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Kurtz, A.

Publications and source records attributed to Kurtz, A..

6 recordsLinked to original sources

LINC01503-MP is a Mitochondrial Microprotein That Promotes Cell Proliferation and Oxidative Metabolism.

Long non-coding RNAs (lncRNAs) are well-established as key regulators of gene expression. However, emerging evidence reveals that some lncRNAs can also encode functional microproteins. In this study, we report the identification of an evolutionarily young microprotein encoded by LINC01503, expressed across several human tissues. This microprotein, designated as LINC01503-MP, localises to the mitochondria and exerts a proliferative effect on HCT116 colorectal cancer (CRC) cells. Functional studies reveal that LINC01503-MP regulates mitochondrial oxygen consumption rate, linking its activity to enhanced metabolic functions and cell proliferation. Interactome analyses identified multiple mitochondrial metabolism-related proteins as potential interaction partners. Our findings show that LINC01503-MP plays a role in the proliferative phenotype associated with LINC01503 upregulation in CRC, suggesting the functional significance of evolutionarily young, lncRNA-derived microproteins in cancer progression.

molecular biology↗

Extensive monolayer formation depends on a subpopulation of transplanted human iPSC-derived RPE cells

Loss of the retinal pigment epithelium (RPE) in the eye leads to photoreceptor dysfunction and death causing eventually vision loss. Cell replacement strategies using RPE cells derived in vitro from pluripotent stem cells (PSCs) are currently evaluated as a potential therapeutic strategy. Generation of polarized monolayers represents an essential prerequisite for proper RPE function, however, monolayer formation following transplantation of RPE cell suspensions has not been systematically assessed. Using the sodium iodate mouse model of acute RPE depletion, significant increase in monolayer formation capacity of passage (P) 1 vs. P2 human iPSC-derived RPE cells was observed three weeks after transplantation. Transplant-derived monolayers showed characteristic apicobasal polarity, RPE marker expression, phagocytosis function, and preservation of the host outer nuclear layer. The cell surface marker panel CD54+/PSA-NCAM- was identified to enrich for an RPE subpopulation with high potential for monolayer formation following transplantation. Results underline the importance of defining and isolating competent cell subpopulations for successful RPE transplantation.

neuroscience↗

Australian researchers' perceptions and experiences with stem cell registration.

The recently issued ISSCR standards in stem cell research recommend registration of human pluripotent stem cell lines (hPSCs). Registration is an important part of establishing stem cell provenance and connecting cell lines to data derived on those lines. In this study, we sought to understand common barriers to registration, by conducting interviews with forty-eight Australian stem cell stakeholders, including researchers, clinicians, and industry professionals. Australian stem cell researchers do not routinely register their lines, and of those Australian lines captured by an international registry, only a third have completed the registration process. Most registered Australian cell lines miss information about their ethical provenance or key pluripotency characteristics. Incomplete registration is poorly aligned with the goals of open science that registries are founded on, and users themselves expressed concerns about the quality of the partial information provided to the resource. Registration was considered a publication hurdle, and this impacted on user perceptions of usefulness of registration, and lowered the likelihood that they would engage with registries to find resources. Although the Australian community represents a small fraction of registry users, the results of this study may suggest ways for journals, registries, and the stem cell community to improve registration compliance. HighlightsResearchers who perceive registration as a publication hurdle are unlikely to complete the registration process. Incomplete registration promotes misunderstandings about the goals and quality of a registry. Full registration of pluripotent stem cell lines is an important step in verifying cell line provenance. Greater public awareness of registration, combined with requirements for full registration by journals will support the community adopt ISSCR recommendations to register lines.

scientific communication and education↗

Human iPSC-derived renal cells change their immunogenic properties during maturation: Implications for regenerative therapies

Therapeutic success of human induced pluripotent stem cell (hiPSC)-based therapies critically depends on immunological compatibility of the hiPSC-derived transplant. As grafted hiPSC-derived cells are often immature, we hypothesized that their immunologic properties may change due to post-grafting maturation. Subsequently, this will affect their interaction with the host immune system and may compromise graft tolerance. In the present study allogeneic and autologous cellular immunity of primary cells, therof reprogrammed hiPSC, hiPSC-derived progenitor and terminally differentiated cells was investigated in vitro by using renal cells as a model system. In contrast to allogeneic primary cells, hiPSC-derived early renal progenitors and mature renal epithelial cells were both tolerated not only by autologous but also by allogeneic T cells. These immune-privileged properties resulted from active immune-modulation and low immune visibility, which declined during the process of cell maturation. However, autologous and allogeneic natural killer (NK) cell responses were not suppressed by hiPSC-derived renal cells and efficiently changed NK cell activation status. These findings clearly show a dynamic stage-specific dependency of autologous and allogeneic T- and NK cell responses to the hiPSC-derived renal cell lineage with consequences for effective cell therapies. The study suggests that hiPSC-derived early progenitors may provide advantageous immune suppressive properties when applied in cell therapy. The data furthermore indicate a need to suppress NK cell activation in allogeneic as well as autologous settings.

cell biology↗

Integrated Collection of Stem Cell Bank data, a data portal for standardized stem cell information

The last decade has witnessed an extremely rapid increase in the number of newly established stem cell lines. However, due to the lack of a standardized format, data exchange among stem cell line resources has been challenging, and no system can search all stem cell lines across resources worldwide. To solve this problem, we have developed Integrated Collection of Stem Cell Bank data (ICSCB) (http://icscb.stemcellinformatics.org/), the largest database search portal for stem cell line information, based on the standardized data items and terms of the MIACARM framework. Currently, ICSCB can retrieve >16,000 cell lines from four major data resources in Europe, Japan, and the United States. ICSCB is automatically updated to provide the latest cell line information, and its integrative search helps users collect cell line information for over 1,000 diseases including many rare diseases worldwide, which has been a formidable task, thereby distinguishing itself from other database search portals.

bioinformatics↗

Evaluating Cell Identity from Transcription Profiles

Induced pluripotent stem cells (iPS) and direct lineage programming offer promising autologous and patient-specific sources of cells for personalized drug-testing and cell-based therapy. Before these engineered cells can be widely used, it is important to evaluate how well the engineered cell types resemble their intended target cell types. We have developed a method to generate CellScore, a cell identity score that can be used to evaluate the success of an engineered cell type in relation to both its initial and desired target cell type, which are used as references. Of 20 cell transitions tested, the most successful transitions were the iPS cells (CellScore > 0.9), while other transitions (e.g. induced hepatocytes or motor neurons) indicated incomplete transitions (CellScore < 0.5). In principle, the method can be applied to any engineered cell undergoing a cell transition, where transcription profiles are available for the reference cell types and the engineered cell type.\n\nHighlightsO_LIA curated standard dataset of transcription profiles from normal cell types was created.\nC_LIO_LICellScore evaluates the cell identity of engineered cell types, using the curated dataset.\nC_LIO_LICellScore considers the initial and desired target cell type.\nC_LIO_LICellScore identifies the most successfully engineered clones for further functional testing.\nC_LI

bioinformatics↗