Quantification of Retinogenesis in 3D Cultures Reveals Epigenetic Memory and Higher Efficiency in iPSCs Derived from Rod Photoreceptors.

Cell Stem Cell

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN 38163, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address:

Published: July 2015

AI Article Synopsis

  • Research on cell-based therapies for retinal degeneration is ongoing, and the importance of stem cell source for creating transplantable differentiated cells is under investigation.
  • Induced pluripotent stem cells derived from murine rod photoreceptors (r-iPSCs) demonstrated greater efficiency in creating retinae compared to embryonic stem cells (ESCs) and fibroblast-derived iPSCs (f-iPSCs).
  • Findings reveal that DNA methylation impacts deficiencies in f-iPSC-derived retinae and highlight the role of rod-specific CTCF binding sites in promoting r-iPSC retinogenesis, emphasizing the significance of stem cell origin in generating retinal neurons in 3D organ cultures.

Article Abstract

Cell-based therapies to treat retinal degeneration are now being tested in clinical trials. However, it is not known whether the source of stem cells is important for the production of differentiated cells suitable for transplantation. To test this, we generated induced pluripotent stem cells (iPSCs) from murine rod photoreceptors (r-iPSCs) and scored their ability to make retinae by using a standardized quantitative protocol called STEM-RET. We discovered that r-iPSCs more efficiently produced differentiated retinae than did embryonic stem cells (ESCs) or fibroblast-derived iPSCs (f-iPSCs). Retinae derived from f-iPSCs had fewer amacrine cells and other inner nuclear layer cells. Integrated epigenetic analysis showed that DNA methylation contributes to the defects in f-iPSC retinogenesis and that rod-specific CTCF insulator protein-binding sites may promote r-iPSC retinogenesis. Together, our data suggest that the source of stem cells is important for producing retinal neurons in three-dimensional (3D) organ cultures.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4547539PMC
http://dx.doi.org/10.1016/j.stem.2015.05.015DOI Listing

Publication Analysis

Top Keywords

stem cells
16
rod photoreceptors
8
source stem
8
cells
7
quantification retinogenesis
4
retinogenesis cultures
4
cultures reveals
4
reveals epigenetic
4
epigenetic memory
4
memory higher
4

Similar Publications

Chitosan-based injectable porous microcarriers with enhanced adipogenic differentiation and angiogenesis for subcutaneous adipose tissue regeneration.

Biomater Adv

January 2025

Key Laboratory of Theoretical Organic Chemistry and Functional Molecule of the Ministry of Education, Hunan Provincial Key Laboratory of Controllable Preparation and Functional Application of Fine Polymers, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, PR China. Electronic address:

Chitosan is a promising biomaterial for tissue engineering, but its functionality is limited by a lack of bioactive sites. This study develops chitosan/amniotic membrane microcarriers to enhance vascularization and tissue regeneration for subcutaneous adipose tissue. The incorporation of decellularized amniotic membrane enhances the bioactivities of chitosan in promoting cell differentiation and angiogenesis.

View Article and Find Full Text PDF

An updated systematic review about various effects of microplastics on cancer: A pharmacological and in-silico based analysis.

Mol Aspects Med

January 2025

Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Epidemiology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan; Department of Natural Sciences, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan. Electronic address:

Microplastics (MPs) are known as substantial environmental and health threats because of their pervasive existence and potential function in human diseases. This study is the first research in which a comprehensive analysis of various impacts of MPs on cancer cells is performed through pharmacological and in silico approaches. Moreover, our results demonstrate that MPs have both promotive and suppressive impacts on cancer cells, changing some of the important features of these kinds of cells including cellular viability, migration, metastasis, and apoptosis.

View Article and Find Full Text PDF

Fate erasure logic of gene networks underlying direct neuronal conversion of somatic cells by microRNAs.

Cell Rep

January 2025

Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address:

Neurogenic microRNAs 9/9 and 124 (miR-9/9-124) drive the direct reprogramming of human fibroblasts into neurons with the initiation of the fate erasure of fibroblasts. However, whether the miR-9/9-124 fate erasure logic extends to the neuronal conversion of other somatic cell types remains unknown. Here, we uncover that miR-9/9-124 induces neuronal conversion of multiple cell types: dura fibroblasts, astrocytes, smooth muscle cells, and pericytes.

View Article and Find Full Text PDF

A common digestive system cancer with a dismal prognosis and a high death rate globally is breast cancer (BRCA). BRCA recurrence, metastasis, and medication resistance are all significantly impacted by cancer stem cells (CSCs). However, the relationship between CSCs and the tumor microenvironment in BRCA individuals remains unknown, and this information is critically needed.

View Article and Find Full Text PDF

Background Aims: Extracellular vesicles (EVs) have gained traction as potential cell-free therapeutic candidates. Development of purification methods that are scalable and robust is a major focus of EV research. Yet there is still little in the literature that evaluates purification methods against potency of the EV product.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!