Stem Cell Reports
Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; Department of Developmental Biology, Washington University in St. Louis, St. Louis, MO 63110, USA; Center of Regenerative Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA. Electronic address:
Published: August 2017
Dyskeratosis congenita (DC) is a bone marrow failure syndrome associated with telomere dysfunction. The progression and molecular determinants of hematopoietic failure in DC remain poorly understood. Here, we use the directed differentiation of human embryonic stem cells harboring clinically relevant mutations in telomerase to understand the consequences of DC-associated mutations on the primitive and definitive hematopoietic programs. Interestingly, telomere shortening does not broadly impair hematopoiesis, as primitive hematopoiesis is not impaired in DC cells. In contrast, while phenotypic definitive hemogenic endothelium is specified, the endothelial-to-hematopoietic transition is impaired in cells with shortened telomeres. This failure is caused by DNA damage accrual and is mediated by p53 stabilization. These observations indicate that detrimental effects of telomere shortening in the hematopoietic system are specific to the definitive hematopoietic lineages. This work illustrates how telomere dysfunction impairs hematopoietic development and creates a robust platform for therapeutic discovery for treatment of DC patients.
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http://dx.doi.org/10.1016/j.stemcr.2017.06.015 | DOI Listing |
J Med Case Rep
January 2025
Department of Hepatic Biliary Pancreatic Medicine, First Hospital of Jilin University, 1 Xinmin Avenue, Changchun, 130021, China.
Background: Dyskeratosis congenita is a rare genetic disease due to telomere biology disorder and characterized by heterogeneous clinical manifestations and severe complications. "Porto-sinusoidal vascular disease" has been recently proposed, according to new diagnostic criteria, to replace the term "idiopathic non-cirrhotic portal hypertension." TERT plays an important role in telomeric DNA repair and replication.
View Article and Find Full Text PDFAndes Pediatr
October 2024
Facultad de Ciencias de la Salud, Universidad Icesi, Cali, Colombia.
Unlabelled: Inherited Bone Marrow Failure syndromes account for approximately 25% of cases of aplastic anemia in pediatric patients. Next-generation sequencing (NGS) technologies have allowed the diagnosis of an increasing number of hereditary causes of bone marrow failure.
Objective: To determine the diagnostic yield and clinical concordance of NGS in the diagnosis of a cohort of pediatric patients with bone marrow failure.
Int J Ophthalmol
December 2024
Department of Ophthalmology, the Affiliated Hospital of Yunnan University, Kunming 650000, Yunnan Province, China.
JMIR Form Res
December 2024
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.
Background: Web-based information and social support are commonly used in rare disease communities where geographic dispersion and limited provider expertise complicate in-person support. We examined web-based resource use among caregivers of individuals with telomere biology disorders (TBDs), which are rare genetic conditions with long diagnostic odysseys and uncertain prognoses including multiorgan system cancer risk.
Objective: This study explored internet-based information-seeking and social support practices and perspectives of patients with TBDs and their caregivers.
Ann Med Surg (Lond)
December 2024
University of Health Sciences, Adana Faculty of Medicine, Adana City Education and Research Hospital, Department of Pediatric Hematology and Oncology, Adana, Turkey.
Introduction And Importance: Dyskeratosis congenita (DC) is a rare multisystem disorder primarily characterized by bone marrow failure due to telomere shortening. Typical clinical features include oral leukoplakia, skin hyperpigmentation, and nail dystrophy, along with an increased risk of malignancies. Hoyeraal-Hreidarsson syndrome (HH), a severe variant of DC, is associated with profound neurological and immunological complications, emphasizing the importance of early diagnosis and genetic evaluation to guide appropriate management.
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