Thyroid hormone signaling specifies cone subtypes in human retinal organoids

Kiara C. Eldred; Sarah E. Hadyniak; Katarzyna A. Hussey; Boris Brenerman; Ping Wu Zhang; Xitiz Chamling; Valentin M. Sluch; Derek S. Welsbie; Samer Hattar; James Taylor; Karl Wahlin; Donald J. Zack; Robert J. Johnston

doi:10.1126/science.aau6348

Thyroid hormone signaling specifies cone subtypes in human retinal organoids

Kiara C. Eldred, Sarah E. Hadyniak, Katarzyna A. Hussey, Boris Brenerman, Ping Wu Zhang, Xitiz Chamling, Valentin M. Sluch, Derek S. Welsbie, Samer Hattar, James Taylor, Karl Wahlin, Donald J. Zack, Robert J. Johnston

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Abstract

The mechanisms underlying specification of neuronal subtypes within the human nervous system are largely unknown. The blue (S), green (M), and red (L) cones of the retina enable high-acuity daytime and color vision.To determine the mechanism that controls S versus L/M fates, we studied the differentiation of human retinal organoids. Organoids and retinas have similar distributions, expression profiles, and morphologies of cone subtypes. S cones are specified first, followed by L/M cones, and thyroid hormone signaling controls this temporal switch. Dynamic expression of thyroid hormone-degrading and-activating proteins within the retina ensures low signaling early to specify S cones and high signaling late to produce L/M cones. This work establishes organoids as a model for determining mechanisms of human development with promising utility for therapeutics and vision repair.

Original language	English (US)
Article number	eaau6348
Journal	Science
Volume	362
Issue number	6411
DOIs	https://doi.org/10.1126/science.aau6348
State	Published - Oct 12 2018

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title = "Thyroid hormone signaling specifies cone subtypes in human retinal organoids",

abstract = "The mechanisms underlying specification of neuronal subtypes within the human nervous system are largely unknown. The blue (S), green (M), and red (L) cones of the retina enable high-acuity daytime and color vision.To determine the mechanism that controls S versus L/M fates, we studied the differentiation of human retinal organoids. Organoids and retinas have similar distributions, expression profiles, and morphologies of cone subtypes. S cones are specified first, followed by L/M cones, and thyroid hormone signaling controls this temporal switch. Dynamic expression of thyroid hormone-degrading and-activating proteins within the retina ensures low signaling early to specify S cones and high signaling late to produce L/M cones. This work establishes organoids as a model for determining mechanisms of human development with promising utility for therapeutics and vision repair.",

author = "Eldred, {Kiara C.} and Hadyniak, {Sarah E.} and Hussey, {Katarzyna A.} and Boris Brenerman and Zhang, {Ping Wu} and Xitiz Chamling and Sluch, {Valentin M.} and Welsbie, {Derek S.} and Samer Hattar and James Taylor and Karl Wahlin and Zack, {Donald J.} and Johnston, {Robert J.}",

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doi = "10.1126/science.aau6348",

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AU - Eldred, Kiara C.

AU - Hadyniak, Sarah E.

AU - Hussey, Katarzyna A.

AU - Brenerman, Boris

AU - Zhang, Ping Wu

AU - Chamling, Xitiz

AU - Sluch, Valentin M.

AU - Welsbie, Derek S.

AU - Hattar, Samer

AU - Taylor, James

AU - Wahlin, Karl

AU - Zack, Donald J.

AU - Johnston, Robert J.

PY - 2018/10/12

Y1 - 2018/10/12

N2 - The mechanisms underlying specification of neuronal subtypes within the human nervous system are largely unknown. The blue (S), green (M), and red (L) cones of the retina enable high-acuity daytime and color vision.To determine the mechanism that controls S versus L/M fates, we studied the differentiation of human retinal organoids. Organoids and retinas have similar distributions, expression profiles, and morphologies of cone subtypes. S cones are specified first, followed by L/M cones, and thyroid hormone signaling controls this temporal switch. Dynamic expression of thyroid hormone-degrading and-activating proteins within the retina ensures low signaling early to specify S cones and high signaling late to produce L/M cones. This work establishes organoids as a model for determining mechanisms of human development with promising utility for therapeutics and vision repair.

AB - The mechanisms underlying specification of neuronal subtypes within the human nervous system are largely unknown. The blue (S), green (M), and red (L) cones of the retina enable high-acuity daytime and color vision.To determine the mechanism that controls S versus L/M fates, we studied the differentiation of human retinal organoids. Organoids and retinas have similar distributions, expression profiles, and morphologies of cone subtypes. S cones are specified first, followed by L/M cones, and thyroid hormone signaling controls this temporal switch. Dynamic expression of thyroid hormone-degrading and-activating proteins within the retina ensures low signaling early to specify S cones and high signaling late to produce L/M cones. This work establishes organoids as a model for determining mechanisms of human development with promising utility for therapeutics and vision repair.

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Thyroid hormone signaling specifies cone subtypes in human retinal organoids

Abstract

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