opportunities for therapeutic intervention in many of these areas.

Macrophage Makeover

Macrophages are important immune cells that function in tissue repair during homeostasis and in the innate immune response. Inflammation, which can be triggered by infection, is accompanied by a massive expansion of macrophages in affected tissues. The major source of this increase in resident macrophages has been thought to be hematopoietic stem cells in the bone marrow. However, recent results have shown that the mature differentiated macrophages residing in the affected tissues can themselves proliferate to boost cell numbers. Sieweke and Allen (10.1126/science.1242974) review what we know about the origin of macrophages and outline the consequences of local macrophage proliferation for the immune response and tissue homeostasis.

More information about the article: Science 22 November 2013 Vol. 342 no. 6161

Authors and affiliations:Michael H. Sieweke1 2 3 4

Judith E. Allen5

1Centre d’Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. 2Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, Marseille, France. 3Centre National de la Recherche Scientifique (CNRS), UMR7280, Marseille, France. 4Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Strasse 10, 13125 Berlin, Germany. 5Centre for Immunity, Infection and Evolution, and the Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, UK.

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Association of classroom ventilation with reduced illness absence: a prospective study in California elementary schools

St. John's School, Perth, Scotland from the upper playground (c)Btoner1971947

The last issue of Indoor Air reports an interesting article regarding the relationship between air ventilation in classrooms and the probability of students illness. The authors M.J. Mendell, E.A. Eliseeva, M.M. Davies, M. Spears, A. Lobscheid, W. J. Fisk, M.G. Apte from Lawrence Berkeley National Laboratory (California, USA). Here below the abstract of the article.

Limited evidence associates inadequate classroom ventilation rates (VRs) with increased illness absence (IA). We investigated relationships between VRs and IA in California elementary schools over two school years in 162 3rd–5th-grade classrooms in 28 schools in three school districts: South Coast (SC), Bay Area (BA), and Central Valley (CV). We estimated relationships between daily IA and VR (estimated from two year daily real-time carbon dioxide in each classroom) in zero-inflated negative binomial models. We also compared IA benefits and energy costs of increased VRs. All school districts had median VRs below the 7.1 l/s-person California standard. For each additional 1 l/s-person of VR, IA was reduced significantly (p<0.05) in models for combined districts (−1.6%) and for SC (−1.2%), and nonsignificantly for districts providing less data: BA (−1.5%) and CV (−1.0%). Assuming associations were causal and generalizable, increasing classroom VRs from the California average (4 l/s-person) to the State standard would decrease IA by 3.4%, increase attendance-linked funding to schools by $33 million annually, and increase costs by only $4 million. Further increasing VRs would provide additional benefits. These findings, while requiring confirmation, suggest that increasing classroom VRs above the State standard would substantially decrease illness absence and produce economic benefits.

More information about the article: Indoor Air Volume 23, Issue 6, pages 515–528, December 2013

Authors and affiliations:

Indoor Environment Group, Environmental Energy Technologies Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA

M.J. Mendell, E.A. Eliseeva, M.M. Davies, M. Spears, A. Lobscheid, W. J. Fisk, M.G. Apte

Potential water saving through changes in European diets

An irrigation canal south of Culver.(c) Gary Halvorson, Oregon State Archives

In the last issue of Environmental International D. Vanham, A.Y. Hoekstra, G. Bidoglio have published an article concerning the consumption of water and European diets. Here the abstract.

This study quantifies the water footprint of consumption (WFcons) regarding agricultural products for three diets – the current diet (REF), a healthy diet (HEALTHY) and a vegetarian diet (VEG) – for the four EU zones WEST, NORTH, SOUTH and EAST. The WFcons related to the consumption of agricultural products (4265 l per capita per day or lcd) accounts for 89% of the EU's total WFcons (4815 lcd). The effect of diet has therefore an essential impact on the total WFcons. The current zonal WFcons regarding agricultural products is: 5875 lcd (SOUTH), 4053 lcd (EAST), 3761 lcd (WEST) and 3197 lcd (NORTH). These differences are the result of different consumption behaviours as well as different agricultural production methods and conditions. From the perspective of a healthy diet based on regional dietary guidelines, the intake of several product groups (sugar, crop oils, animal fats and meat) should be decreased and increased for others (vegetables, fruit). The WFcons regarding agricultural products for the alternative diets are the following: HEALTHY 4110 lcd (− 30%) and VEG 3476 lcd (− 41%) for SOUTH; HEALTHY 3606 lcd (− 11%) and VEG 2956 lcd (− 27%) for EAST; HEALTHY 2766 lcd (− 26%) and VEG 2208 lcd (− 41%) for WEST; HEALTHY 3091 lcd (− 3%) and VEG 2166 lcd (− 32%) for NORTH. Both the healthy and vegetarian diets thus result – consistent for all zones – in substantial WFcons reductions. The largest reduction takes place for the vegetarian diet. Indeed, a lot of water can be saved by EU citizens by a change in their diet.

Follow this link for more information about this article: Environment International  Volume 61, November 2013, Pages 45–56

Affiliations:

European Commission, Joint Research Centre, Institute for Environment and Sustainability, Via E. Fermi 2749, 21027 Ispra, VA, Italy

D. Vanham, G. Bidoglio

Department of Water Engineering and Management, University of Twente, Enschede, The Netherlands
A.Y. Hoekstra

Influential parameters on particle concentration and size distribution in the mainstream of e-cigarettes

F.C. Fuoco, G. Buonanno, L. Stabile and P. Vigo from the University of Cassino (Italy), in this article report an interesting study about the aerosol produced by the electronic cigarettes (e-cigarettes). Here below the abstract.

Electronic cigarette-generated mainstream aerosols were characterized in terms of particle number concentrations and size distributions through a Condensation Particle Counter and a Fast Mobility Particle Sizer spectrometer, respectively. A thermodilution system was also used to properly sample and dilute the mainstream aerosol.

Different types of electronic cigarettes, liquid flavors, liquid nicotine contents, as well as different puffing times were tested. Conventional tobacco cigarettes were also investigated.

The total particle number concentration peak (for 2-s puff), averaged across the different electronic cigarette types and liquids, was measured equal to 4.39 ± 0.42 × 10⁹ part. cm⁻³, then comparable to the conventional cigarette one (3.14 ± 0.61 × 10⁹ part. cm⁻³). Puffing times and nicotine contents were found to influence the particle concentration, whereas no significant differences were recognized in terms of flavors and types of cigarettes used.

Particle number distribution modes of the electronic cigarette-generated aerosol were in the 120–165 nm range, then similar to the conventional cigarette one.

Follow the link below to go to article website:

Environmental Pollution Volume 184, January 2014, Pages 523–529

Affiliations: 

Department of Civil and Mechanical Engineering, University of Cassino and Southern Lazio, via Di Biasio 43, Cassino 03043, Italy

F.C. Fuoco, G. Buonanno, L. Stabile and P. Vigo

Queensland University of Technology, Brisbane, Australia

G. Buonanno

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Mutational landscape and significance across 12 major cancer types

(c) Zephyris at the English language Wikipedia

This article has been written by a team of the Washington University in St Louis (USA) and Brown University (Providence, USA).

The authors are: Cyriac Kandoth, Michael D. McLellan, Fabio Vandin, Kai Ye, Beifang Niu, Charles Lu, Mingchao Xie, Qunyuan Zhang, Joshua F. McMichael, Matthew A. Wyczalkowski, Mark D. M. Leiserson, Christopher A. Miller, John S. Welch, Matthew J. Walter, Michael C. Wendl, Timothy J. Ley, Richard K. Wilson, Benjamin J. Raphael & Li Ding.

The Cancer Genome Atlas (TCGA) has used the latest sequencing and analysis methods to identify somatic variants across thousands of tumours. Here we present data and analytical results for point mutations and small insertions/deletions from 3,281 tumours across 12 tumour types as part of the TCGA Pan-Cancer effort. We illustrate the distributions of mutation frequencies, types and contexts across tumour types, and establish their links to tissues of origin, environmental/carcinogen influences, and DNA repair defects. Using the integrated data sets, we identified 127 significantly mutated genes from well-known (for example, mitogen-activated protein kinase, phosphatidylinositol-3-OH kinase, Wnt/β-catenin and receptor tyrosine kinase signalling pathways, and cell cycle control) and emerging (for example, histone, histone modification, splicing, metabolism and proteolysis) cellular processes in cancer. The average number of mutations in these significantly mutated genes varies across tumour types; most tumours have two to six, indicating that the number of driver mutations required during oncogenesis is relatively small. Mutations in transcriptional factors/regulators show tissue specificity, whereas histone modifiers are often mutated across several cancer types. Clinical association analysis identifies genes having a significant effect on survival, and investigations of mutations with respect to clonal/subclonal architecture delineate their temporal orders during tumorigenesis. Taken together, these results lay the groundwork for developing new diagnostics and individualizing cancer treatment.

This is an open access article; you can read the full text following the link
Nature  502, 333–339 (17 October 2013)

 

Affiliations:

The Genome Institute, Washington University in St Louis, Missouri 63108, USA

Cyriac Kandoth, Michael D. McLellan, Kai Ye, Beifang Niu, Charles Lu, Mingchao Xie, Qunyuan Zhang, Joshua F. McMichael, Matthew A. Wyczalkowski, Christopher A. Miller, Michael C. Wendl, Timothy J. Ley, Richard K. Wilson & Li Ding

Department of Computer Science, Brown University, Providence, Rhode Island 02912, USA

Fabio Vandin, Mark D. M. Leiserson & Benjamin J. Raphael

Department of Genetics, Washington University in St Louis, Missouri 63108, USA

Kai Ye, Qunyuan Zhang, Michael C. Wendl, Timothy J. Ley, Richard K. Wilson & Li Ding

Department of Medicine, Washington University in St Louis, Missouri 63108, USA

John S. Welch, Matthew J. Walter, Timothy J. Ley & Li Ding

Siteman Cancer Center, Washington University in St Louis, Missouri 63108, USA

John S. Welch, Matthew J. Walter, Timothy J. Ley, Richard K. Wilson & Li Ding

Department of Mathematics, Washington University in St Louis, Missouri 63108, USA

Michael C. Wend 

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