Publications by authors named "Pernille Rainer"

3 Publications

  • Page 1 of 1

Toward a Consensus View of Mammalian Adipocyte Stem and Progenitor Cell Heterogeneity.

Trends Cell Biol 2020 12 23;30(12):937-950. Epub 2020 Oct 23.

Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland; Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland. Electronic address:

White adipose tissue (WAT) is a cellularly heterogeneous endocrine organ that not only serves as an energy reservoir, but also actively participates in metabolic homeostasis. Among the main constituents of adipose tissue are adipocytes, which arise from adipose stem and progenitor cells (ASPCs). While it is well known that these ASPCs reside in the stromal vascular fraction (SVF) of adipose tissue, their molecular heterogeneity and functional diversity is still poorly understood. Driven by the resolving power of single-cell transcriptomics, several recent studies provided new insights into the cellular complexity of ASPCs among different mammalian fat depots. In this review, we present current knowledge on ASPCs, their population structure, hierarchy, fat depot-specific nature, function, and regulatory mechanisms, and discuss not only the similarities, but also the differences between mouse and human ASPC biology.
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http://dx.doi.org/10.1016/j.tcb.2020.09.007DOI Listing
December 2020

The NAD-Booster Nicotinamide Riboside Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance.

Cell Stem Cell 2019 03;24(3):405-418.e7

Service and Central Laboratory of Hematology, Departments of Oncology and of Laboratories, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.

It has been recently shown that increased oxidative phosphorylation, as reflected by increased mitochondrial activity, together with impairment of the mitochondrial stress response, can severely compromise hematopoietic stem cell (HSC) regeneration. Here we show that the NAD-boosting agent nicotinamide riboside (NR) reduces mitochondrial activity within HSCs through increased mitochondrial clearance, leading to increased asymmetric HSC divisions. NR dietary supplementation results in a significantly enlarged pool of progenitors, without concurrent HSC exhaustion, improves survival by 80%, and accelerates blood recovery after murine lethal irradiation and limiting-HSC transplantation. In immune-deficient mice, NR increased the production of human leucocytes from hCD34+ progenitors. Our work demonstrates for the first time a positive effect of NAD-boosting strategies on the most primitive blood stem cells, establishing a link between HSC mitochondrial stress, mitophagy, and stem-cell fate decision, and unveiling the potential of NR to improve recovery of patients suffering from hematological failure including post chemo- and radiotherapy.
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http://dx.doi.org/10.1016/j.stem.2019.02.012DOI Listing
March 2019

SMiLE-seq identifies binding motifs of single and dimeric transcription factors.

Nat Methods 2017 03 16;14(3):316-322. Epub 2017 Jan 16.

Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

Resolving the DNA-binding specificities of transcription factors (TFs) is of critical value for understanding gene regulation. Here, we present a novel, semiautomated protein-DNA interaction characterization technology, selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq). SMiLE-seq is neither limited by DNA bait length nor biased toward strong affinity binders; it probes the DNA-binding properties of TFs over a wide affinity range in a fast and cost-effective fashion. We validated SMiLE-seq by analyzing 58 full-length human, mouse, and Drosophila TFs from distinct structural classes. All tested TFs yielded DNA-binding models with predictive power comparable to or greater than that of other in vitro assays. De novo motif discovery on all JUN-FOS heterodimers and several nuclear receptor-TF complexes provided novel insights into partner-specific heterodimer DNA-binding preferences. We also successfully analyzed the DNA-binding properties of uncharacterized human C2H2 zinc-finger proteins and validated several using ChIP-exo.
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http://dx.doi.org/10.1038/nmeth.4143DOI Listing
March 2017