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In this study, Lee and colleagues show that simple VC treatment during donor NSC preparation enhances cell therapeutic outcomes in a PD animal model, along with enriched midbrain DA neuron engraftment. The VC effect was achieved by a long-lasting epigenetic activation of midbrain DA neuron-specific developmental and phenotype gene expressions via DNA and repressive histone code demethylation.
In this article, Knöbel and colleagues identified IAP as a cell surface marker for mesDA progenitor cells. Immunomagnetic sorting for IAP+ led to reproducible and homogeneous cell compositions. Intrastriatal transplantation of sorted cells at day 16 of differentiation in a PD rat model resulted in functional recovery, and grafts were more homogeneous in size and DA neuron density than unsorted cells.
Richardson et al. demonstrate the biphasic nature of corneal epithelial development during late embryogenesis. Progenitor cells of the central cornea are lost during post-natal life, replaced by those in the peripheral limbus, whose age-related dynamics align with population asymmetry. Apoptosis within the central corneal epithelium alters normal clonal migration patterns.
In this article, Wiper-Bergeron and colleagues demonstrate that the transcription factor SOX7 is required for skeletal muscle satellite cell development and maintenance. SOX7 regulates Pax7 expression, and loss of SOX7 leads to fewer satellite cells that are more sensitive to apoptosis. Furthermore, loss of Sox7 in satellite cells results in smaller myotubes and impaired regeneration after injury in post-natal muscle.
Ploubidou and colleagues assess the impact of misorientation of the mitotic spindle of neuronal progenitor cells on brain development. They employ a spindle misorientation model expressing truncated RHAMM, exhibiting no centrosome biogenesis or spindle assembly defects in vivo. The data demonstrate that spindle misorientation in cerebellum and cerebrum neuroprogenitors results in megalencephaly and that RHAMM regulates differentiation in the developing brain.
In this article, Kazuki and colleagues show that spermatogonial stem cells can maintain a minichromosome vector more stably than ESCs, which often undergo karyotype abnormalities and loss of minichromosomes during long-term culture. Because transchromosomic mice can be produced in F1 generation, this method overcomes problems associated with previous methods using ESCs and provides new possibilities for germline manipulation.
Tsukada et al. demonstrate that teratomas formed in vivo by Gfi1b-, c-Fos-, and Gata2-overexpressing iPSCs give rise to functional, long-term HSCs. Teratoma-derived HSCs and hematopoietic cells were detected in peripheral blood, expanded to the bone marrow after depletion of host HSCs, and showed successful engraftment in serial transplantation assays. This work underscores the importance of evaluating differentiation strategies in vivo.
Elevated prolactin correlates with increased risk for aggressive breast cancers expressing ERα. In a transgenic mouse model with high mammary prolactin, Schuler and colleagues demonstrate expanded progenitor/stem epithelial populations and impeded steroid-induced luminal cell maturation, associated with altered transcriptional networks to perturb differentiation, which may underlie its contributions to this disease.
In this article, Honoré, Grapin-Botton, and colleagues use single-cell expression profiling to show a differentiation sequence from hESCs to pancreatic endocrine cells and early divergence of paths to different endocrine subtypes. Two paths lead to β-cell differentiation where NKX6.1 can be initiated before or after endocrine commitment.
Hackland and colleagues have developed a method for the generation of human neural crest cells that allows their use in clinical applications. Their method allows for greater control over the environment of the cells by managing the influence of cell-produced signals, and this approach could be applied to other systems.
In this article, Zeller and colleagues show that functionally distinct MSC populations arise at specific time points during mouse embryonic limb and long bone development and persist during homeostasis. In particular, a PαS subpopulation with the ability to form well-structured bone organoids encompassing functional endothelial and hematopoietic compartments is identified, which is of relevance for bone tissue engineering.
In this article, Baharvand and colleagues provided a platform to discover influential genes and cellular events involved in transition from the ICM cells to embryonic stem cells (ESCs) by applying gene expression profiling from the ICM cells, various stages of ICM outgrowths, and early to further passages of ESCs.
Extraembryonic endoderm stem (XEN) cell lines can be derived and maintained in vitro and reflect the primitive endoderm lineage. Platelet-derived growth factor receptor alpha has been thought to be essential for the derivation and maintenance of mouse XEN cell lines. Mombaerts and colleagues have re-evaluated this requirement and conclude that it is not the case.
Ying-Shing Chan and colleagues demonstrate that the human bone marrow harbors neuro-ectodermal progenitors that can be enriched, expanded, and directed to differentiate into functionally mature, fate-committed SCs. This work holds promise for further development into an autologous cell source for implantation as a treatment strategy for nerve injuries or peripheral neuropathies.
In this article, Mourkioti and colleagues develop a telomere assay named MuQ-FISH and show that the critical telomere shortening of muscle stem cells from boys with Duchenne muscular dystrophy contributes to the progressive dysfunction that compromises their regenerative potential.
Here, Niclis and colleagues have used a human Pitx3-GFP embryonic stem cell line to map patterns of connectivity of transplanted DA neurons in a rat model of Parkinson’s disease. The results show that stem cell-derived DA neuronal subtypes innervate developmentally appropriate targets but also that contemporary differentiation and transplantation procedures yield grafts with extensive patterns of non-DA growth.
In this article, Hobbs and colleagues characterize a critical role for the transcription factor SALL4 in maintenance of undifferentiated spermatogonia in the testis. While undifferentiated cells initially tolerated acute Sall4 deletion, they were progressively depleted over time. SALL4 regulated undifferentiated cell function by repressing Dusp4 and Foxl1, which suppressed cell proliferation and survival and blocked self-renewal signals when aberrantly expressed.
Organoids derived from human pluripotent stem cells (hPSCs) represent an attractive system for investigating human development and disease in vitro. Nadkarni et al. show that hPSC-derived cystic intestinal organoids, or enterospheres, have a uniform epithelial structure, are easily accessible to genetic modification, and contain functional intestinal cell types that provide an in vitro modeling system for studying human gastrointestinal biology.
In this article, Kawamoto and colleagues show that NK cells derived from an HLA-hetero individual killed the cells regenerated from HLA-homo iPSCs in KIR ligand-mismatched cases, by sensing the lack of KIR ligand expression. Such cytotoxicity was cancelled when regenerated cells are enforced to express the missing KIR ligand, providing a novel approach to prevent NK cell-mediated rejection.
In this study, Parmar, Ottosson, and colleagues show how endogenous NG2 glia can be reprogrammed into GABAergic interneurons of different subtypes, the majority of them with properties of fast-spiking parvalbumin-containing interneurons. This neuronal subtype has been implicated in several neurological diseases, and the findings can open up new therapeutic options.