Transcriptomic Analysis Reveals That Excessive Thyroid Hormone Signaling Impairs Phototransduction and Mitochondrial Bioenergetics and Induces Cellular Stress in Mouse Cone Photoreceptors DOI Open Access
Hongwei Ma, David R. Stanford, Willard M. Freeman

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7435 - 7435

Published: July 6, 2024

Thyroid hormone (TH) plays an essential role in cell proliferation, differentiation, and metabolism. Experimental clinical studies have shown a potential association between TH signaling retinal degeneration. The suppression of protects cone photoreceptors mouse models degeneration, whereas excessive induces manifested as reduced light response loss cones. This work investigates the genes/transcriptomic alterations that might be involved TH-induced degeneration mice using single-cell RNA sequencing (scRNAseq) analysis. One-month-old C57BL/6 received triiodothyronine (T3, 20 µg/mL drinking water) for 4 weeks model hyperthyroidism/excessive signaling. At end experiments, cells were dissociated, viability was analyzed before being subjected to scRNAseq. resulting data Seurat package visualized Loupe browser. Among 155,866 single cells, we identified 14 clusters, representing various types, with rod clusters comprising 76% 4.1% total population, respectively. Cone cluster transcriptomes demonstrated most after T3 treatment, 450 differentially expressed genes (DEGs), accounting 38.5% DEGs. Statistically significant changes expression revealed phototransduction oxidative phosphorylation impaired along mitochondrial dysfunction. A pathway analysis also showed activation sensory neuronal/photoreceptor stress pathways treatment. Specifically, eukaryotic initiation factor-2 cAMP element-binding protein upregulated. Thus, substantially affects cones at transcriptomic level. findings from this provide insight into how

Language: Английский

NADase CD38 is a key determinant of ovarian aging DOI Creative Commons
Qingling Yang, Wenhui Chen, Luping Cong

et al.

Nature Aging, Journal Year: 2023, Volume and Issue: 4(1), P. 110 - 128

Published: Dec. 21, 2023

Abstract The ovary ages earlier than most other tissues, yet the underlying mechanisms remain elusive. Here a comprehensive analysis of transcriptomic landscapes in different organs young and middle-aged mice revealed that ovaries showed expression age-associated genes, identifying increased NADase CD38 decreased NAD + levels mice. Bulk single-cell RNA sequencing deletion mitigated ovarian aging, preserving fertility follicle reserve aged by countering age-related gene changes intercellular communication alterations. Mechanistically, onset inflammation induced higher ovary, thereby accelerating aging. Consistently, pharmacological inhibition enhanced Our findings aging relative to organs, providing potential therapeutic target for ameliorating female infertility.

Language: Английский

Citations

33

Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics DOI Creative Commons

Huifen Lu,

Ying Jing, Chen Zhang

et al.

Protein & Cell, Journal Year: 2023, Volume and Issue: 15(5), P. 364 - 384

Published: Dec. 21, 2023

The ovary is indispensable for female reproduction, and its age-dependent functional decline the primary cause of infertility. However, molecular basis ovarian aging in higher vertebrates remains poorly understood. Herein, we apply spatiotemporal transcriptomics to benchmark architecture organization as well cellular determinants young primate ovaries compare these aged ovaries. From a global view, somatic cells within non-follicle region undergo more pronounced transcriptional fluctuation relative those follicle region, likely constituting hostile microenvironment that facilitates aging. Further, uncovered inflammation, senescent-associated secretory phenotype, senescence, fibrosis are contributors (PCOA). Of note, identified spatial co-localization between PCOA-featured spot an unappreciated MT2 (Metallothionein 2) highly expressing (MT2high) characterized by high levels potentially serving hotspot ovary. Moreover, with advanced age, subpopulation MT2high accumulates, disseminating amplifying senescent signal outward. Our study establishes first transcriptomic atlas, advancing our understanding mechanistic underpinning unraveling potential biomarkers therapeutic targets age-associated human disorders.

Language: Английский

Citations

19

Analysis of cell–cell interaction between mural granulosa cells and cumulus granulosa cells during ovulation using single‐cell RNA sequencing data of mouse ovary DOI
Yuichiro Shirafuta, Isao Tamura,

Amon Shiroshita

et al.

Reproductive Medicine and Biology, Journal Year: 2024, Volume and Issue: 23(1)

Published: Jan. 1, 2024

We investigated the interactions between mural granulosa cells (MGCs) and cumulus (CGCs) during ovulation after LH surge.

Language: Английский

Citations

6

Transcriptomic Analysis Reveals That Excessive Thyroid Hormone Signaling Impairs Phototransduction and Mitochondrial Bioenergetics and Induces Cellular Stress in Mouse Cone Photoreceptors DOI Open Access
Hongwei Ma, David R. Stanford, Willard M. Freeman

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7435 - 7435

Published: July 6, 2024

Thyroid hormone (TH) plays an essential role in cell proliferation, differentiation, and metabolism. Experimental clinical studies have shown a potential association between TH signaling retinal degeneration. The suppression of protects cone photoreceptors mouse models degeneration, whereas excessive induces manifested as reduced light response loss cones. This work investigates the genes/transcriptomic alterations that might be involved TH-induced degeneration mice using single-cell RNA sequencing (scRNAseq) analysis. One-month-old C57BL/6 received triiodothyronine (T3, 20 µg/mL drinking water) for 4 weeks model hyperthyroidism/excessive signaling. At end experiments, cells were dissociated, viability was analyzed before being subjected to scRNAseq. resulting data Seurat package visualized Loupe browser. Among 155,866 single cells, we identified 14 clusters, representing various types, with rod clusters comprising 76% 4.1% total population, respectively. Cone cluster transcriptomes demonstrated most after T3 treatment, 450 differentially expressed genes (DEGs), accounting 38.5% DEGs. Statistically significant changes expression revealed phototransduction oxidative phosphorylation impaired along mitochondrial dysfunction. A pathway analysis also showed activation sensory neuronal/photoreceptor stress pathways treatment. Specifically, eukaryotic initiation factor-2 cAMP element-binding protein upregulated. Thus, substantially affects cones at transcriptomic level. findings from this provide insight into how

Language: Английский

Citations

1