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Identification and characterization of early human photoreceptor states and cell-state-specific retinoblastoma-related features.
Shayler, Dominic W H; Stachelek, Kevin; Cambier, Linda; Lee, Sunhye; Bai, Jinlun; Reid, Mark W; Weisenberger, Daniel J; Bhat, Bhavana; Aparicio, Jennifer G; Kim, Yeha; Singh, Mitali; Bay, Maxwell; Thornton, Matthew E; Doyle, Eamon K; Fouladian, Zachary; Erberich, Stephan G; Grubbs, Brendan H; Bonaguidi, Michael A; Craft, Cheryl Mae; Singh, Hardeep P; Cobrinik, David.
  • Shayler DWH; The Vision Center, Department of Surgery, and Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
  • Stachelek K; Development, Stem Cell, and Regenerative Medicine Program, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Cambier L; The Vision Center, Department of Surgery, and Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
  • Lee S; Cancer Biology and Genomics Program, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Bai J; The Vision Center, Department of Surgery, and Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
  • Reid MW; The Vision Center, Department of Surgery, and Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
  • Weisenberger DJ; The Vision Center, Department of Surgery, and Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
  • Bhat B; Development, Stem Cell, and Regenerative Medicine Program, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Aparicio JG; The Vision Center, Department of Surgery, and Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
  • Kim Y; Department of Biochemistry & Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Singh M; Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Bay M; The Vision Center, Department of Surgery, and Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
  • Thornton ME; The Vision Center, Department of Surgery, and Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
  • Doyle EK; The Vision Center, Department of Surgery, and Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
  • Fouladian Z; The Vision Center, Department of Surgery, and Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
  • Erberich SG; Development, Stem Cell, and Regenerative Medicine Program, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Grubbs BH; Maternal-Fetal Medicine Division of the Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Bonaguidi MA; Department of Radiology and The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
  • Craft CM; Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Singh HP; The Vision Center, Department of Surgery, and Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.
  • Cobrinik D; Development, Stem Cell, and Regenerative Medicine Program, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
bioRxiv ; 2024 Aug 22.
Article en En | MEDLINE | ID: mdl-38915659
ABSTRACT
Human cone photoreceptors differ from rods and serve as the retinoblastoma cell-of-origin, yet the developmental basis for their distinct behaviors is poorly understood. Here, we used deep full-length single-cell RNA-sequencing to distinguish post-mitotic cone and rod developmental states and identify cone-specific features that contribute to retinoblastomagenesis. The analyses revealed early post-mitotic cone- and rod-directed populations characterized by higher THRB or NRL regulon activities, an immature photoreceptor precursor population with concurrent cone and rod gene and regulon expression, and distinct early and late cone and rod maturation states distinguished by maturation-associated declines in RAX regulon activity. Unexpectedly, both L/M cone and rod precursors co-expressed NRL and THRB RNAs, yet they differentially expressed functionally antagonistic NRL and THRB isoforms and prematurely terminated THRB transcripts. Early L/M cone precursors exhibited successive expression of several lncRNAs along with MYCN, which composed the seventh most L/M-cone-specific regulon, and SYK, which contributed to the early cone precursors' proliferative response to RB1 loss. These findings reveal previously unrecognized photoreceptor precursor states and a role for early cone-precursor-intrinsic SYK expression in retinoblastoma initiation.
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Texto completo: 1 Banco de datos: MEDLINE Idioma: En Año: 2024 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Idioma: En Año: 2024 Tipo del documento: Article