Single Cell Heterogeneity is Absent in the Transgenic Paradigm of an Inherited Cataract
48 Pages Posted: 21 Sep 2018More...
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
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