Atf3 defines a population of pulmonary endothelial cells essential for lung regeneration DOI Creative Commons
Terren K. Niethamer, Lillian Levin, Michael P. Morley

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Oct. 14, 2022

Abstract Following acute injury, the capillary vascular bed in lung must be repaired to reestablish gas exchange with external environment. Little is known about transcriptional and signaling factors that drive pulmonary endothelial cell (EC) proliferation subsequent regeneration of capillaries, as well their response stress. Here, we show transcription factor Atf3 essential for regenerative mouse endothelium after influenza infection. expression defines a subpopulation ECs enriched genes involved development, differentiation, migration. During alveolar regeneration, this EC population expands increases angiogenesis, blood vessel cellular Importantly, cell-specific loss results defective part through increased apoptosis decreased endothelium. This leads general persistent morphological changes niche, including an emphysema-like phenotype enlarged airspaces lined regions lack investment. Taken together, these data implicate component injury required successful regeneration.

Language: Английский

The Transcription Factor Ets1 Influences Axonal Growth via Regulation of Lcn2 DOI Creative Commons

Miao Gu,

Xiaodi Li, Ronghua Wu

et al.

Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 61(2), P. 971 - 981

Published: Sept. 6, 2023

Abstract Transcription factors are essential for the development and regeneration of nervous system. The current study investigated key regulatory transcription in rat spinal cord via RNA sequencing. hub gene Ets1 was highly expressed during embryonic period, then its expression decreased development. Knockdown significantly increased axonal growth cultured neurons. Luciferase reporter assays chromatin immunoprecipitation indicated that could directly bind to Lcn2 promoter positively regulate transcription. In conclusion, these findings provide first direct evidence regulates axon by controlling expression, may be a novel therapeutic target central

Language: Английский

Citations

3

Activating Transcription Factor 3 Stimulates Follicle-Stimulating Hormone-β Expression In Vitro But Is Dispensable for Follicle-Stimulating Hormone Production in Murine Gonadotropes In Vivo DOI
Carlos Alonso,

Caroline D David,

Chirine Toufaily

et al.

Endocrinology, Journal Year: 2023, Volume and Issue: 164(5)

Published: March 13, 2023

Follicle-stimulating hormone (FSH), a dimeric glycoprotein produced by pituitary gonadotrope cells, regulates spermatogenesis in males and ovarian follicle growth females. Hypothalamic gonadotropin-releasing (GnRH) stimulates FSHβ subunit gene (Fshb) transcription, though the underlying mechanisms are poorly understood. To address this gap knowledge, we examined changes expression GnRH-deficient mice (hpg) treated with regimen of exogenous GnRH that increases Fshb but not luteinizing β (Lhb) messenger RNA levels. Activating transcription factor 3 (Atf3) was among most upregulated genes. (ATF3) can heterodimerize members activator protein 1 family to regulate transcription. Co-expression ATF3 JunB stimulated murine Fshb, Lhb, promoter-reporter activity homologous LβT2b cells. also synergized constitutively active activin type I receptor increase endogenous these Nevertheless, FSH production intact gonadotrope-specific Atf3 knockout [conditional (cKO)] mice. Ovarian development, ovulation, litter sizes were equivalent between cKOs controls. Testis weights sperm counts did differ genotypes. Following gonadectomy, LH secretion enhanced cKO animals. Though levels genotypes, post-gonadectomy gonadotropin α more pronounced than control These data indicate selectively stimulate vitro is required for vivo.

Language: Английский

Citations

2

Lampreys and spinal cord regeneration: “a very special claim on the interest of zoologists,” 1830s-present DOI Creative Commons
Kathryn Maxson Jones, Jennifer R. Morgan

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: May 9, 2023

Employing history of science methods, including analyses the scientific literature, archival documents, and interviews with scientists, this paper presents a lampreys in neurobiology from 1830s to present. We emphasize lamprey’s roles helping elucidate spinal cord regeneration mechanisms. Two attributes have long perpetuated studies neurobiology. First, they possess large neurons, multiple classes stereotypically located, ‘identified’ giant neurons brain, which project their axons into cord. These axonal fibers facilitated electrophysiological recordings imaging across biological scales, ranging molecular circuit-level nervous system structures functions behavioral output. Second, been considered amongst most basal extant vertebrates on planet, so comparative pointing conserved derived characteristics vertebrate systems. features attracted neurologists zoologists between 1930s. But, same two also rise lamprey neural research after 1959, when biologists first wrote about spontaneous, robust some identified CNS larvae injuries, coupled recovery normal swimming. Not only did promote fresh insights field, enabling incorporating scales existing new technologies. But investigators were able attach broad scope relevance studies, interpreting them as suggesting successful, sometimes even unsuccessful, regeneration. Lamprey demonstrated that functional takes place without reformation original neuronal connections, for instance, by way imperfect regrowth compensatory plasticity. Moreover, performed model revealed factors intrinsic are integral promoting or hindering As work has helped illuminate why accomplish well, whereas mammals do it poorly, case study how medical value been, could continue be, gleaned non-traditional organism tools developed relatively recently.

Language: Английский

Citations

2

Differential Retinal Ganglion Cell Vulnerability, A Critical Clue for the Identification of Neuroprotective Genes in Glaucoma DOI Creative Commons

Dwarkesh Amin,

Takaaki Kuwajima

Frontiers in Ophthalmology, Journal Year: 2022, Volume and Issue: 2

Published: May 31, 2022

Retinal ganglion cells (RGCs) are the neurons in retina which directly project to brain and transmit visual information along optic nerve. Glaucoma, one of leading causes blindness, is characterized by elevated intraocular pressure (IOP) degeneration nerve, followed RGC death. Currently, there no clinical therapeutic drugs or molecular interventions that prevent death outside IOP reduction. In order overcome these major barriers, an increased number studies have utilized following combined analytical methods: well-established rodent models glaucoma including nerve injury transcriptomic gene expression profiling, resulting successful identification molecules signaling pathways relevant protection. this review, we present a comprehensive overview pathological features variety animal top differentially expressed genes (DEGs) depending on disease progression, subtypes, retinal regions species. By comparing DEGs among those different transcriptome profiles, discuss whether commonly listed could be defined as potential novel targets glaucoma, will facilitate development future neuroprotective strategies for treatments human patients glaucoma.

Language: Английский

Citations

4

Atf3 defines a population of pulmonary endothelial cells essential for lung regeneration DOI Creative Commons
Terren K. Niethamer, Lillian Levin, Michael P. Morley

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Oct. 14, 2022

Abstract Following acute injury, the capillary vascular bed in lung must be repaired to reestablish gas exchange with external environment. Little is known about transcriptional and signaling factors that drive pulmonary endothelial cell (EC) proliferation subsequent regeneration of capillaries, as well their response stress. Here, we show transcription factor Atf3 essential for regenerative mouse endothelium after influenza infection. expression defines a subpopulation ECs enriched genes involved development, differentiation, migration. During alveolar regeneration, this EC population expands increases angiogenesis, blood vessel cellular Importantly, cell-specific loss results defective part through increased apoptosis decreased endothelium. This leads general persistent morphological changes niche, including an emphysema-like phenotype enlarged airspaces lined regions lack investment. Taken together, these data implicate component injury required successful regeneration.

Language: Английский

Citations

4