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Ali and colleagues characterize the differentiation of cone photoreceptors in mESC retinal organoids, showing substantial numbers of committed cone precursors. Their differentiation is negatively regulated by the Notch pathway, expression of Nrl and Nr2e3, and high concentrations of retinoic acid. Isolated and transplanted into a severely degenerated retina, these cone precursors survive and express markers of advanced maturation.
In this article, Huang and colleagues show that the default tumor type arising from p53 knockout mouse bone marrow-derived mesenchymal stem cells is osteoblastic osteosarcoma (OS), and oncogenic signals can override this default tumor type choice. They focus on studying the mechanisms underlying cFOS-driven chondroblastic OS and demonstrate that SOX9 is one of the mediators of cFOS.
Phillippi and colleagues classified the surface proteome of perivascular progenitor cells in human ascending aorta and revealed their localization to the vasa vasorum. Purified pericytes demonstrated potential for smooth muscle cell differentiation and an association with branching endothelial cells in vitro.
Oligodendrocyte precursor cells (OPCs) have broad potential for cell therapy; however, differentiating them at scale from human pluripotent stem cells remains challenging. Schaffer and colleagues established a NKX2.2-EGFP hESC reporter line that facilitated the development of a 3D system for directed differentiation of OPCs, which even without cell selection could migrate and mature into oligodendrocytes after implantation into NOD/SCID mice.
In this article, Dekel and colleagues use flow cytometry and single-cell analysis to show that human fetal kidney cultured in modified nephron progenitor expansion medium (mNPEM) preserves all major nephric developmental lineages (including the Cap mesenchyme, early epithelial progeny, differentiated epithelium, and mesenchymal-to-epithelial-transition states). The biomarker system they developed allows distinguishing between early nephric lineages in expanded nephron stem cell cultures affording prospective isolation.
In this article, Ying, He, and colleagues show that Adriamycin-based chemotherapeutics may simulate CSCs through activation of KLF4 signaling and that selective inhibition of KLF4 with statins, the cholesterol-lowering agents, remarkably reverse the Adriamycin-induced CSC properties and metastasis in osteosarcoma. Their findings suggest that targeting of KLF4 with statins may be considered in the development of osteosarcoma therapeutics.
Godlewski and colleagues show that microRNAs, unlike long non-coding RNAs and protein-coding mRNAs, do not correlate with glioblastoma tissue subtype classification, and that heterogeneous expression of microRNAs observed in subtypes is further propagated by intratumoral exchange of extracellular vesicles (EVs). Cellular and EV microRNAs display cell-specific functions by targeting cell subpopulation-specific effectors, allowing cell adaptation to diverse tumor anatomic niches.
Douvaras and colleagues generated microglia from pluripotent stem cells using a chemically defined protocol through a myeloid progenitor. iPSC-derived microglia showed highly motile processes, were able to phagocytose and responded to ADP with calcium transients. Microglial identity was further confirmed by gene expression analysis comparing multiple iPSC-derived microglia samples with primary microglia and peripheral blood or other tissue-specific macrophages.
In this report, Perlingeiro and colleagues test a chemically defined monolayer (CDM) differentiation protocol and find that it generates a heterogeneous myogenic cell population that does not contribute to myofiber formation in vivo. They demonstrate that conditional expression of PAX7 enables the expansion of a homogeneous population of myogenic progenitors that have in vivo regenerative potential.
In this study, we induce differentiation and maturation of mouse and human embryonic stem cell (ESC)-derived cardiomyocytes (CMs) by the application of defined pulsatile flow and cyclic strain in a custom-made bioreactor. The ESC-CMs cultured under dynamic conditions and extended culture time showed a significantly faster calcium decay, increased SERCA activity and sarcomeric length, as well as protein and gene expression patterns, and biochemical fingerprints comparable with primary CMs.
Ee and colleagues characterize an embryonic stem cell (ESC)-specific isoform of the Mbd3 subunit of the NuRD chromatin remodeling complex. This variant, called Mbd3c, forms a variant NuRD complex that incorporates the histone binding protein Wdr5, and this interaction is critical for its functions in gene regulation. The presence of either Mbd3c/NuRD or canonical NuRD complex (containing either the Mbd3a or Mbd3b isoform) is necessary for normal gene regulation and ESC pluripotency.
In this article, Díaz de la Guardia and colleagues report a functional, genetic, and immunological characterization of BM-MSC cultures from 46 AML patients, stratified by molecular/cytogenetics into low-risk (LR), intermediate-risk (IR), and high-risk (HR) subgroups. BM-MSCs never harbored tumor-specific cytogenetic/molecular alterations present in blasts, and IL-10 produced by AML-derived BM-MSCs is an independent prognostic factor negatively impacting on overall survival.
Cheung and colleagues identify a transient state of osteo-chondroprogenitor-like cells during the course of chondrogenic reprogramming. These osteo-chondrogenic cells exhibit a gene expression profile akin to that of native osteo-chondroprogenitors with elevated osteogenic potency in vivo. Therefore, this study provides a reprogramming strategy to generate osteo-chondrogenic cells that might be useful for cell-based therapy not limited to cartilage but also for bone tissues.
In this article, Zhou, Hao, and colleagues generate two completely xeno-free clinical-grade human embryonic stem cell lines which have demonstrated pluripotency and biosafety under the investigation from an accredited organization.
In this article, Hsieh and colleagues use AAV9 viral infection to selectively target and overexpress NEUROD1 in astrocytes in the absence of injury to the CNS. The authors show that NEUROD1 is capable of converting a small, but significant number of astrocytes to neurons in vivo in the absence of reactive gliosis.
In this article, Gerbaulet and colleagues report on SCA-1 expression level as a marker for prospective isolation of quiescent cells with elevated repopulation potential not only in hematopoietic stem cells but also in progenitor populations. They show that high SCA-1 expression by quiescent hematopoietic stem and progenitor cells is independent of type I interferon signaling.
In this article, Cho and colleagues show that an efficient strategy for producing directly an unlimited supply of functional human Schwann cells (SCs) via successful derivation of expandable Schwann cell precursors (SCPs) from human pluripotent stem cells (hPSC-SCPs). Functional and molecular characteristic of SCs from hPSC-SCPs (SCP-SCs) were shown both in vitro and in vivo.
In this article, Lund and colleagues show that RNA polymerase III subunit G (POLR3G) regulates a specific subset of transcriptome in human pluripotent stem cells. The primary function of POLR3G is in the maintenance of transcription. Among the direct targets of POLR3G is mtDNA polymerase γ, with potential importance in maintenance of stem cell state in a POLR3G-dependent manner.
In this article, Arthur and colleagues show how expression of the TGFβ co-receptor endoglin is essential for the paracrine pro-angiogenic properties of cardiosphere-derived cells, a heterogeneous stem cell population derived from the heart.
In this article, Rodriguez-Perales and colleagues show an efficient CRISPR approach for recreating cancer-associated chromosome translocations in human stem cells. They generate the Ewing sarcoma t(11;22) translocation in human mesenchymal and induced pluripotent stem cells using RNPs and ssODNs. The generation of targeted translocations in human stem cells opens up new avenues in modeling Ewing sarcoma and human neoplasias.