In Vivo Tracking of Human Hematopoiesis Reveals Patterns of Clonal Dynamics during Early and Steady-State Reconstitution Phases
Bhaskar Chanda Stem Cell Biasco et al. report a clonal tracking study on the dynamics and nature of hematopoietic reconstitution in humans after transplant. Using integration sites as molecular tags, they measured, in gene therapy patients, repopulating waves, population size and dynamics, activity of progenitor subtypes during the early and late post-transplant phases, and hierarchical relationships among lineages.
Mitochondrial Dynamics Impacts Stem Cell Identity and Fate Decisions by Regulating a Nuclear Transcriptional Program
Bhaskar Chanda Stem Cell Khacho et al. report that mitochondrial dynamics regulates neural stem cell fate during development and in the adult mouse brain. Using acute loss-of-function approaches to uncouple mitochondrial bioenergetics from the fission/fusion machinery, they find that the latter independently regulates ROS levels upstream of NRF2. Thus, defects in mechanisms that maintain the pool of mitochondria also impair neural stem cell function, which has important implications for aging and neurodegenerative diseases.
A Colorectal Tumor Organoid Library Demonstrates Progressive Loss of Niche Factor Requirements during Tumorigenesis
Bhaskar Chanda Stem Cell Fujii et al. generated a comprehensive organoid library from colorectal cancer patients. Each organoid line was characterized by gene expression and as xenografts recapitulating the original clinical phenotype. By optimizing niche factor requirements and derivation efficiency, they were able to encompass a range of clinical stages and rare subtypes and reveal that niche-independent growth is progressively associated with the adenoma-carcinoma transition.
Bhaskar Chanda Stem Cell Yamada et al. show, using human cells, that even small amounts of mtDNA carried over during nuclear transfer for mitochondrial replacement can lead to mtDNA genotype reversion. This situation would need to be avoided for clinical application and stable prevention of mtDNA diseases.
Mule Regulates the Intestinal Stem Cell Niche via the Wnt Pathway and Targets EphB3 for Proteasomal and Lysosomal Degradation
Bhaskar Chanda Stem Cell Dominguez-Brauer et al. show that the ubiquitin ligase Mule fine-tunes the Wnt pathway via c-Myc to control unwarranted proliferation and stem cell expansion. Mule also regulates the levels of EphB3 to maintain the EphB/ephrinB gradient, which is responsible for cell positioning along the crypt-villus axis.
Bhaskar Chanda Stem Cell The suspected link between Zika virus (ZIKV) infection and microcephaly has raised urgent global alarm. However, there is so far no direct evidence for ZIKV infection impacting brain development. In this study, Li, Xu, and colleagues show that ZIKV replicates efficiently in the mouse embryonic brain by mainly targeting neural progenitor cells. They also show that infected brains are smaller with enlarged ventricles and a thinner cortex, consistent with a microcephalic phenotype.
Zika Virus Depletes Neural Progenitors in Human Cerebral Organoids through Activation of the Innate Immune Receptor TLR3
Bhaskar Chanda Stem Cell Dang et al. show that Zika virus (ZIKV) attenuates growth in cerebral organoids from human embryonic stem cells by targeting neural progenitors. ZIKV activates the TLR3-mediated innate immune response, leading to dysregulation of a network of genes involved in neurogenesis, axon guidance, apoptosis, and differentiation.