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What’s the Stem Cells Buzz this Week? - PARP Inhibition and Chemosensitivity, Xist Intron 1 in Reprogramming, BIN1 and hESC-CMs, and lncHOXC-AS3 in Osteogenesis!



The Stem Cells Portal brings you a roundup of some of the new and exciting stories in the ever-changing world of stem cells, regenerative medicine, and beyond!

PARP Inhibition and Chemosensitivity in Colorectal Cancer‐initiating Cells

Cancer‐initiating cells (CICs) contribute to the relapse of colon tumorigenesis, a leading killer in the US that suffers from resistance to treatments. In a new STEM CELLS study, researchers from the labs of Matthew F. Kalady (Case Western Reserve University, Cleveland, Ohio, USA) and Jeremy N Rich (University California, San Diego, California, USA) report that patient‐derived CICs display relative chemoresistance compared to differentiated progeny, although conventional cell lines failed to model therapeutic resistance. However, Jarrar et al. discovered that inhibition of poly‐ADP‐ribose polymerase (PARP), a critical single‐strand break repair mediator, sensitized CICs to chemotherapy, suggesting that a novel combinatorial strategy may serve as an effective means to treat colon cancer.

The Role of Xist Intron 1 in Somatic Cell Reprogramming

A recent STEM CELLS study from the labs of Pentao Liu (Wellcome Trust Sanger Institute, Cambridge, UK) and Xihe Li (Inner Mongolia University, Hohhot, China) sought to understand the role of Xist, the master regulator of X chromosome inactivation (XCI), in the reprogramming process through the activity of transcription‐factor‐like effectors (TALE)‐based designer transcriptional factors (dTFs). Zhang et al. discovered that binding of a repressive dTF to intron 1 of Xist in somatic cells did not affect Xist expression; however, the epigenetic perturbations led to substantial improvements in induced pluripotent stem cell generation and somatic cell nuclear transfer preimplantation embryo development. The authors anticipate that their findings may provide a unique route to reprogramming.

BIN1 promotes Generation of hESC-Cardiomyocytes with Ventricular Phenotype

The production of mature cardiomyocytes from human embryonic stem cells (hESC-CMs) will impact both cell therapies for cardiac disease and disease modeling. Now, researchers from the labs of Claudia M. Moreno and Luis Fernando Santana (University of California, Davis, California, USA) have revealed that the expression of Bridging Integrator 1 (BIN1) facilitates the production of mature ventricular-like cardiomyocytes by regulating the formation of T-tubules and adult-like Ca2+ release units. De la Mata et al. hope that this new advance will generate cells better suited to both regenerative therapy and modeling. See STEM CELLSnow to discover more!

Role of lncHOXC-AS3 in MSC Osteogenesis

Mesenchymal stem cells (MSCs) derived from multiple myeloma (MM) patients display impaired osteogenic differentiation, although the molecular mechanisms involved remain unknown. Now, a new STEM CELLS study led by Wenzhuo Zhuang and Yongsheng Zhang (Soochow University, Suzhou, China) has established that MM‐MSCs specifically overexpress the bioactive lncRNA HOXC‐AS3, which interacts with HOXC10, increases HOXC10 stability, and promotes HOXC10 expression, thereby repressing osteogenesis in MM‐MSCs. Li et al. hope that their study demonstrates the potential clinical significance of lncRNA HOXC‐AS3 as a therapeutic target for bone disease in MM.

That’s a wrap for now! Please feel free to leave a comment and discuss the papers covered here on the Stem Cells Buzz. Happy reading!