An integrated transcriptional analysis of the developing human retina

Carla B. Mellough, Roman Bauer, Joseph Collin, Birthe Dorgau, Darin Zerti, David W. P. Dolan, Carl M. Jones, Osagie G. Izuogu, Min Yu, Dean Hallam, Jannetta S. Steyn, Kathryn Whites, David H. Steel, Mauro Santibanez-Koref, David J. Elliott, Michael S. Jackson, Susan Lindsay, Sushma Grellscheid, Majlinda Lako

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The scarcity of embryonic/foetal material as a resource for direct study means that there is still limited understanding of human retina development. Here, we present an integrated transcriptome analysis combined with immunohistochemistry in human eye and retinal samples from 4 to 19 post-conception weeks. This analysis reveals three developmental windows with specific gene expression patterns that informed the sequential emergence of retinal cell types and enabled identification of stage-specific cellular and biological processes, and transcriptional regulators. Each stage is characterised by a specific set of alternatively spliced transcripts that code for proteins involved in the formation of the photoreceptor connecting cilium, pre-mRNA splicing and epigenetic modifiers. Importantly, our data show that the transition from foetal to adult retina is characterised by a large increase in the percentage of mutually exclusive exons that code for proteins involved in photoreceptor maintenance. The circular RNA population is also defined and shown to increase during retinal development. Collectively, these data increase our understanding of human retinal development and the pre-mRNA splicing process, and help to identify new candidate disease genes.

Original languageEnglish
Article number169474
Number of pages16
JournalDevelopment
Volume146
Issue number2
DOIs
Publication statusPublished - 15 Jan 2019

Cite this

Mellough, C. B., Bauer, R., Collin, J., Dorgau, B., Zerti, D., Dolan, D. W. P., ... Lako, M. (2019). An integrated transcriptional analysis of the developing human retina. Development, 146(2), [169474]. https://doi.org/10.1242/dev.169474
Mellough, Carla B. ; Bauer, Roman ; Collin, Joseph ; Dorgau, Birthe ; Zerti, Darin ; Dolan, David W. P. ; Jones, Carl M. ; Izuogu, Osagie G. ; Yu, Min ; Hallam, Dean ; Steyn, Jannetta S. ; Whites, Kathryn ; Steel, David H. ; Santibanez-Koref, Mauro ; Elliott, David J. ; Jackson, Michael S. ; Lindsay, Susan ; Grellscheid, Sushma ; Lako, Majlinda. / An integrated transcriptional analysis of the developing human retina. In: Development. 2019 ; Vol. 146, No. 2.
@article{01e8c46fbb2642e6bce706367627c196,
title = "An integrated transcriptional analysis of the developing human retina",
abstract = "The scarcity of embryonic/foetal material as a resource for direct study means that there is still limited understanding of human retina development. Here, we present an integrated transcriptome analysis combined with immunohistochemistry in human eye and retinal samples from 4 to 19 post-conception weeks. This analysis reveals three developmental windows with specific gene expression patterns that informed the sequential emergence of retinal cell types and enabled identification of stage-specific cellular and biological processes, and transcriptional regulators. Each stage is characterised by a specific set of alternatively spliced transcripts that code for proteins involved in the formation of the photoreceptor connecting cilium, pre-mRNA splicing and epigenetic modifiers. Importantly, our data show that the transition from foetal to adult retina is characterised by a large increase in the percentage of mutually exclusive exons that code for proteins involved in photoreceptor maintenance. The circular RNA population is also defined and shown to increase during retinal development. Collectively, these data increase our understanding of human retinal development and the pre-mRNA splicing process, and help to identify new candidate disease genes.",
keywords = "Developing human retina, Transcriptome, Immunohistochemistry, Alternative splicing, Retinal cells, Circular RNAs, CELL FATE SPECIFICATION, CIRCULAR RNAS, HOMEOBOX GENE, OPTIC-NERVE, HUMAN FOVEA, EXPRESSION, FETAL, EYE, DIFFERENTIATION, PAX6",
author = "Mellough, {Carla B.} and Roman Bauer and Joseph Collin and Birthe Dorgau and Darin Zerti and Dolan, {David W. P.} and Jones, {Carl M.} and Izuogu, {Osagie G.} and Min Yu and Dean Hallam and Steyn, {Jannetta S.} and Kathryn Whites and Steel, {David H.} and Mauro Santibanez-Koref and Elliott, {David J.} and Jackson, {Michael S.} and Susan Lindsay and Sushma Grellscheid and Majlinda Lako",
year = "2019",
month = "1",
day = "15",
doi = "10.1242/dev.169474",
language = "English",
volume = "146",
journal = "Development",
issn = "0950-1991",
publisher = "The Company of Biologists",
number = "2",

}

Mellough, CB, Bauer, R, Collin, J, Dorgau, B, Zerti, D, Dolan, DWP, Jones, CM, Izuogu, OG, Yu, M, Hallam, D, Steyn, JS, Whites, K, Steel, DH, Santibanez-Koref, M, Elliott, DJ, Jackson, MS, Lindsay, S, Grellscheid, S & Lako, M 2019, 'An integrated transcriptional analysis of the developing human retina' Development, vol. 146, no. 2, 169474. https://doi.org/10.1242/dev.169474

An integrated transcriptional analysis of the developing human retina. / Mellough, Carla B.; Bauer, Roman; Collin, Joseph; Dorgau, Birthe; Zerti, Darin; Dolan, David W. P.; Jones, Carl M.; Izuogu, Osagie G.; Yu, Min; Hallam, Dean; Steyn, Jannetta S.; Whites, Kathryn; Steel, David H.; Santibanez-Koref, Mauro; Elliott, David J.; Jackson, Michael S.; Lindsay, Susan; Grellscheid, Sushma; Lako, Majlinda.

In: Development, Vol. 146, No. 2, 169474, 15.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - An integrated transcriptional analysis of the developing human retina

AU - Mellough, Carla B.

AU - Bauer, Roman

AU - Collin, Joseph

AU - Dorgau, Birthe

AU - Zerti, Darin

AU - Dolan, David W. P.

AU - Jones, Carl M.

AU - Izuogu, Osagie G.

AU - Yu, Min

AU - Hallam, Dean

AU - Steyn, Jannetta S.

AU - Whites, Kathryn

AU - Steel, David H.

AU - Santibanez-Koref, Mauro

AU - Elliott, David J.

AU - Jackson, Michael S.

AU - Lindsay, Susan

AU - Grellscheid, Sushma

AU - Lako, Majlinda

PY - 2019/1/15

Y1 - 2019/1/15

N2 - The scarcity of embryonic/foetal material as a resource for direct study means that there is still limited understanding of human retina development. Here, we present an integrated transcriptome analysis combined with immunohistochemistry in human eye and retinal samples from 4 to 19 post-conception weeks. This analysis reveals three developmental windows with specific gene expression patterns that informed the sequential emergence of retinal cell types and enabled identification of stage-specific cellular and biological processes, and transcriptional regulators. Each stage is characterised by a specific set of alternatively spliced transcripts that code for proteins involved in the formation of the photoreceptor connecting cilium, pre-mRNA splicing and epigenetic modifiers. Importantly, our data show that the transition from foetal to adult retina is characterised by a large increase in the percentage of mutually exclusive exons that code for proteins involved in photoreceptor maintenance. The circular RNA population is also defined and shown to increase during retinal development. Collectively, these data increase our understanding of human retinal development and the pre-mRNA splicing process, and help to identify new candidate disease genes.

AB - The scarcity of embryonic/foetal material as a resource for direct study means that there is still limited understanding of human retina development. Here, we present an integrated transcriptome analysis combined with immunohistochemistry in human eye and retinal samples from 4 to 19 post-conception weeks. This analysis reveals three developmental windows with specific gene expression patterns that informed the sequential emergence of retinal cell types and enabled identification of stage-specific cellular and biological processes, and transcriptional regulators. Each stage is characterised by a specific set of alternatively spliced transcripts that code for proteins involved in the formation of the photoreceptor connecting cilium, pre-mRNA splicing and epigenetic modifiers. Importantly, our data show that the transition from foetal to adult retina is characterised by a large increase in the percentage of mutually exclusive exons that code for proteins involved in photoreceptor maintenance. The circular RNA population is also defined and shown to increase during retinal development. Collectively, these data increase our understanding of human retinal development and the pre-mRNA splicing process, and help to identify new candidate disease genes.

KW - Developing human retina

KW - Transcriptome

KW - Immunohistochemistry

KW - Alternative splicing

KW - Retinal cells

KW - Circular RNAs

KW - CELL FATE SPECIFICATION

KW - CIRCULAR RNAS

KW - HOMEOBOX GENE

KW - OPTIC-NERVE

KW - HUMAN FOVEA

KW - EXPRESSION

KW - FETAL

KW - EYE

KW - DIFFERENTIATION

KW - PAX6

U2 - 10.1242/dev.169474

DO - 10.1242/dev.169474

M3 - Article

VL - 146

JO - Development

JF - Development

SN - 0950-1991

IS - 2

M1 - 169474

ER -

Mellough CB, Bauer R, Collin J, Dorgau B, Zerti D, Dolan DWP et al. An integrated transcriptional analysis of the developing human retina. Development. 2019 Jan 15;146(2). 169474. https://doi.org/10.1242/dev.169474