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https://www.readbyqxmd.com/read/29107558/esrp1-mutations-cause-hearing-loss-due-to-defects-in-alternative-splicing-that-disrupt-cochlear-development
#1
Alex M Rohacek, Thomas W Bebee, Richard K Tilton, Caleb M Radens, Chris McDermott-Roe, Natoya Peart, Maninder Kaur, Michael Zaykaner, Benjamin Cieply, Kiran Musunuru, Yoseph Barash, John A Germiller, Ian D Krantz, Russ P Carstens, Douglas J Epstein
Alternative splicing contributes to gene expression dynamics in many tissues, yet its role in auditory development remains unclear. We performed whole-exome sequencing in individuals with sensorineural hearing loss (SNHL) and identified pathogenic mutations in Epithelial Splicing-Regulatory Protein 1 (ESRP1). Patient-derived induced pluripotent stem cells showed alternative splicing defects that were restored upon repair of an ESRP1 mutant allele. To determine how ESRP1 mutations cause hearing loss, we evaluated Esrp1(-/-) mouse embryos and uncovered alterations in cochlear morphogenesis, auditory hair cell differentiation, and cell fate specification...
November 6, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29026781/bulge-region-as-a-putative-hair-follicle-stem-cells-niche-a-brief-review
#2
REVIEW
Sanaz Joulai Veijouye, Abazar Yari, Fatemeh Heidari, Nayereh Sajedi, Fatemeh Ghoroghi Moghani, Maliheh Nobakht
BACKGROUND: Hair follicle stem cells exist in different sites. Most of the hair follicle stem cells are reside in niche called bulge. Bulge region is located between the opening of sebaceous gland and the attachment site of the arrector pili muscle. METHODS: Data were collected using databases and resources of PubMed, Web of Science, Science Direct, Scopus, MEDLINE and their references from the earliest available published to identify English observational studies on hair follicle bulge region...
September 2017: Iranian Journal of Public Health
https://www.readbyqxmd.com/read/28973399/trichothiodystrophy-causative-tfiie%C3%AE-mutation-affects-transcription-in-highly-differentiated-tissue
#3
Arjan F Theil, Imke K Mandemaker, Emile van den Akker, Sigrid M A Swagemakers, Anja Raams, Tatjana Wüst, Jurgen A Marteijn, Jacques C Giltay, Richard M Colombijn, Ute Moog, Urania Kotzaeridou, Mehrnaz Ghazvini, Marieke von Lindern, Jan H J Hoeijmakers, Nicolaas G J Jaspers, Peter J van der Spek, Wim Vermeulen
The rare recessive developmental disorder Trichothiodystrophy (TTD) is characterized by brittle hair and nails. Patients also present a variable set of poorly explained additional clinical features, including ichthyosis, impaired intelligence, developmental delay and anemia. About half of TTD patients are photosensitive due to inherited defects in the DNA repair and transcription factor II H (TFIIH). The pathophysiological contributions of unrepaired DNA lesions and impaired transcription have not been dissected yet...
September 11, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28911317/generation-of-ips-derived-model-cells-for-analyses-of-hair-shaft-differentiation
#4
Takumi Kido, Tomoatsu Horigome, Minori Uda, Naoki Adachi, Yohei Hirai
Biological evaluation of hair growth/differentiation activity in vitro has been a formidable challenge, primarily due to the lack of relevant model cell systems. To solve this problem, we generated a stable model cell line in which successive differentiation via epidermal progenitors to hair components is easily inducible and traceable. Mouse induced pluripotent stem (iPS) cell-derived cells were selected to stably express a tetracycline (Tet)-inducible bone morphogenic protein-4 (BMP4) expression cassette and a luciferase reporter driven by a hair-specific keratin 31 gene (krt31) promoter (Tet-BMP4-KRT31-Luc iPS)...
September 1, 2017: BioTechniques
https://www.readbyqxmd.com/read/28886268/implanted-hair-follicle-associated-pluripotent-hap-stem-cells-encapsulated-in-polyvinylidene-fluoride-membrane-cylinders-promote-effective-recovery-of-peripheral-nerve-injury
#5
Aiko Yamazaki, Kohya Obara, Natsuko Tohgi, Kyoumi Shirai, Sumiyuki Mii, Yuko Hamada, Nobuko Arakawa, Ryoichi Aki, Robert M Hoffman, Yasuyuki Amoh
Hair follicle-associated-pluripotent (HAP) stem cells are located in the bulge area of the hair follicle, express the stem-cell marker, nestin, and have been shown to differentiate to nerve cells, glial cells, keratinocytes, smooth muscle cells, cardiac muscle cells, and melanocytes. Transplanted HAP stem cells promote the recovery of peripheral nerve and spinal cord injuries and have the potential for heart regeneration as well. In the present study, we implanted mouse green fluorescent protein (GFP)-expressing HAP stem-cell spheres encapsulated in polyvinylidene fluoride (PVDF)-membrane cylinders into the severed sciatic nerve of immunocompetent and immunocompromised (nude) mice...
October 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28749199/hair-follicle-associated-pluripotent-hap-stem-cells
#6
Yasuyuki Amoh, Robert M Hoffman
Various types of stem cells reside in the skin, including keratinocyte progenitor cells, melanocyte progenitor cells, skin-derived precursors (SKPs), and nestin-expressing hair follicle-associated-pluripotent (HAP) stem cells. HAP stem cells, located in the bulge area of the hair follicle, have been shown to differentiate to nerve cells, glial cells, keratinocytes, smooth muscle cells, cardiac muscle cells, and melanocytes. HAP stem cells are positive for the stem-cell marker CD34, as well as K15-negative, suggesting their relatively undifferentiated state...
July 27, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28686713/transcriptome-wide-comparison-of-the-impact-of-atoh1-and-mir-183-family-on-pluripotent-stem-cells-and-multipotent-otic-progenitor-cells
#7
COMPARATIVE STUDY
Michael Ebeid, Prashanth Sripal, Jason Pecka, Kirk W Beisel, Kelvin Kwan, Garrett A Soukup
Over 5% of the global population suffers from disabling hearing loss caused by multiple factors including aging, noise exposure, genetic predisposition, or use of ototoxic drugs. Sensorineural hearing loss is often caused by the loss of sensory hair cells (HCs) of the inner ear. A barrier to hearing restoration after HC loss is the limited ability of mammalian auditory HCs to spontaneously regenerate. Understanding the molecular mechanisms orchestrating HC development is expected to facilitate cell replacement therapies...
2017: PloS One
https://www.readbyqxmd.com/read/28643534/transplantation-of-mouse-induced-pluripotent-stem-cells-into-the-cochlea-for-the-treatment-of-sensorineural-hearing-loss
#8
Jing Chen, Lina Guan, Hengtao Zhu, Shan Xiong, Liang Zeng, Hongqun Jiang
CONCLUSION: Mouse-induced pluripotent stem cells (iPSCs) could differentiate into hair cell-like cells and spiral ganglion-like cells after transplantation into mouse cochleae, but it cannot improve the auditory brain response (ABR) thresholds in short term. OBJECTIVE: To evaluate the potential of iPSCs for use as a source of transplants for the treatment of sensorineural hearing loss (SNHL). METHODS: Establishing SNHL mice model, then injecting the iPSCs or equal volume DMEM basic medium into the cochleae, respectively...
June 23, 2017: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/28602615/pten-mediates-activation-of-core-clock-protein-bmal1-and-accumulation-of-epidermal-stem-cells
#9
Chiara Zagni, Luciana O Almeida, Tarek Balan, Marco T Martins, Luciana K Rosselli-Murai, Petros Papagerakis, Rogerio M Castilho, Cristiane H Squarize
Tissue integrity requires constant maintenance of a quiescent, yet responsive, population of stem cells. In the skin, hair follicle stem cells (HFSCs) that reside within the bulge maintain tissue homeostasis in response to activating cues that occur with each new hair cycle or upon injury. We found that PTEN, a major regulator of the PI3K-AKT pathway, controlled HFSC number and size in the bulge and maintained genomically stable pluripotent cells. This regulatory function is central for HFSC quiescence, where PTEN-deficiency phenotype is in part regulated by BMAL1...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28592171/next-generation-human-skin-constructs-as-advanced-tools-for-drug-development
#10
REVIEW
H E Abaci, Zongyou Guo, Yanne Doucet, Joanna Jacków, Angela Christiano
Many diseases, as well as side effects of drugs, manifest themselves through skin symptoms. Skin is a complex tissue that hosts various specialized cell types and performs many roles including physical barrier, immune and sensory functions. Therefore, modeling skin in vitro presents technical challenges for tissue engineering. Since the first attempts at engineering human epidermis in 1970s, there has been a growing interest in generating full-thickness skin constructs mimicking physiological functions by incorporating various skin components, such as vasculature and melanocytes for pigmentation...
November 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28565767/hair-follicle-derived-mesenchymal-cells-support-undifferentiated-growth-of-embryonic-stem-cells
#11
Vanessa Carvalho Coelho de Oliveira, Danúbia Silva Dos Santos, Leandro Vairo, Tais Hanae Kasai Brunswick, Luiz Alberto Soares Pimentel, Adriana Bastos Carvalho, Antonio Carlos Campos de Carvalho, Regina Coeli Dos Santos Goldenberg
The aim of the present study was to investigate whether feeder layers composed of human hair follicle-derived mesenchymal stem cells (hHFDCs) are able to support human embryonic stem cells (hESCs). hHFDCs and mouse embryonic fibroblasts (MEFs) were isolated and cultured in Dulbecco's modified Eagle's medium (DMEM)/F-12 and low-glucose DMEM, respectively. hHFDCs were passaged three times and subsequently characterized. hHFDCs and MEFs were mitotically inactivated with mitomycin C for 3 h prior to co-culture with H9-hESCs...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28534946/differentiation-of-nestin%C3%A2-negative-human-hair-follicle-outer-root-sheath-cells-into-neurons-in%C3%A2-vitro
#12
Wei Wu, Xiao-Li Wu, Yu-Qing Ji, Zhen Gao
A specialized quiescent population of hair follicle stem cells, residing in the hair follicle outer root sheath cells (ORSCs), has previously demonstrated pluripotency for differentiation into neural stem cells (NSCs). A previous study indicated that nestin‑positive hair follicle ORSCs are able to differentiate into neurons. However, little has been reported on the isolation of nestin‑negative human ORSCs and whether they can successfully differentiate into neurons in vitro. In the present study, nestin‑positive ORSCs were significantly reduced with a prolonged incubation time in vitro...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28459451/generation-of-inner-ear-organoids-containing-functional-hair-cells-from-human-pluripotent-stem-cells
#13
Karl R Koehler, Jing Nie, Emma Longworth-Mills, Xiao-Ping Liu, Jiyoon Lee, Jeffrey R Holt, Eri Hashino
The derivation of human inner ear tissue from pluripotent stem cells would enable in vitro screening of drug candidates for the treatment of hearing and balance dysfunction and may provide a source of cells for cell-based therapies of the inner ear. Here we report a method for differentiating human pluripotent stem cells to inner ear organoids that harbor functional hair cells. Using a three-dimensional culture system, we modulate TGF, BMP, FGF, and WNT signaling to generate multiple otic-vesicle-like structures from a single stem-cell aggregate...
June 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28387239/survival-of-human-embryonic-stem-cells-implanted-in-the-guinea-pig-auditory-epithelium
#14
Min Young Lee, Sandra Hackelberg, Kari L Green, Kelly G Lunghamer, Takaomi Kurioka, Benjamin R Loomis, Donald L Swiderski, R Keith Duncan, Yehoash Raphael
Hair cells in the mature cochlea cannot spontaneously regenerate. One potential approach for restoring hair cells is stem cell therapy. However, when cells are transplanted into scala media (SM) of the cochlea, they promptly die due to the high potassium concentration. We previously described a method for conditioning the SM to make it more hospitable to implanted cells and showed that HeLa cells could survive for up to a week using this method. Here, we evaluated the survival of human embryonic stem cells (hESC) constitutively expressing GFP (H9 Cre-LoxP) in deaf guinea pig cochleae that were pre-conditioned to reduce potassium levels...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345660/zinc-deficiency-and-low-enterocyte-zinc-transporter-expression-in-human-patients-with-autism-related-mutations-in-shank3
#15
Stefanie Pfaender, Ann Katrin Sauer, Simone Hagmeyer, Katharina Mangus, Leonhard Linta, Stefan Liebau, Juergen Bockmann, Guillaume Huguet, Thomas Bourgeron, Tobias M Boeckers, Andreas M Grabrucker
Phelan McDermid Syndrome (PMDS) is a genetic disorder characterized by features of Autism spectrum disorders. Similar to reports of Zn deficiency in autistic children, we have previously reported high incidence of Zn deficiency in PMDS. However, the underlying mechanisms are currently not well understood. Here, using inductively coupled plasma mass-spectrometry to measure the concentration of Zinc (Zn) and Copper (Cu) in hair samples from individuals with PMDS with 22q13.3 deletion including SHANK3 (SH3 and multiple ankyrin repeat domains 3), we report a high rate of abnormally low Zn/Cu ratios...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220862/induction-of-hair-follicle-dermal-papilla-cell-properties-in-human-induced-pluripotent-stem-cell-derived-multipotent-lngfr-thy-1-mesenchymal-cells
#16
Ophelia Veraitch, Yo Mabuchi, Yumi Matsuzaki, Takashi Sasaki, Hironobu Okuno, Aki Tsukashima, Masayuki Amagai, Hideyuki Okano, Manabu Ohyama
The dermal papilla (DP) is a specialised mesenchymal component of the hair follicle (HF) that plays key roles in HF morphogenesis and regeneration. Current technical difficulties in preparing trichogenic human DP cells could be overcome by the use of highly proliferative and plastic human induced pluripotent stem cells (hiPSCs). In this study, hiPSCs were differentiated into induced mesenchymal cells (iMCs) with a bone marrow stromal cell phenotype. A highly proliferative and plastic LNGFR(+)THY-1(+) subset of iMCs was subsequently programmed using retinoic acid and DP cell activating culture medium to acquire DP properties...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28192743/behavior-of-leucine-rich-repeat-containing-g-protein-coupled-receptor-5-expressing-cells-in-the-reprogramming-process
#17
Yuko Arioka, Hiroyasu Ito, Akihiro Hirata, Katsunori Semi, Yasuhiro Yamada, Mitsuru Seishima
It remains unclear what cells are proper for the generation of induced pluripotent stem cells (iPSCs). Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is well known as a tissue stem cell and progenitor marker, both of which are reported to be sensitive to reprogramming. In the present study, we examined the reprogramming behavior of Lgr5-expressing cells (Lgr5+ cells). First, we compared reprogramming behavior using mouse Lgr5+ and Lgr5 negative (Lgr5-) hair follicles (HFs). The number of alkaline phosphatase staining-positive cells was lesser in a well of Lgr5+ HFs than in Lgr5- HFs; however, the ratio of Nanog+ SSEA1+ cells in the cell mixture derived from Lgr5+ HFs was much higher than that from Lgr5- HFs...
April 2017: Stem Cell Research
https://www.readbyqxmd.com/read/27966334/study-of-mouse-induced-pluripotent-stem-cell-transplantation-intowistar-albino-rat-cochleae-after-hair-cell-damage
#18
Mustafa Kürşat Gökcan, Selçuk Mülazimoğlu, Emre Ocak, Pınar Can, Murat Çalışkan, Ömer Beşaltı, Serpil Dizbay Sak, Gülşah Kaygusuz
BACKGROUND/AIM: As the regeneration capacity of hair cells is limited, inner ear stem cell therapies hold promise. Effects of mouse induced pluripotent stem cells (IPSCs) on Wistar albino rats (WARs) with hearing impairment were investigated. MATERIALS AND METHODS: Thirty-five adult WARs with normal hearing were divided into 4 groups. Excluding the study group (n = 15), the other three groups served as control groups for ototoxicity and IPSC injection models. IPSC injections were performed via cochleostomy after a retroauricular approach...
November 17, 2016: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/27880068/human-hair-follicle-associated-pluripotent-hhap-stem-cells-differentiate-to-cardiac-muscle-cells
#19
Natsuko Tohgi, Koya Obara, Masateru Yashiro, Yuko Hamada, Nobuko Arakawa, Sumiyuki Mii, Ryoichi Aki, Robert M Hoffman, Yasuyuki Amoh
We have previously demonstrated that nestin-expressing hair follicle-associated-pluripotent (HAP) stem cells are located in the bulge area. HAP stem cells have been previously shown to differentiate to neurons, glial cells, keratinocytes, smooth-muscle cells, melanocytes and cardiac-muscle cells in vitro. Subsequently, we demonstrated that HAP stem cells could effect nerve and spinal cord regeneration in mouse models, differentiating to Schwann cells and neurons. In previous studies, we established an efficient protocol for the differentiation of cardiac-muscle cells from mouse HAP stem cells...
January 2, 2017: Cell Cycle
https://www.readbyqxmd.com/read/27867768/induced-pluripotent-stem-cells-from-human-hair-follicle-keratinocytes-as-a-potential-source-for-in-vitro-hair-follicle-cloning
#20
Sheng Jye Lim, Shu Cheow Ho, Pooi Ling Mok, Kian Lee Tan, Alan H K Ong, Seng Chiew Gan
BACKGROUND: Human hair follicles are important for the renewal of new hairs and their development. The generation of induced pluripotent stem cells (iPSCs) from hair follicles is easy due to its accessibility and availability. The pluripotent cells derived from hair follicles not only have a higher tendency to re-differentiate into hair follicles, but are also more suited for growth in hair scalp tissue microenvironment. METHODS: In this study, human hair follicular keratinocytes were used to generate iPSCs, which were then further differentiated in vitro into keratinocytes...
2016: PeerJ
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