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Updated: 6 hours 32 min ago
In this article, Clark and colleagues show that both primed and naive hESCs are compatible with a TRIM28 deletion, despite massive deregulation of transposable elements. However, human germline competency and paternal imprint methylation are compromised upon loss of TRIM28.
In this article, Zhao and colleagues demonstrated that TET2 plays an important role in regulating the behavior of BMSCs in addition to its intrinsic role in HSPCs to participate in aberrant hematopoiesis. Moreover, they also show that BMSCs are the most important niche cell components in Tet2−/− mice that contribute to the progression of Tet2-deletion-driven myeloid malignancies.
Kauts et al. demonstrate that Gata2Venus, Ly6aGFP, and double reporter expression in differentiating mouse embryonic stem cells (ESCs) discriminates and facilitates enrichment of most hematopoietic progenitors generated in vitro. Sequential waves of ESC-derived reporter cell emergence show increasing hematopoietic lineage potency and approximate the in vivo waves of hematopoietic cell generation found in the mouse embryo.
Chen et al. found that BMAL1 expression decreased significantly in the mandibles of juvenile SMH patients, and SMH was observed in circadian-rhythm-disrupted mice or Bmal1−/− mice. Moreover, they demonstrated that MMP3 is an indispensable factor in BMAL1-deficiency-induced SMH. Given these findings, they set out to characterize the underlying mechanism and found that BMAL1 deficiency enhanced Mmp3 transcription through activating p65 phosphorylation.
In this article, Tang and colleagues, by using an unbiased bigenic mouse model to specifically earmark, prospectively isolate, and functionally characterize the quiescent stem-like cells, report a label-retaining cell (LRC) population in the mouse prostate luminal cell layer that possesses many stem/progenitor cell activities. These luminal LRCs are developmentally bipotent and intrinsically castration resistant.
Richmond et al. demonstrate that, following intestinal inflammatory injury, reserve intestinal stem cells (r-ISCs) exit quiescence and contribute to intestinal regeneration. In contrast, crypt base columnar ISCs undergo apoptosis and show a reduced lineage contribution in the immediate recovery period. JAK/STAT-1 signaling is required for r-ISC activation during the early recovery period following inflammatory injury.
In this article, Rongwen Xi and Chang Yin show that, in adult Drosophila midgut, the Sina-Phyl-Ttk69 complex and Scute form a positive feedback regulatory loop to drive cell fate commitment from enteroendorine cell progenitor cells. The findings provide important insights into faithful cell fate commitment from multipotent stem cells.
How PMP22 duplication leads to CMT1A neuropathy remains to be elucidated. In this article, Yao, Li, and colleagues show that neural crest stem cells (NCSCs) derived from CMT1A hiPSCs have developmental disabilities of Schwann cells; in contrast, CMT1A NCSCs generate numerous endoneurial fibroblast-like cells in the Schwann cell differentiation system.
In this article, Jason Spence and colleagues identify a core signaling network that maintains isolated human epithelial lung bud tip progenitors in vitro and that induces a bud tip-like population from hPSCs. They show that iPSC-derived bud tip progenitors can engraft into an injured mouse airway, contribute to re-epithelialization, and differentiate into multiple lung epithelial lineages.
Neehus and colleagues describe the simultaneous generation of genetically diverse patient-specific iPSC lines from one chimeric patient with Mendelian susceptibility to mycobacterial disease (MSMD) due to IFNγR1 deficiency. Hematopoietic differentiation toward macrophages of heterozygous and compound heterozygous MSMD iPSC lines laid the foundation to study IFNγ signaling and susceptibility to mycobacterial infections of patient-derived macrophages.
Yi et al. describe HN1L as a novel transcription regulator for breast cancer stem cells (BCSCs) in triple-negative breast cancer (TNBC), promoting LEPR and miR-150 expression and activating the STAT3 pathway. Since BCSCs contribute to chemoresistance and metastasis in TNBC, further investigation of HN1L will offer new therapeutic strategies.
Wang and colleagues show that the GCN5 lysine acetyltransferase regulates FGF signaling at multiple levels in early ESC differentiation and is essential for mesodermal lineage formation in vitro. Gcn5 loss leads to downregulation of specific genes involved in signaling and metabolism in an H3K9ac-dependent manner, including discrete MYC gene targets.
In this article, Zandstra and colleagues have identified FZD4 as a new marker for lateral plate mesoderm. Using FZD4, they showed an increase in cardiac progenitor cell purity and a subsequent increase in cardiomyocyte induction in both the mouse and human systems. These findings demonstrate a role for FZD4 in mammalian cardiac development.
In this article, Nishihara and colleagues show that PKCζ is modified by O-GlcNAc and that O-GlcNAc on PKCζ inhibits PKCζ phosphorylation (activation) in mouse embryonic stem cells (ESCs). Phosphorylated PKCζ phosphorylates MEK-ERK1/2 via FGF4 stimulation, and phosphorylated ERK1/2 induces ESC differentiation. Inhibition of PKCζ phosphorylation by O-GlcNAc resulted in the inhibition of the FGF4 signal in ESCs.
Ishibashi et al. report the contribution of ATOH1+ intestinal epithelial cells to the maintenance, regeneration, and tumorigenesis in the colon. They find that a definite number of ATOH1+ intestinal epithelial cells retain stem cell properties under homeostatic conditions. Also, generation of ATOH1+ cell-derived stem cells is significantly enhanced by the inflammatory environment and contributes to the development of colitis-associated tumors.
Human GMP-grade neural stem cell transplantation rescues behavioral deficits and electrophysiological alterations in Huntington's disease mice, and rescue is associated with reduced accumulation of mutant Huntingtin protein.
Takahashi et al. developed several user-friendly culture methods for human induced pluripotent stem cell (iPSC)-derived intestinal organoids. The methodological improvements include preparation of conditioned medium for organoid culture, efficient differentiation from iPSCs, gene transduction in organoids, and growth in suspension culture. This system will facilitate high-throughput screening of pathogenic factors and treatments for intestinal diseases using physiologically robust intestinal organoids.
In this article, Newgreen and colleagues show that human pluripotent cells can be induced to form chromaffin-like cells, which produce adrenaline and noradrenaline in vitro. The method uses the dual-inhibitor method to induce neural crest progenitor and sympathoadrenal-like cells then extended BMP4 and corticosteroid exposure for the chromaffin-like stage, with curtailed FGF2 exposure to limit sympathetic neuron induction.
Because breast-conserving surgeries are popular among breast cancer patients, studying the “normal” tissue remaining after the surgery is important for understanding how this tissue is primed to promote the growth of residual tumor cells. In this article, Raouf and colleagues show that tumor-adjacent breast tissue contains altered fibroblasts that diminish normal progenitor proliferation while augmenting breast cancer cell growth.
Swaroop and colleagues demonstrate that rotating-wall vessel bioreactor culture provides a favorable environment for improved growth and differentiation of retinal organoids, closely recapitulating early stages of development in vivo.