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Reaching the Holy Grail: Making Hematopoietic Stem Cells in a Dish.
Cell Reprogram
December 2024
San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy.
The successful generation of long-term engrafting hematopoietic stem cells (HSCs) from human-induced pluripotent stem cells (hiPSCs) has long been sought to revolutionize treatments for hematological disorders, eliminating reliance on donors and avoiding immune rejection, and thus has been seen as a major milestone in regenerative medicine. Previous studies, guided by developmental hematopoiesis, made progress in creating blood cells from hiPSCs, but challenges persisted in producing hematopoietic cells with functional properties of genuine HSCs capable of long-term engraftment. In their recent study, Ng and colleagues described an optimized differentiation protocol that manipulates key signaling pathways, including TGF-β, WNT, BMP, and retinoic acid in a stage-specific manner to generate HSCs with multilineage capacity.
View Article and Find Full Text PDFEmerging role of microglia in the developing dopaminergic system: perturbation by early life stress.
Neural Regen Res
November 2024
Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong Province, China.
Early life stress correlates with a higher prevalence of neurological disorders, including autism, attention-deficit/hyperactivity disorder, schizophrenia, depression, and Parkinson's disease. These conditions, primarily involving abnormal development and damage of the dopaminergic system, pose significant public health challenges. Microglia, as the primary immune cells in the brain, are crucial in regulating neuronal circuit development and survival.
View Article and Find Full Text PDFPhysioxia rewires mitochondrial complex composition to protect stem cell viability.
Redox Biol
November 2024
Institute of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. Electronic address:
Human induced pluripotent stem cells (hiPSCs) are an invaluable tool to study molecular mechanisms on a human background. Culturing stem cells at an oxygen level different from their microenvironmental niche impacts their viability. To understand this mechanistically, dermal skin fibroblasts of 52 probands were reprogrammed into hiPSCs, followed by either hyperoxic (20 % O) or physioxic (5 % O) culture and proteomic profiling.
View Article and Find Full Text PDFSmall Molecule-Mediated Stage-Specific Reprogramming of MSCs to Hepatocyte-Like Cells and Hepatic Tissue for Liver Injury Treatment.
Stem Cell Rev Rep
November 2024
Stem Cell and Molecular Biology, Laboratory, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, Tamil Nadu, 600036, India.
Background: Derivation of hepatocytes from stem cells has been established through various protocols involving growth factor (GF) and small molecule (SM) agents, among others. However, mesenchymal stem cell-based derivation of hepatocytes still remains expensive due to the use of a cocktail of growth factors, and a long duration of differentiation is needed, thus limiting its potential clinical application.
Methods: In this study, we developed a chemically defined differentiation strategy that is exclusively based on SM and takes 14 days, while the GF-based protocol requires 23-28 days.
Transient chromatin decompaction at the start of male embryonic germline development.
Life Sci Alliance
October 2024
Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
Embryonic germ cells develop rapidly to establish the foundation for future developmental trajectories, and in this process, they make critical lineage choices including the configuration of their unique identity and a decision on sex. Here, we use single-cell genomics patterns for the entire embryonic germline in along with the somatic gonadal precursors after embryonic gonad coalescence to investigate molecular mechanisms involved in the setting up and regulation of the germline program. Profiling of the early germline chromatin landscape revealed sex- and stage-specific features.
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