Single-cell transcriptomics reveals maturation of transplanted stem cell–derived retinal pigment epithelial cells toward native state DOI Creative Commons
Bhav Harshad Parikh, Paul Blakeley,

Kakkad Regha

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(26)

Published: June 20, 2023

Transplantation of stem cell–derived retinal pigment epithelial (RPE) cells is considered a viable therapeutic option for age-related macular degeneration (AMD). Several landmark Phase I/II clinical trials have demonstrated safety and tolerability RPE transplants in AMD patients, albeit with limited efficacy. Currently, there understanding how the recipient retina regulates survival, maturation, fate specification transplanted cells. To address this, we into subretinal space immunocompetent rabbits 1 mo conducted single-cell RNA sequencing analyses on explanted monolayers, compared to their age-matched vitro counterparts. We observed an unequivocal retention identity, trajectory-inferred survival all populations after transplantation. Furthermore, was unidirectional maturation toward native adult human state RPE, regardless cell resource. Gene regulatory network analysis suggests that tripartite transcription factors ( FOS , JUND MAFF ) may be specifically activated posttransplanted cells, regulate canonical signature gene expression crucial supporting host photoreceptor function, prosurvival genes required RPE’s adaptation microenvironment. These findings shed insights transcriptional landscape transplantation, important implications cell-based therapy AMD.

Language: Английский

The morphological and functional diversity of apical microvilli DOI Open Access
Maria Sharkova, Erica Chow, Timothy Erickson

et al.

Journal of Anatomy, Journal Year: 2022, Volume and Issue: 242(3), P. 327 - 353

Published: Oct. 25, 2022

Abstract Sensory neurons use specialized apical processes to perceive external stimuli and monitor internal body conditions. The apparatus can include cilia, microvilli, or both, is adapted for the functions of particular cell type. Photoreceptors detect light through a large, modified cilium (outer segment), that supported by surrounding ring microvilli‐like calyceal (CPs). Although first reported 150 years ago, CPs remain poorly understood. As basis future study, we therefore conducted review existing literature about sensory which act either as primary detector support cilia‐based detector. While all microvilli are finger‐like cellular protrusions with an actin core, vary across types in size, number, arrangement, dynamics, function. We summarize current state knowledge characteristics found on inner ear hair cells (stereocilia) cerebral spinal fluid‐contacting neurons, comparisons brush border intestinal renal epithelia. structure, stability, dynamics core regulated complement actin‐binding proteins, includes both common components unique features when compared types. Further, often lateral links, glycocalyx, defined extracellular matrix, each function environment cell. Our comparison microvillar will inform further research into how photoreceptor function, also provide general investigations structure neurons.

Language: Английский

Citations

25

CD44 signaling in Müller cells impacts photoreceptor function and survival in healthy and diseased retinas DOI Creative Commons

Monika Ayten,

Tobias Straub, Lew Kaplan

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Aug. 2, 2024

Abstract Retinitis pigmentosa (RP), an inherited retinal disease, affects 1,5 million people worldwide. The initial mutation-driven photoreceptor degeneration leads to chronic inflammation, characterized by Müller cell activation and upregulation of CD44. CD44 is a surface transmembrane glycoprotein the primary receptor for hyaluronic acid. It involved in many pathological processes, but little known about CD44’s functions. expression also increased cells from our Pde6b STOP/STOP RP mouse model. To gain more detailed understanding role healthy diseased retinas, we analyzed Cd44 −/− mice, respectively. loss led enhanced degeneration, reduced function, inflammatory response. understand underlying mechanism, performed proteomic analysis on isolated retinas identified significant downregulation glutamate transporter 1 (SLC1A2). This was accompanied higher levels, suggesting impaired homeostasis. These novel findings indicate that stimulates uptake via SLC1A2 cells, which turn, supports survival function.

Language: Английский

Citations

5

Extracellular matrix component expression in human pluripotent stem cell-derived retinal organoids recapitulates retinogenesis in vivo and reveals an important role for IMPG1 and CD44 in the development of photoreceptors and interphotoreceptor matrix DOI Creative Commons
Majed Felemban, Birthe Dorgau, Nicola C. Hunt

et al.

Acta Biomaterialia, Journal Year: 2018, Volume and Issue: 74, P. 207 - 221

Published: May 17, 2018

The extracellular matrix (ECM) plays an important role in numerous processes including cellular proliferation, differentiation, migration, maturation, adhesion guidance and axonal growth. To date, there has been no detailed analysis of the ECM distribution during retinal ontogenesis humans functional importance many components is poorly understood. In this study, expression key adult mouse monkey retina, developing human retina organoids derived from pluripotent stem cells was studied. Our data indicate that basement membrane ECMs (Fibronectin Collagen IV) were expressed Bruch's inner limiting whilst hyalectins (Versican Brevican), cluster differentiation 44 (CD44), photoreceptor-specific Interphotoreceptor Matrix Proteoglycan 1 (IMPG1) 2 (IMPG2) detected interphotoreceptor (IPM). IMPG1, Versican Brevican IPM conserved between cell-derived organoids. Blocking action CD44 IMPG1 cell affected development photoreceptors, their inner/outer segments connecting cilia disrupted formation, with having earlier more significant impact. Together, our suggest for photoreceptors formation retinogenesis. not fully (Collagen IV, Fibronectin, Brevican, Versican, IMPG2) investigated ontogenesis. IV Fibronectin membrane; whereas & IMPG2 Retinal successfully generated cells. examined found to recapitulate vivo. Using blocking experiments, we able highlight formation.

Language: Английский

Citations

40

Genomics of Secondarily Temperate Adaptation in the Only Non-Antarctic Icefish DOI Creative Commons
Angel G. Rivera‐Colón, Niraj Rayamajhi, Bushra Fazal Minhas

et al.

Molecular Biology and Evolution, Journal Year: 2023, Volume and Issue: 40(3)

Published: Feb. 21, 2023

Abstract White-blooded Antarctic icefishes, a family within the adaptive radiation of notothenioid fishes, are an example extreme biological specialization to both chronic cold Southern Ocean and life without hemoglobin. As result, icefishes display derived physiology that limits them highly oxygenated waters. Against these constraints, remarkably one species, pike icefish Champsocephalus esox, successfully colonized temperate South American To study genetic mechanisms underlying secondarily adaptation in we generated chromosome-level genome assemblies C. esox its sister gunnari. The is similar structure organization congener; however, observe evidence chromosomal rearrangements coinciding with regions elevated divergence populations. We also find several key pathways under selection, including genes related mitochondria vision, highlighting candidates behind esox. Substantial antifreeze glycoprotein (AFGP) pseudogenization has occurred icefish, likely due relaxed selection following ancestral escape from Antarctica. canonical AFGP locus conserved gunnari, but show translocation two copies separate locus, previously unobserved cryonotothenioids. Altogether, this species provides insight into ecologically disparate environments otherwise specialized group.

Language: Английский

Citations

13

Single-cell transcriptomics reveals maturation of transplanted stem cell–derived retinal pigment epithelial cells toward native state DOI Creative Commons
Bhav Harshad Parikh, Paul Blakeley,

Kakkad Regha

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(26)

Published: June 20, 2023

Transplantation of stem cell–derived retinal pigment epithelial (RPE) cells is considered a viable therapeutic option for age-related macular degeneration (AMD). Several landmark Phase I/II clinical trials have demonstrated safety and tolerability RPE transplants in AMD patients, albeit with limited efficacy. Currently, there understanding how the recipient retina regulates survival, maturation, fate specification transplanted cells. To address this, we into subretinal space immunocompetent rabbits 1 mo conducted single-cell RNA sequencing analyses on explanted monolayers, compared to their age-matched vitro counterparts. We observed an unequivocal retention identity, trajectory-inferred survival all populations after transplantation. Furthermore, was unidirectional maturation toward native adult human state RPE, regardless cell resource. Gene regulatory network analysis suggests that tripartite transcription factors ( FOS , JUND MAFF ) may be specifically activated posttransplanted cells, regulate canonical signature gene expression crucial supporting host photoreceptor function, prosurvival genes required RPE’s adaptation microenvironment. These findings shed insights transcriptional landscape transplantation, important implications cell-based therapy AMD.

Language: Английский

Citations

13