Biology subjects

Farmer, S. R.

Publications and source records attributed to Farmer, S. R..

4 recordsLinked to original sources

bioRxiv2023

Pathological beige remodeling induced by cancer cachexia depends on the disease severity and involves mainly the trans-differentiation of mature white adipocytes

In cancer associated cachexia (CAC), white adipose tissue undergoes morphofunctional and inflammatory changes that lead to tissue dysfunction and remodeling. In addition to metabolic changes in white adipose tissues (WAT), adipose tissue atrophy has been implicated in several clinical complications and poor prognoses associated with cachexia. Adipocyte atrophy may be associated with increased beige remodeling in human CAC as evidenced by the "beige remodeling" observed in preclinical models of CAC. Even though beige remodeling is associated with CAC-induced WAT dysfunction, there are still some open questions regarding their cellular origins. In this study, we investigated the development of beige remodeling in CAC from a broader perspective. In addition, we used a grading system to identify the scAT as being affected by mice weight loss early and intensely. Using different in vitro and ex-vivo techniques, we demonstrated that Lewis LLC1 cells can induce a switch from white to beige adipocytes, which is specific to this type of tumor cell. During the more advanced stages of CAC, beige adipocytes are mainly formed from the transdifferentiation of cells. According to our results, humanizing the CAC classification system is an efficient approach to defining the onset of the syndrome in a more homogeneous manner. Pathological beige remodeling occurred early in the disease course and exhibited phenotypic characteristics specific to LLC cells secretomes. Developing therapeutic strategies that recruit beige adipocytes in vivo may be better guided by an understanding of the cellular origins of beige adipocytes emitted by CAC.

cell biology↗

bioRxiv2023

Adrenergic Reprogramming of Preexisting Adipogenic Trajectories Steer Naive Mural Cells Toward Beige Differentiation

In adult white adipose tissue, cold or {beta}3-adrenoceptor activation promotes the appearance of thermogenic beige adipocytes. Our comprehensive single-cell analysis revealed that these cells arise through the reprogramming of existing adipogenic trajectories, rather than from a single precursor. These trajectories predominantly arise from SM22-expressing vascular mural progenitor cells. Central in this transition is the activation of Adrb3 in mature adipocytes, leading to subsequent upregulation of Adrb1 in primed progenitors. Under thermoneutral conditions, synergistic activation of both Adrb3 and Adrb1 recapitulates the pattern of cold-induced SM22+ cell recruitment. Lipolysis-derived eicosanoids, specifically docosahexaenoic acid (DHA) and arachidonic acid (AA) prime these processes and in vitro, were sufficient to recapitulate progenitor cells priming. Collectively, our findings provide a robust model for cold-induced beige adipogenesis, emphasizing a profound relationship between mature adipocytes and mural cells during cold acclimation, and revealing the metabolic potential of this unique cellular reservoir.

cell biology↗

bioRxiv2021

Multidimensional Single-Nuclei RNA-Seq Reconstruction of Adipose Tissue Reveals Adipocyte Plasticity Underlying Thermogenic Response

Adipose tissue has been classified based on its morphology and function as white, brown, or beige / brite. It plays an essential role as a regulator of systemic metabolism through paracrine and endocrine signals. Recently, multiple adipocyte subtypes have been revealed using RNA sequencing technology, going beyond simply defined morphology but by their cellular origin, adaptation to metabolic stress, and plasticity. Here, we performed an in-depth analysis of publicly available single-nuclei RNAseq from adipose tissue and utilized a workflow template to characterize adipocyte plasticity, heterogeneity, and secretome profiles. The reanalyzed dataset led to the identification of different subtypes of adipocytes including three subpopulations of thermogenic adipocytes and provided a characterization of distinct transcriptional profiles along the adipocyte trajectory under thermogenic challenges. This study provides a useful resource for further investigations regarding mechanisms related to adipocyte plasticity and trans-differentiation. HighlightsMultidimensional transcriptome analysis at single-nucleus resolution recovers nuclei of cell types in adipose tissue Adaptative thermogenic response results in 3 distinct mature adipose cell types Single-nuclei transcriptomic-based secretome analysis reveals adipose cell-type-specific genes The in vivo trajectory of adipocyte plasticity for thermogenic response reveals sets of trans-differentiation genes Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/431320v2_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@291767org.highwire.dtl.DTLVardef@1bfa3b1org.highwire.dtl.DTLVardef@93e051org.highwire.dtl.DTLVardef@6bef5e_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2020

Single cell atlas of beige remodeling of white adipose tissue reveals a myeloid to lymphoid shift during cold exposure compared to beta 3 adrenergic stimulation

White adipose tissue (WAT) is a dynamic tissue, which responds to environmental stimuli and dietary cues by changing its morphology and metabolic capacity. The ability of WAT to undergo a beige remodeling has become an appealing strategy to combat obesity and its related metabolic complications. Within the cell mixture that constitutes the stromal vascular fraction (SVF), WAT beiging is initiated through expansion and differentiation of adipocytes progenitor cells, however, the extent of the SVF cellular changes is still poorly understood. Additionally, direct beta 3 adrenergic receptor (Adrb3) stimulation has been extensively used to mimic physiological cold- induced beiging, yet it is still unknown whether Adrb3 activation induces the same WAT remodeling as cold exposure. Here, by using single cell RNA sequencing, we provide a comprehensive atlas of the cellular dynamics during beige remodeling within white adipose tissue. We reveal drastic changes both in the overall cellular composition and transcriptional states of individual cell subtypes between Adrb3- and cold-induced beiging. Moreover, we demonstrate that cold exposure induces a myeloid to lymphoid shift of the immune compartment compared to Adrb3 activation. Further analysis, showed that Adrb3 stimulation leads to activation of the interferon/Stat1 pathways favoring infiltration of myeloid immune cells, while repression of this pathway by cold promotes lymphoid immune cells recruitment. These findings provide new insight into the cellular dynamics during WAT beige remodeling and could ultimately lead to novel strategies to identify translationally-relevant drug targets to counteract obesity and T2D.

cell biology↗