Odds of stem cell transplant restoring fertility are as random as a coin toss — until now

The chances of restoring fertility through sperm stem cell transplant are as random as a coin toss. But a team of scientists developed a new strategy that serves as a ‚weighted coin‘ that can favorably rig the odds to achieve outcomes where fertility is successfully restored.

Quelle: Sciencedaily

Stem cell drugs surprise researchers: Could lead to better drugs in the future

Chemotherapy destroys stem cells, which then cannot develop into immune cells and become part of the body’s defenses. There are drugs that can remedy this, but previously we did not know exactly how these drugs worked. Now, a new study details their function providing new knowledge that may improve stem cell transplantation and lead to better drug design in the future.

Quelle: Sciencedaily

Bauchspeicheldrüsen-Tumore aus dem Labor: Organoide helfen, die Krebsentstehung zu verstehen

Für die Krebsforschung haben Ulmer Wissenschaftlerinnen und Wissenschaftler Bauchspeicheldrüsen-Organoide im Labor gezüchtet. Anhand dieser Modelle aus Stammzellen wollen die Forschenden die Entstehung von Bauchspeicheldrüsenkrebs nachvollziehen. Dadurch erhoffen sie sich neue, patientenspezifische Behandlungsansätze. Zudem könnten diese „duktalen Pankreas-Organoide“ dabei helfen, Tierversuche in der Krebsforschung zu reduzieren. Die aktuelle, in Kooperation mit dem Helmholtz Zentrum in München entstandene Publikation wurde im Journal „Cell Stem Cell“ veröffentlicht.

Quelle: IDW Informationsdienst Wissenschaft

Alzheimer-Modellierung zeigt überraschende Ergebnisse

Der Innsbrucker Molekularbiologe Jerome Mertens und sein Team modellierten erstmals auch die sporadische, nur im Alter auftretende Form von Alzheimer basierend auf Hautzellen von Patient*innen. Die in Cell Stem Cell veröffentlichten Ergebnisse belegen eine Altersabhängigkeit dieser Form der Krankheit und zeigen, dass Alzheimer-Nervenzellen und Krebszellen einiges gemeinsam haben.

Quelle: IDW Informationsdienst Wissenschaft

DKMS launches online platform for healthcare professionals

DKMS invites medical and healthcare professionals working in hematopoietic stem cell transplantation to visit the newly developed DKMS platform at www.professional.dkms.org. This website gives an overview of the work of all our specialist departments and offers comprehensive insights into the non-profit organization’s scientific studies and publications. Furthermore, it provides access to DKMS’ services, resources, grants and support programs. The site features a modern and streamlined design and makes it easy to access essential information.

Quelle: IDW Informationsdienst Wissenschaft

Wie Viren das wachsende Gehirn schädigen

Ein Forscherïnnenteam am IMBA – Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften – erforscht an sogenannten Organoiden, wie manche Viren schwere Fehlbildungen im menschlichen Gehirn auslösen können, mit dem Ziel neue Therapieansätze gegen Infektionen und deren Folgen zu entwickeln. Das berichtet das Team rund um Jürgen Knoblich aktuell im Fachmagazin Cell Stem Cell.

Quelle: IDW Informationsdienst Wissenschaft

Reactivating Aging Stem Cells in the Brain

As people get older, their neural stem cells lose the ability to proliferate and produce new neurons, leading to a decline in memory function. Researchers at the University of Zurich have now discovered a mechanism linked to stem cell aging – and how the production of neurons can be reactivated.

Quelle: IDW Informationsdienst Wissenschaft

Uncovering basic mechanisms of intestinal stem cell self-renewal and differentiation

The gut plays a central role in the regulation of the body’s metabolism and its dysfunction is associated with a variety of diseases, such as obesity, diabetes, colitis and colorectal cancer that affect millions of people worldwide. Targeting endocrine dysfunction by stimulating the formation of specific enteroendocrine cells from intestinal stem cells could be a promising regenerative approach for diabetes therapy. For this, a detailed understanding of the intestinal stem cell lineage and the signals regulating the recruitment of intestinal cell types is critical.

Quelle: Sciencedaily

Reducing treatment-related complication for blood cancer patients

Researchers published promising findings on preventing a common complication to lifesaving blood stem cell transplantation in leukemia.

Quelle: Sciencedaily

Variation in cancer risk among tissues can be explained by the number of stem cell divisions

Tomasetti and Vogelstein show that the lifetime risk of cancers of many different types is strongly correlated with the total number of divisions of the normal self-renewing cells maintaining that tissue’s homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to bad luck, that is, random mutations arising during DNA replication in normal, noncancerous stem cells.

Tomasetti C, Vogelstein B (2015): Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 2 January 2015: Vol. 347 no. 6217 pp. 78-81 DOI: 10.1126/science.1260825

Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci

3D-SIM-based DAPI intensity classification in the Barr body versus the entire nucleus of C2C12 cells. (A) Mid z-section of a DAPI-stained nucleus. The area below the dashed line illustrates the resolution level obtained by wide-field deconvolution microscopy, for comparison. Inset magnifications show the non-uniformly compacted structure of the Barr body resolvable with 3D-SIM (1) and an arbitrary autosomal region with CDCs (2). Scale bars: 5 μm, insets 1 μm. (B) X chromosome-specific painting (green) of Xi (left) and Xa territories (right) of the same nucleus in different z-sections. Note the high convergence between the painted Xi and the DAPI visualized Barr body (arrowheads). Scale bars: 2 μm, insets 1 μm. (C) 3D DAPI intensity classification exemplified for the nucleus shown in (A). Seven DAPI intensity classes displayed in false-color code ranging from class 1 (blue) representing pixels close to background intensity, largely representing the IC, up to class 7 (white) representing pixels with highest density, mainly associated with chromocenters. Framed areas of the Barr body (inset 1) and a representative autosomal region (inset 2) are shown on the right at resolution levels of 3D-SIM, deconvolution and conventional wide-field microscopy. The Xi territory pervaded by lower DAPI intensities becomes evident only at 3D-SIM resolution, whereas both wide-field and deconvolution microscopy imply a concentric increase of density in the Barr body. In the autosomal region, chromatin assigned to classes 2 to 3 lines compacted CDCs, represented by classes 4 to 6. (D) Left: average DAPI intensity classification profiles with standard deviations evaluated for entire nuclear volumes or the Barr body region only (dark grey bars). Right: over/underrepresentation of the average DAPI intensity class fraction sizes in the Barr body versus entire nuclear volumes (n = 12). Distribution differences on classes between Xi and entire nucleus P <0.001. 3D-SIM, three-dimensional structured illumination microscopy; CDC, chromatin domain cluster; DAPI, 4',6-diamidino-2-phenylindole; FISH, fluorescence in situ hybridization; IC, interchromatin compartment; Xa, active X chromosome; Xi, inactive X chromosome. Smeets et al. Epigenetics & Chromatin 2014 7:8   doi:10.1186/1756-8935-7-8
3D-SIM-based DAPI intensity classification in the Barr body versus the entire nucleus of C2C12 cells. (A) Mid z-section of a DAPI-stained nucleus. The area below the dashed line illustrates the resolution level obtained by wide-field deconvolution microscopy, for comparison. Inset magnifications show the non-uniformly compacted structure of the Barr body resolvable with 3D-SIM (1) and an arbitrary autosomal region with CDCs (2). Scale bars: 5 μm, insets 1 μm. (B) X chromosome-specific painting (green) of Xi (left) and Xa territories (right) of the same nucleus in different z-sections. Note the high convergence between the painted Xi and the DAPI visualized Barr body (arrowheads). Scale bars: 2 μm, insets 1 μm. (C) 3D DAPI intensity classification exemplified for the nucleus shown in (A). Seven DAPI intensity classes displayed in false-color code ranging from class 1 (blue) representing pixels close to background intensity, largely representing the IC, up to class 7 (white) representing pixels with highest density, mainly associated with chromocenters. Framed areas of the Barr body (inset 1) and a representative autosomal region (inset 2) are shown on the right at resolution levels of 3D-SIM, deconvolution and conventional wide-field microscopy. The Xi territory pervaded by lower DAPI intensities becomes evident only at 3D-SIM resolution, whereas both wide-field and deconvolution microscopy imply a concentric increase of density in the Barr body. In the autosomal region, chromatin assigned to classes 2 to 3 lines compacted CDCs, represented by classes 4 to 6. (D) Left: average DAPI intensity classification profiles with standard deviations evaluated for entire nuclear volumes or the Barr body region only (dark grey bars). Right: over/underrepresentation of the average DAPI intensity class fraction sizes in the Barr body versus entire nuclear volumes (n = 12). Distribution differences on classes between Xi and entire nucleus P Smeets et al. Epigenetics & Chromatin 2014 7:8 doi:10.1186/1756-8935-7-8

Daniel Smeets, Yolanda Markaki, Volker J Schmid, Felix Kraus, Anna Tattermusch, Andrea Cerase, Michael Sterr, Susanne Fiedler, Justin Demmerle, Jens Popken, Heinrich Leonhardt, Neil Brockdorff, Thomas Cremer1, Lothar Schermelleh and Marion Cremer

Abstract

Background

A Xist RNA decorated Barr body is the structural hallmark of the compacted inactive X territory in female mammals. Using super-resolution three-dimensional structured illumination microscopy (3D-SIM) and quantitative image analysis, we compared its ultrastructure with active chromosome territories (CTs) in human and mouse somatic cells, and explored the spatio-temporal process of Barr body formation at onset of inactivation in early differentiating mouse embryonic stem cells (ESCs).

Results

We demonstrate that all CTs are composed of structurally linked chromatin domain clusters (CDCs). In active CTs the periphery of CDCs harbors low-density chromatin enriched with transcriptionally competent markers, called the perichromatin region (PR). The PR borders on a contiguous channel system, the interchromatin compartment (IC), which starts at nuclear pores and pervades CTs. We propose that the PR and macromolecular complexes in IC channels together form the transcriptionally permissive active nuclear compartment (ANC). The Barr body differs from active CTs by a partially collapsed ANC with CDCs coming significantly closer together, although a rudimentary IC channel system connected to nuclear pores is maintained. Distinct Xist RNA foci, closely adjacent to the nuclear matrix scaffold attachment factor-A (SAF-A) localize throughout Xi along the rudimentary ANC. In early differentiating ESCs initial Xist RNA spreading precedes Barr body formation, which occurs concurrent with the subsequent exclusion of RNA polymerase II (RNAP II). Induction of a transgenic autosomal Xist RNA in a male ESC triggers the formation of an ‘autosomal Barr body’ with less compacted chromatin and incomplete RNAP II exclusion.

Conclusions

3D-SIM provides experimental evidence for profound differences between the functional architecture of transcriptionally active CTs and the Barr body. Basic structural features of CT organization such as CDCs and IC channels are however still recognized, arguing against a uniform compaction of the Barr body at the nucleosome level. The localization of distinct Xist RNA foci at boundaries of the rudimentary ANC may be considered as snap-shots of a dynamic interaction with silenced genes. Enrichment of SAF-A within Xi territories and its close spatial association with Xist RNA suggests their cooperative function for structural organization of Xi.

Continue reading „Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci“