Biology subjects

Loureiro, Z. Y.

Publications and source records attributed to Loureiro, Z. Y..

3 recordsLinked to original sources

bioRxiv2026

A Cell-Autonomous Cold Sensor Promotes Lipolysis Through Phase Separation

Temperature is a fundamental determinant of mammalian metabolism. The canonical cold-adaptation pathway involves cold sensing by peripheral sensory neurons, which activate sympathetic outflow, {beta}-adrenergic signaling, and lipolysis in adipose tissue. In contrast, we report here a cell-intrinsic mechanism by which physiologically relevant cooling temperatures (27-31 oC) enhance lipolysis in subcutaneous adipose tissue. Mechanistically, cooling drives liquid-liquid phase separation (LLPS) of perilipin 1 (PLIN1), the dominant lipid droplet coat protein, promoting its condensation and the local recruitment of PKA to the droplet surface. This spatial reorganization selectively amplified PKA-mediated perilipin 1 phosphorylation, CGI-58 release, and ATGL-dependent lipolysis. The process depends on the intrinsically disordered region (IDR) of perilipin1, where four aromatic residues, conserved in endotherms but not in ectotherms, are required for cooling-induced LLPS and lipolysis in vivo. Notably, targeted delivery of an LLPS-competent perilipin 1 variant to the inguinal adipose tissue of mice enhanced local lipolysis and reduced depot mass. Together, these findings uncover a cell-intrinsic thermosensitive mechanism that can tune lipolytic responsiveness, offering a possible strategy for targeted depot-selective fat reduction.

cell biology↗

bioRxiv2023

A distinct class of hematopoietic stem cells develop from the human yellow bone marrow

During aging, adipose tissue within the bone marrow expands while the trabecular red marrow contracts. The impact of these changes on blood cell formation remains unclear. To address this question, we performed single-cell and single-nuclei transcriptomic analysis on adipose-rich yellow bone marrow (BMY) and adipose-poor trabecular red marrow (BMR) from human subjects undergoing lower limb amputations. Surprisingly, we discovered two distinct hematopoietic niches, in which BMY contains a higher number of monocytes and progenitor cells expressing genes associated with inflammation. To further investigate these niches, we developed an in-vitro organoid system that maintains features of the human bone marrow. We find cells from BMY are distinct in their expression of the leptin receptor, and respond to leptin stimulation with enhanced proliferation, leading to increased monocyte production. These findings suggest that the age-associated expansion of bone marrow adipose tissue drives a pro-inflammatory state by stimulating monocyte production from a spatially distinct, leptin-responsive hematopoietic stem/progenitor cell population. SignificanceThis study reveals that adipose tissue within the human bone marrow is a niche for hematopoietic stem and progenitor cells that can give rise to pro-inflammatory monocytes through leptin signaling. Expansion of bone marrow adipose tissue with age and stress may thus underlie inflammageing.

developmental biology↗

bioRxiv2022

Canonical Wnt Signaling Maintains Human Mesenchymal Progenitor Cell Multipotency During Adipose Tissue Development

Tissue development and repair throughout life depends on the availability of multipotent mesenchymal stem/progenitor cells capable of differentiating into specialized cell types. How an appropriately sized pool of such multipotent progenitors is maintained under varied signals for tissue growth and repair is unknown. We addressed this question by monitoring fate trajectories of human adipose tissue-derived multipotent progenitor cells using single-cell transcriptomics. Homogenous multipotent progenitors underwent two distinct fate trajectories rapidly upon induction of adipose differentiation- one toward the adipocyte fate, and the other towards a distinct, non-differentiated state characterized by up-regulation of canonical Wnt target genes. Upon isolation, this latter cell population was able to resume proliferation and display multipotency. Using canonical Wnt agonists and antagonists we find Wnt signaling is required for the maintenance of this multipotent pool under differentiation stimulus. In vivo, these cells are retained in adipose tissue developed from human multipotent progenitor cells in immunocompromised mice, and their transcriptomic signature is detected in human adult adipose tissue. Our study reveals a previously unrecognized mechanism for maintaining a functional pool of human mesenchymal progenitor cells under conditions of differentiation pressure, driven by Wnt signaling.

developmental biology↗