Single Cell RNA Profiling Reveals Adipocyte to Macrophage Signaling Sufficient to Enhance Thermogenesis

ABSTRACTThe “browning” of inguinal white adipose tissue (iWAT) through increased abundance of thermogenic beige/brite adipocytes is induced by cold exposure and many other perturbations in association with beneficial systemic metabolic effects. Adipose browning is reported to require activation of sympathetic nerve fibers (SNF), aided by alternately activated macrophages within iWAT. Here we demonstrate the first example of a non-cell autonomous pathway for iWAT browning that is fully independent of SNF activity. Thus, the strong induction of thermogenic adipocytes prompted by deletion of adipocyte fatty acid synthase (iAdFASNKO mice) was unaffected by denervation or the deletion of SNF modulator Neuregulin-4. However, browning of iWAT in iAdFASNKO mice does require adipocyte cAMP/protein kinase A signaling, as it was blocked in adipocyte- selective Fasn/Gsα double KO mice. Single-cell transcriptomic analysis of iAdFASNKO mouse adipose stromal cells revealed increased macrophages displaying gene expression signatures of the alternately activated type. Mechanistically, depletion of such phagocytic immune cells in iAdFASNKO mice fully abrogated appearance of thermogenic adipocytes in iWAT. Altogether, these findings reveal an unexpected pathway of cAMP/PKA-dependent iWAT browning that is initiated by adipocyte signals and caused by macrophage-like cells independent of sympathetic neuron involvement.

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Device therapy of resistant hypertension

Orvosi Hetilap ◽

10.1556/oh.2013.29543 ◽

2013 ◽

Vol 154 (6) ◽

pp. 203-208 ◽

Cited By ~ 1

Author(s):

Gábor Simonyi ◽

J. Róbert Bedros ◽

Mihály Medvegy

Keyword(s):

Blood Pressure ◽

Cardiovascular Risk ◽

Resistant Hypertension ◽

Carotid Sinus ◽

Maximum Tolerated Dose ◽

Reduce Blood Pressure ◽

Nerve Fibers ◽

Uncontrolled Hypertension ◽

Sympathetic Nerve Fibers ◽

Treatment Of Hypertension

It is well known that hypertension is an independent cardiovascular risk factor. Treatment of hypertension frequently includes administration of three or more drugs. Resistant hypertension is defined when blood pressure remains above target value despite full doses (the patient’s maximum tolerated dose) of antihypertensive medication consisting of at least three different classes of drugs including a diuretic. Pharmacological treatment of hypertension is often unsuccessful despite the increasing number of drug combinations. Uncontrolled hypertension, however, increases the cardiovascular risk. Device treatment of resistant hypertension is currently testing two major fields. One of them the stimulation of baroreceptors in the carotid sinus and the other is radiofrequency ablation of sympathetic nerve fibers around renal arteries to reduce blood pressure in drug resistant hypertension. Orv. Hetil., 2013, 154, 203–208.

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Faculty Opinions recommendation of Sensory and sympathetic nerve fibers undergo sprouting and neuroma formation in the painful arthritic joint of geriatric mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.722719401.793505949 ◽

2015 ◽

Author(s):

Tony Yaksh

Keyword(s):

Sympathetic Nerve ◽

Nerve Fibers ◽

Arthritic Joint ◽

Sympathetic Nerve Fibers ◽

Neuroma Formation

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Faculty Opinions recommendation of Construction of developmental lineage relationships in the mouse mammary gland by single-cell RNA profiling.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732141789.793540970 ◽

2017 ◽

Author(s):

Ron Prywes

Keyword(s):

Mammary Gland ◽

Single Cell ◽

Mouse Mammary Gland ◽

Rna Profiling

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FlsnRNA-seq: protoplasting-free full-length single-nucleus RNA profiling in plants

Genome Biology ◽

10.1186/s13059-021-02288-0 ◽

2021 ◽

Vol 22 (1) ◽

Cited By ~ 2

Author(s):

Yanping Long ◽

Zhijian Liu ◽

Jinbu Jia ◽

Weipeng Mo ◽

Liang Fang ◽

...

Keyword(s):

Single Cell ◽

Cell Walls ◽

Large Scale ◽

Full Length ◽

Cell Level ◽

Root Cells ◽

Rna Profiling ◽

Different Types ◽

Long Read ◽

Single Nucleus

AbstractThe broad application of single-cell RNA profiling in plants has been hindered by the prerequisite of protoplasting that requires digesting the cell walls from different types of plant tissues. Here, we present a protoplasting-free approach, flsnRNA-seq, for large-scale full-length RNA profiling at a single-nucleus level in plants using isolated nuclei. Combined with 10x Genomics and Nanopore long-read sequencing, we validate the robustness of this approach in Arabidopsis root cells and the developing endosperm. Sequencing results demonstrate that it allows for uncovering alternative splicing and polyadenylation-related RNA isoform information at the single-cell level, which facilitates characterizing cell identities.

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Single-cell biology to decode the immune cellular composition of kidney inflammation

Cell and Tissue Research ◽

10.1007/s00441-021-03483-y ◽

2021 ◽

Author(s):

Yu Zhao ◽

Ulf Panzer ◽

Stefan Bonn ◽

Christian F. Krebs

Keyword(s):

Single Cell ◽

Cell Biology ◽

Computational Analysis ◽

Immune Cell ◽

Therapeutic Interventions ◽

Experimental Setup ◽

Disease Etiology ◽

Rna Profiling ◽

Immune Mediated ◽

Health And Disease

AbstractSingle-cell biology is transforming the ability of researchers to understand cellular signaling and identity across medical and biological disciplines. Especially for immune-mediated diseases, a single-cell look at immune cell subtypes, signaling, and activity might yield fundamental insights into the disease etiology, mechanisms, and potential therapeutic interventions. In this review, we highlight recent advances in the field of single-cell RNA profiling and their application to understand renal function in health and disease. With a focus on the immune system, in particular on T cells, we propose some key directions of understanding renal inflammation using single-cell approaches. We detail the benefits and shortcomings of the various technological approaches outlined and give advice on potential pitfalls and challenges in experimental setup and computational analysis. Finally, we conclude with a brief outlook into a promising future for single-cell technologies to elucidate kidney function.

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