Single-Cell Transcriptomics and Lineage Tracing Unveil Parallels in Lymphatic Muscle and Venous Smooth Muscle Development, Identity, and Function

Arteriosclerosis Thrombosis and Vascular Biology, Год журнала: 2025, Номер unknown

Опубликована: Май 15, 2025

BACKGROUND: Lymphatic muscle cells (LMCs) are indispensable for lymphatic vessel contraction, and their aberrant recruitment or absence is associated with both primary secondary lymphedema. Despite critical role in function, the cellular molecular bases that confer unique contractile properties to LMCs largely undefined, limiting development of therapeutic interventions precisely target LMCs. METHODS: We used single-cell RNA sequencing, genetic lineage tracing, whole mount immunostaining, intravital imaging investigate basis hybrid cardiomyocyte blood vascular smooth cell (SMC) characteristics have been described RESULTS: Using transcriptomes venous SMCs exhibited more similarities than differences, types exhibiting enrichment overlapping markers. Notably, were markedly distinct from arteriole SMCs. Functionally, vessels murine hind limb displayed pulsatile contractility, functions regulated by gabapentin nifedipine, which activity voltage-gated calcium channels. Although express genes overlap SMC transcriptome, tracing demonstrates do not originate Myh11 (myosin heavy chain 11) lineage-derived SMCs, Nkx2.5 (NK2 homeobox 5) progenitors, Wnt1 (Wnt family member 1) neural crest progenitors. Instead, most inguinal-axillary region WT1 + (Wilms tumor gene mesodermal progenitors lateral plate mesoderm. derived maintenance contractility. CONCLUSIONS: Overall, our findings suggest derive a related progenitor acquire similar expression program facilitates properties.

Язык: Английский

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Regulation of Collecting Lymphatic Vessel Contractile Function by TRPV4 Channels

Arteriosclerosis Thrombosis and Vascular Biology, Год журнала: 2025, Номер unknown

Опубликована: Май 15, 2025

BACKGROUND: Dysregulation of TRPV4 (transient receptor potential vanilloid 4)–mediated signaling has been associated with inflammation and tissue fibrosis, both which are key features in the pathophysiology lymphatic system diseases; however, expression functional roles channels remain largely unexplored. METHODS: We generated a single-cell RNA sequencing dataset from microdissected mouse collecting vessels to characterize Trpv4 . Using novel fx/fx strain Cre-lines Prox1 - CreER T2 LysM-Cre we assessed role endothelial cells peri-lymphatic myeloid cells, respectively. Confocal microscopy extensive experimentation on isolated pressurized lymphatics, including measurements intracellular calcium activity, were used validate our findings elucidate underlying mechanisms. Clinical significance was using biopsies patients breast cancer–related lymphedema. RESULTS: characterized transcriptome surrounding tissues. highly enriched subset Lyve1 + (lymphatic vessel hyaluronan 1) macrophages displaying tissue-resident profile. In clinical samples, lymphedema increased infiltration coexpressing LYVE1 TRPV4. Pharmacological activation led contractile dysregulation lymphatics. The response multiphasic, initial vasospasm subsequent vasodilation inhibition contractions, TXA2Rs (thromboxane A2 receptors) muscle by secreted prostanoids TRPV4+ nitric oxide (and perhaps other vasodilatory prostanoids) cells. TXA2R-mediated resulted mobilization stores through inositol trisphosphate receptors store-operated entry. CONCLUSIONS: Our results uncovered mechanism mediated crosstalk between TRPV4-expressing LYVE1+ macrophages, or These highlight potentially important dysfunction inflammation, secondary

Язык: Английский

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Risk factors for severity of breast cancer-related lymphedema

Radiation Oncology, Год журнала: 2025, Номер 20(1)

Опубликована: Май 20, 2025

Язык: Английский

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Increased CSF drainage by non-invasive manipulation of cervical lymphatics

Nature, Год журнала: 2025, Номер unknown

Опубликована: Июнь 4, 2025

Язык: Английский

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