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Single Cell Heterogeneity is Absent in the Transgenic Paradigm of an Inherited Cataract

48 Pages Posted: 21 Sep 2018

See all articles by Suraj Bhat

Suraj Bhat

University of California, Los Angeles (UCLA) - Stein Eye Institute; University of California, Los Angeles (UCLA) - Brain Research Institute; University of California, Los Angeles (UCLA) - Molecular Biology Institute

Rajendra K. Gangalum

University of California, Los Angeles (UCLA) - Stein Eye Institute

Dongjae Kim

University of California, Los Angeles (UCLA) - Stein Eye Institute

Serghei Mangul

University of California, Los Angeles (UCLA) - Department of Computer Science and Human Genetics

Raj K. Kashyap

University of California, Los Angeles (UCLA) - Stein Eye Institute

Zhou Xinxai

University of California, Los Angeles (UCLA) - Department of Medicine

David Elashoff

University of California, Los Angeles (UCLA) - Department of Medicine

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Abstract

We have shown recently that highly variable transcriptional activity in single cortical fiber cells mediates the transition from nascent to terminally differentiated fiber cells in the developing ocular lens. The lens is composed of only two cell types, the anterior epithelium and the fiber cells derived from it; the fiber cell morphogenesis proceeds in an order that positions terminally differentiated oldest fiber cells in the center and the youngest nascent fiber cells, entering differentiation, at the periphery of the lens. This pattern of growth produces layers of cells, which when isolated as single cells retain their molecular and spatial context. Here, working with an inherited cataract paradigm, we demonstrate a remarkable absence of transcriptional heterogeneity concomitant with the absence of terminal differentiation. The spatial context of the data, obtained from single isolated fiber cells suggests that homogenization of gene activity may be a prelude to impending pathology when a mutation disrupts development.

Funding: This work was supported the Gerald Oppenheimer Family Foundation for the Prevention of Eye Disease Endowment Fund and by the NIH grant (1R01EY024929) to SPB.

Declaration of Interest: Authors declare no competing interests.

Ethical Approval: All the work with animals followed the institutional guidelines and protocols approved by Animal Research Committee (UCLA).

Keywords: Spatial transcriptomics; single cells; developmental mutation; heterogeneity of gene expression and disease; inherited cataract; differentiation; molecular progression; molecular identity; crystallins; ocular lens

Suggested Citation

Bhat, Suraj and Gangalum, Rajendra K. and Kim, Dongjae and Mangul, Serghei and Kashyap, Raj K. and Xinxai, Zhou and Elashoff, David, Single Cell Heterogeneity is Absent in the Transgenic Paradigm of an Inherited Cataract (January 9, 2018). Available at SSRN: https://ssrn.com/abstract=3244893

Suraj Bhat (Contact Author)

University of California, Los Angeles (UCLA) - Stein Eye Institute ( email )

405 Hilgard Avenue
Box 951361
Los Angeles, CA 90095
United States

University of California, Los Angeles (UCLA) - Brain Research Institute

Box 951761
Los Angeles, CA 90095-1761
United States

University of California, Los Angeles (UCLA) - Molecular Biology Institute

405 Hilgard Avenue
Box 951361
Los Angeles, CA 90095
United States

Rajendra K. Gangalum

University of California, Los Angeles (UCLA) - Stein Eye Institute

405 Hilgard Avenue
Box 951361
Los Angeles, CA 90095
United States

Dongjae Kim

University of California, Los Angeles (UCLA) - Stein Eye Institute

405 Hilgard Avenue
Box 951361
Los Angeles, CA 90095
United States

Serghei Mangul

University of California, Los Angeles (UCLA) - Department of Computer Science and Human Genetics

405 Hilgard Avenue
Box 951361
Los Angeles, CA 90095
United States

Raj K. Kashyap

University of California, Los Angeles (UCLA) - Stein Eye Institute

405 Hilgard Avenue
Box 951361
Los Angeles, CA 90095
United States

Zhou Xinxai

University of California, Los Angeles (UCLA) - Department of Medicine

Los Angeles, CA
United States

David Elashoff

University of California, Los Angeles (UCLA) - Department of Medicine

Los Angeles, CA
United States

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