Abstract
This study was conducted to determine the dynamic Islet1 and Brn3 (POU4F) expression pattern in the human fetal retina and human-induced pluripotent stem cell- (hiPSC-) derived retinal organoid. Human fetal eyes from 8 to 27 fetal weeks (Fwks), human adult retina, hiPSC-derived retinal organoid from 7 to 31 differentiation weeks (Dwks), and rhesus adult retina were collected for cyrosectioning. Immunofluorescence analysis showed that Islet1 was expressed in retinal ganglion cells in the fetal retina, human adult retina, and retinal organoids. Unexpectedly, after Fwk 20, Brn3 expression gradually decreased in the fetal retina. In the midstage of development, Islet1 was detected in bipolar and developing horizontal cells. As the photoreceptor developed, the Islet1-positive cone precursors gradually became Islet1-negative/S-opsin-positive cones. This study highlights the distinguishing characteristics of Islet1 dynamic expression in human fetal retina development and proposes more concerns which should be taken regarding Brn3 as a cell-identifying marker in mature primate retina.
Highlights
Islet1, known as ISL1, is a LIM-homeodomain transcription factor that plays critical roles in differentiation, cell specification, and phenotype maintenance of horizontal cells as well as cholinergic amacrine and ganglion cells in the retina of different species including fish, reptiles, birds, amphibians, chickens, and mammals
We evaluated the dynamic expression of Islet1 in the human fetal retina and compared the human-induced pluripotent stem cell- (hiPSC-)derived retinal organoid with human fetal retina development
We found the Islet1 was expressed in cone precursors of the human fetal retina
Summary
Known as ISL1, is a LIM-homeodomain transcription factor that plays critical roles in differentiation, cell specification, and phenotype maintenance of horizontal cells as well as cholinergic amacrine and ganglion cells in the retina of different species including fish, reptiles, birds, amphibians, chickens, and mammals. Numerous studies have revealed that ISL1 plays a key role in multiple tissue types, such as the heart [1], kidneys [2], skeletal muscle, endocrine organs [3], and nervous system [4]. ISL1, as a crucial transcription factor, is required for retinal neuroblast differentiation during human retinogenesis. Various previous studies demonstrated Islet dynamic expression shows a specific temporal and spatial pattern in the retina of multiple animal models [6,7,8,9,10]. The detailed Islet expression pattern during human retinal development remains unclear
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