scholarly journals Stepwise Induction of Inner Ear Hair Cells From Mouse Embryonic Fibroblasts via Mesenchymal- to-Epithelial Transition and Formation of Otic Epithelial Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Qiong Yang ◽  
Haosong Shi ◽  
Yizhou Quan ◽  
Qianqian Chen ◽  
Wang Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Inner Ear ◽  
Hair Cells ◽  
Embryonic Stem ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Mesenchymal To Epithelial Transition ◽  
Specific Proteins ◽  
Induced Pluripotent

Although embryonic stem cells or induced pluripotent stem cells are able to differentiate into inner ear hair cells (HCs), they have drawbacks limiting their clinical application, including a potential risk of tumourigenicity. Direct reprogramming of fibroblasts to inner ear HCs could offer an alternative solution to this problem. Here, we present a stepwise guidance protocol to induce mouse embryonic fibroblasts to differentiate into inner ear HC-like cells (HCLs) via mesenchymal-to-epithelial transition and then acquisition of otic sensory epithelial cell traits by overexpression of three key transcription factors. These induced HCLs express multiple HC-specific proteins, display protrusions reminiscent of ciliary bundle structures, respond to voltage stimulation, form functional mechanotransduction channels, and exhibit a transcriptional profile of HC signature. Together, our work provides a new method to produce functional HCLs in vitro, which may have important implications for studies of HC development, drug discovery, and cell replacement therapy for hearing loss.

scholarly journals Dysfunction telomeres in embryonic fibroblasts and cultured in vitro pluripotent stem cells of Rattus norvegicus (Rodentia, Muridae)

2019 ◽  
Vol 13 (3) ◽  
pp. 197-210
Author(s):  
Natalya S. Zhdanova ◽  
Evgenia A. Vaskova ◽  
Tatyana V. Karamysheva ◽  
Julia M. Minina ◽  
Nicolay Rubtsov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Lines ◽  
Pluripotent Stem Cells ◽  
Rattus Norvegicus ◽  
Embryonic Stem ◽  
Telomere Dysfunction ◽  
Embryonic Fibroblasts ◽  
Damage Response ◽  
Induced Pluripotent

We studied the level of spontaneous telomere dysfunction in Rattus norvegicus (Berkenhout, 1769) (Rodentia, Muridae) embryonic fibroblasts (rEFs) and in cultured in vitro rat pluripotent stem cells (rPSCs), embryonic stem cells (rESCs) and induced pluripotent stem cells (riPSCs), on early passages and after prolonged cultivation. Among studied cell lines, rESCs showed the lowest level of telomere dysfunction, while the riPSCs demonstrated an elevated level on early passages of cultivation. In cultivation, the frequency of dysfunctional telomeres has increased in all studied cell lines; this is particularly true for dysfunctional telomeres occurring in G1 stage in riPSCs. The obtained data are mainly discussed in the connection with the specific structure of the telomere regions and their influence on the differential DNA damage response in them.

Mini Review; Differentiation of Human Pluripotent Stem Cells into Oocytes

2020 ◽  
Vol 15 (4) ◽  
pp. 301-307 ◽  
Author(s):  
Gaifang Wang ◽  
Maryam Farzaneh
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Human Pluripotent Stem Cells ◽  
Human Oocyte ◽  
Differentiation Potential ◽  
Cell Lineages ◽  
Cell Based Therapy ◽  
Induced Pluripotent

Primary Ovarian Insufficiency (POI) is one of the main diseases causing female infertility that occurs in about 1% of women between 30-40 years of age. There are few effective methods for the treatment of women with POI. In the past few years, stem cell-based therapy as one of the most highly investigated new therapies has emerged as a promising strategy for the treatment of POI. Human pluripotent stem cells (hPSCs) can self-renew indefinitely and differentiate into any type of cell. Human Embryonic Stem Cells (hESCs) as a type of pluripotent stem cells are the most powerful candidate for the treatment of POI. Human-induced Pluripotent Stem Cells (hiPSCs) are derived from adult somatic cells by the treatment with exogenous defined factors to create an embryonic-like pluripotent state. Both hiPSCs and hESCs can proliferate and give rise to ectodermal, mesodermal, endodermal, and germ cell lineages. After ovarian stimulation, the number of available oocytes is limited and the yield of total oocytes with high quality is low. Therefore, a robust and reproducible in-vitro culture system that supports the differentiation of human oocytes from PSCs is necessary. Very few studies have focused on the derivation of oocyte-like cells from hiPSCs and the details of hPSCs differentiation into oocytes have not been fully investigated. Therefore, in this review, we focus on the differentiation potential of hPSCs into human oocyte-like cells.

scholarly journals Differences between Cellular and Molecular Profiles of Induced Pluripotent Stem Cells Generated from Mouse Embryonic Fibroblasts

2010 ◽  
Vol 12 (6) ◽  
pp. 627-639 ◽  
Author(s):  
Eun Young Kim ◽  
Kilsoo Jeon ◽  
Hyo Young Park ◽  
Young Joon Han ◽  
Byoung Chul Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Molecular Profiles ◽  
Induced Pluripotent

scholarly journals Bone marrow mesenchymal stem cells are progenitors in vitro for inner ear hair cells

2007 ◽  
Vol 34 (1) ◽  
pp. 59-68 ◽  
Author(s):  
Sang-Jun Jeon ◽  
Kazuo Oshima ◽  
Stefan Heller ◽  
Albert S.B. Edge
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Inner Ear ◽  
Hair Cells ◽  
Marrow Mesenchymal Stem Cells

scholarly journals Ethanol Inactivated Mouse Embryonic Fibroblasts Maintain the Self-Renew and Proliferation of Human Embryonic Stem Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0130332 ◽  
Author(s):  
Boxian Huang ◽  
Song Ning ◽  
Lili Zhuang ◽  
Chunyan Jiang ◽  
Yugui Cui ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
The Self ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts

scholarly journals Establishment and Identification of a CiPSC Lineage Reprogrammed from FSP-tdTomato Mouse Embryonic Fibroblasts (MEFs)

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ruiping Chen ◽  
Wenxiu Xie ◽  
Baomei Cai ◽  
Yue Qin ◽  
Chuman Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Small Molecule ◽  
Fluorescent Protein ◽  
Day Treatment ◽  
Tracking System ◽  
Embryonic Stem ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Underlying Mechanisms

Safety issues associated with transcription factors or viruses may be avoided with the use of chemically induced pluripotent stem cells (CiPSCs), thus promoting their clinical application. Previously, we had successfully developed and standardized an induction method using small-molecule compound, with simple operation, uniform induction conditions, and clear constituents. In order to verify that the CiPSCs were indeed reprogrammed from mouse embryonic fibroblasts (MEFs), and further explore the underlying mechanisms, FSP-tdTomato mice were used to construct a fluorescent protein-tracking system of MEFs, for revealing the process of CiPSC reprogramming. CiPSCs were identified by morphological analysis, mRNA, and protein expression of pluripotency genes, as well as teratoma formation experiments. Results showed that after 40-day treatment of tdTomato-MEFs with small-molecule compounds, the cells were presented with prominent nucleoli, high core-to-cytoplasmic ratio, round shape, group and mass arrangement, and high expression of pluripotency gene. These cells could differentiate into three germ layer tissues in vivo. As indicated by the above results, tdTomato-MEFs could be reprogrammed into CiPSCs, a lineage that possesses pluripotency similar to mouse embryonic stem cells (mESCs), with the use of small-molecule compounds. The establishment of CiPSC lineage, tracked by fluorescent protein, would benefit further studies exploring its underlying mechanisms. With continuous expression of fluorescent proteins during cellular differentiation, this cell lineage could be used for tracking CiPSC transplantation and differentiation into functional cells.

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