bims-minfam 2023-10-22 papers

Cell Stem Cell. 2023 Oct 16. pii: S1934-5909(23)00358-2. [Epub ahead of print]

SRCAP mutations drive clonal hematopoiesis through epigenetic and DNA repair dysregulation.

Somatic mutations accumulate in all cells with age and can confer a selective advantage, leading to clonal expansion over time. In hematopoietic cells, mutations in a subset of genes regulating DNA repair or epigenetics frequently lead to clonal hematopoiesis (CH). Here, we describe the context and mechanisms that lead to enrichment of hematopoietic stem cells (HSCs) with mutations in SRCAP, which encodes a chromatin remodeler that also influences DNA repair. We show that SRCAP mutations confer a selective advantage in human cells and in mice upon treatment with the anthracycline-class chemotherapeutic doxorubicin and bone marrow transplantation. Furthermore, Srcap mutations lead to a lymphoid-biased expansion, driven by loss of SRCAP-regulated H2A.Z deposition and increased DNA repair. Altogether, we demonstrate that SRCAP operates at the intersection of multiple pathways in stem and progenitor cells, offering a new perspective on the functional impact of genetic variants that promote stem cell competition in the hematopoietic system.

Keywords: DNA damage; H2A.Z; SRCAP; chromatin remodeling; clonal hematopoiesis; hematopoietic stem cells; lymphoid

DOI: https://doi.org/10.1016/j.stem.2023.09.011

Cold Spring Harb Perspect Med. 2023 Oct 17. pii: a041193. [Epub ahead of print]

Roles of NAD+ in Health and Aging.

Sofie Lautrup, Yujun Hou, Evandro F Fang, Vilhelm A Bohr.

NAD+, the essential metabolite involved in multiple reactions such as the regulation of cellular metabolism, energy production, DNA repair, mitophagy and autophagy, inflammation, and neuronal function, has been the subject of intense research in the field of aging and disease over the last decade. NAD+ levels decline with aging and in some age-related diseases, and reduction in NAD+ affects all the hallmarks of aging. Here, we present an overview of the discovery of NAD+, the cellular pathways of producing and consuming NAD+, and discuss how imbalances in the production rate and cellular request of NAD+ likely contribute to aging and age-related diseases including neurodegeneration. Preclinical studies have revealed great potential for NAD+ precursors in promotion of healthy aging and improvement of neurodegeneration. This has led to the initiation of several clinical trials with NAD+ precursors to treat accelerated aging, age-associated dysfunctions, and diseases including Alzheimer's and Parkinson's. NAD supplementation has great future potential clinically, and these studies will also provide insight into the mechanisms of aging.

DOI: https://doi.org/10.1101/cshperspect.a041193

Redox Biol. 2023 Oct 13. pii: S2213-2317(23)00325-7. [Epub ahead of print] 102924

Corrigendum to "Cholesterol confers ferroptosis resistance onto myeloid-biased hematopoietic stem cells and prevents irradiation-induced myelosuppression" [Redox Biol. 62 (2023) 102661].

Chaonan Liu, Weinian Liao, Jun Chen, Kuan Yu, Yiding Wu, Shuzhen Zhang, Mo Chen, Fang Chen, Song Wang, Tianmin Cheng, Junping Wang, Changhong Du.

DOI: https://doi.org/10.1016/j.redox.2023.102924

N Engl J Med. 2023 Oct 19. pii: 10.1056/NEJMc2309139#sa1. [Epub ahead of print]389(16): 1535

Familial Clonal Hematopoiesis in a Long Telomere Syndrome.

Tetsushi Nakao, Pradeep Natarajan.

DOI: https://doi.org/10.1056/NEJMc2309139

N Engl J Med. 2023 Oct 19. pii: 10.1056/NEJMc2309139#sa2. [Epub ahead of print]389(16): 1535-1536

Familial Clonal Hematopoiesis in a Long Telomere Syndrome. Reply.

Mary Armanios.

DOI: https://doi.org/10.1056/NEJMc2309139