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Welby et al. define a cone-enriched gene signature within a human fetal L/M-opsin cone population, which is used as a baseline reference to demonstrate similar cone gene expression between bona fide and stem cell-derived L/M-opsin cone cells. Furthermore, profiling of cell surface molecules in human fetal cones led to the generation of a cluster of differentiation marker panel, which provides enrichment of fetal and stem cell-derived cones.
In this article, Bae and colleagues show that JNKs directly interact with and phosphorylate OCT4 at serine 347. This phosphorylation inhibits the transcriptional activity and stability of OCT4 in mouse ESCs. The mutant OCT4 (S347A) might delay the differentiation process of mouse ESCs and enhance the efficiency of generating iPSCs.
In this article, Koistinaho and colleagues reveal that astrocytes from PSEN1 ΔE9 patients display a severe AD-related phenotype, including increased Aβ production, altered mitochondrial metabolism, and reduced lactate secretion. Furthermore, PSEN1 ΔE9 astrocytes influence the calcium signaling activity of healthy neurons. The results highlight the importance of astrocytes in AD pathogenesis.
In this article, Muratore et al. examine differential vulnerability of neuronal subtypes in AD by directing iPSC lines from control and familial AD subjects to different regional neuronal fates. APP processing and TAU proteostasis are differentially affected between regional fates, such that neuronal cell type dictates generation of and responsiveness to Aβ.
Zhu and colleagues successfully induce mouse syncytiotrophoblast (SynT) layer II cells from trophoblast stem cells by activation of canonical Wnt signaling. The induced SynT-II cells are migratory and are dependent on HGF/c-MET pathway. The availability of SynT-II cells in vitro should facilitate molecular study of labyrinth layer development in placenta.
Siegel and colleagues describe their development of a human and mouse intestinal epithelial cell monolayer platform that maintains the cellular, molecular, and functional characteristics of tissue for each intestinal segment. They demonstrate the platform's application to drug discovery by screening a library of over 2,000 compounds to identify an inhibitor of potassium ion transport in the mouse distal colon.
In this issue of Stem Cell Reports, Braccioli et al. describe how FOXP1 promotes embryonic neural stem cell differentiation both in vitro and in vivo by transcriptionally regulating pro-neural genes and by repressing the Notch-ligand Jagged1.
In this article, Ishikawa and colleagues show that miRNAs can regulate early cell-fate decisions during differentiation of human ESCs. miRNome profiling in pure endoderm and mesoderm revealed differentially expressed miRNAs. The endoderm-specific miR-489-3p and miR-1263 increased endoderm specification. The miR-1263 effect was mediated by KLF4 repression. The mesoderm-specific miR-483-3p regulated the generation PDGFRA+ paraxial cells via PGAM1 repression.
In this article, Zhao and colleagues show that expression of miR-302 is sufficient to enable neural differentiation of differentiation-incompetent Dgcr8−/− ESCs. The authors demonstrated that miR-302 directly suppresses p53, which serves as a barrier restricting neural differentiation.
In this article, Ebert and colleagues show that iPSC-derived dopaminergic neurons expressing the LRRK2 G2019S mutation exhibit mitochondrial abnormalities, reduced sirtuin activity, and low endogenous NAD+ levels compared with other neuronal subtypes generated from the same patient samples. Therefore, the distinct sirtuin and bioenergetic deficiencies intrinsic to dopaminergic neurons may underlie dopaminergic neuron loss in Parkinson's disease.
Ground-state pluripotency is a cell state in which pluripotency is maintained through inhibition of differentiation. In this paper, Baharvand and colleagues report that ground-state pluripotency is associated with a unique microRNA signature. They find that ground-state microRNAs, which are mostly encoded by the Dlk1-Dio3 locus, contribute to the maintenance of ESCs through stimulating self-renewal and inhibiting differentiation.
Kisa et al. modified several methods for converting human induced pluripotent stem cells (hiPSCs) into a naive state, a form of pluripotency that exists in mouse embryonic stem cells (ESCs). Converted cells express components of the core transcriptional network upregulated in mouse ESCs, including ESRRB. They also show that these cells differentiate more readily into neural cells than do conventional hiPSCs.
Wu and colleagues demonstrate that adult endogenous neural stem cells in three key brain regions have individual responses to alcohol consumption. Further, they show that these regional changes are affected by the sex of mice.
Temple and colleagues show through a multi-time-point study that age-associated changes in gene expression and cell behavior in the adult V-SVZ are predominantly non-monotonic. While neurogenesis declines with aging, the number and cell division rate of transit-amplifying progenitor cells declines to 18 months and then surprisingly increases between 18 and 22 months. Furthermore, they demonstrate that these behaviors are recapitulated in single progenitor cells growing in clonal culture, indicating that age-associated changes are programmed and niche independent.
In this article, Zheng and colleagues show that inducible RHOA deletion in mice causes defects in intestine epithelial polarity and deficiencies in intestinal stem cell proliferation, survival, and regeneration. They further demonstrate by genetic rescues that RHOA controls a YAP-EREG axis to mediate canonical Wnt signaling, intestinal stem cell function, and intestinal homeostasis.
In this article, Sugita and colleagues show that B cells, as well as T cells, are associated with immune attack on iPSC-derived retinal pigment epithelial cells (RPE) after allogeneic transplantation. In addition, it shows that B cells can produce alloantibodies against iPSC-RPE cells.
Mujoo and colleagues demonstrate that ESC- or iPSC-derived differentiated cells exhibit higher frequency of residual DNA damage, increased 53BP1 foci and S-phase-specific chromosomal aberrations, and reduced formation of RAD51 or BRCA1 foci. Differentiated cells also had relatively increased stalled DNA replication forks and decreased firing of new replication origins. NO donor treatment decreased DSB repair by HR but not by NHEJ.
Tan et al. show that a more stable epigenome contributes to the resistance of NMR iPSCs to OSKM reprogramming. Reprogramming is facilitated by inactivation of Rb, which leads to opening of promoters of reprogramming genes.
In this article, Gialitakis and colleagues show that activation of the transcription factor AHR affects lineage decisions in embryonic stem cells. Activated AHR interacts with the NuRD complex and thereby transiently disrupts early stages of differentiation. Environmental pollutants that are poorly metabolized prolong the normally tightly controlled AHR activity and could therefore have adverse effects on mammalian development.
Simple treatment with three small molecules enhanced hPSC differentiation into three germ layers, namely CTraS. CTraS reduced the innate differentiation propensities of hPSCs and shifted them into terminal differentiations. CTraS induction accelerated in vitro pathological expression with maturation and aging. Thus, CTraS can bring out the latent potential of hPSCs.