Epigenetics plays critical roles in controlling stem cell self-renewal and differentiation. Histone H1 is one of the most critical chromatin regulators, but its role in adult stem cell regulation remains unclear. Here we report that H1 is intrinsically required in the regulation of germline stem cells (GSCs) in the Drosophila ovary. The loss of H1 from GSCs causes their premature differentiation through activation of the key GSC differentiation factor bam. Interestingly, the acetylated H4 lysine 16 (H4K16ac) is selectively augmented in the H1-depleted GSCs. Furthermore, overexpression of mof reduces H1 association on chromatin. In contrast, the knocking down of mof significantly rescues the GSC loss phenotype. Taken together, these results suggest that H1 functions intrinsically to promote GSC self-renewal by antagonizing MOF function. Since H1 and H4K16 acetylation are highly conserved from fly to human, the findings from this study might be applicable to stem cells in other systems.
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http://dx.doi.org/10.1038/ncomms9856 | DOI Listing |
Stem Cell Res Ther
January 2025
Shenzhen Key Laboratory of Epigenetics and Precision Medicine for Cancers, Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, China.
Background: Patient-derived lung cancer organoids (PD-LCOs) demonstrate exceptional potential in preclinical testing and serve as a promising model for the multimodal management of lung cancer. However, certain lung cancer cells derived from patients exhibit limited capacity to generate organoids due to inter-tumor or intra-tumor variability. To overcome this limitation, we have created an in vitro system that employs mesenchymal stromal cells (MSCs) or fibroblasts to serve as a supportive scaffold for lung cancer cells that do not form organoids.
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January 2025
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.
Background: The role of hospital pharmacists in managing cell and gene therapy (CGT) and advanced therapy medicinal products (ATMPs) is gradually being recognized but the evidence about impact of their role has not been systematically reported.
Objective: This study was aimed to summarize the professional services provided by hospital pharmacists on managing CGT/ATMPs and the evidence about the effects on patient care, as well as to identify the perceptions about pharmacists assuming a role that supports the appropriate and safe use of CGT/ATMPs.
Methods: Literature from 4 electronic databases (PubMed, ScienceDirect, Web of Science, Scopus) were searched following PRISMA checklist to yield publications on the interventions provided by hospital pharmacists in the management of CGT/ATMPs dated since 1 January 2013 till 30 April 2023.
Eur J Haematol
January 2025
Institute of Clinical Medicine, Oncology, University of Eastern Finland, Kuopio, Finland.
Purpose: The prognosis of relapsed primary central nervous system lymphoma remains a concern. This study aimed to compare the effects of various patient- and disease-related factors on the prognosis of relapsed primary central nervous system lymphoma (PCNSL).
Methods: We retrospectively collected real-world data from eight Finnish hospitals on 198 patients diagnosed with PCNSL between 2003 and 2020.
Nat Immunol
January 2025
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Hematopoietic stem cells must mitigate myriad stressors throughout their lifetime to ensure normal blood cell generation. Here, we uncover unfolded protein response stress sensor inositol-requiring enzyme-1α (IRE1α) signaling in hematopoietic stem and progenitor cells (HSPCs) as a safeguard against myeloid leukemogenesis. Activated in part by an NADPH oxidase-2 mechanism, IRE1α-induced X-box binding protein-1 (XBP1) mediated repression of pro-leukemogenic programs exemplified by the Wnt-β-catenin pathway.
View Article and Find Full Text PDFAnn Hematol
January 2025
Division of Hematopoietic Disease Control, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
The prognosis of adult T-cell leukemia/lymphoma (ATL) with primary central nervous system (CNS) involvement has been unclear since the advent of new therapies. Recently, we have shown that flow cytometric CD7/CADM1 analysis of CD4 + cells (HAS-Flow) is useful to detect ATL cells that are not morphologically diagnosed as ATL cells. We investigated the role of CNS involvement in ATL using cytology and HAS-Flow by analyzing cerebrospinal fluid (CSF) from 73 aggressive ATL cases.
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