Discovery of a Small-Molecule BMP Sensitizer for Human Embryonic Stem Cell Differentiation

Feng, Lingling; Cook, Brandoch D.; Tsai, Su-Yi; Zhou, Ting; LaFlamme, Brooke; Evans, Todd; Chen, Shuibing

doi:10.1016/j.celrep.2016.04.066

Cited by 24 publications

(37 citation statements)

References 51 publications

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“…Among those, importazole is a transport receptor importin-β ( 47 ) and AG 957 is a protein tyrosine kinase inhibitor ( 48 ). Moreover, brazilin is a NF-kappaB inhibitor ( 49 ) and PD 407824, a hepatoprotective agent, is known as Wee1/Chk1 inhibitor ( 50 ), whereas Ro 28-1675 is known as glucokinase activator ( 51 ). However, the action mechanisms of NCGC00182353-01 and NCGC00181381-01 were not identified yet ( Supplementary Table 5 ).…”

Section: Resultsmentioning

confidence: 99%

Drug Repositioning for P-Glycoprotein Mediated Co-Expression Networks in Colorectal Cancer

et al. 2020

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Colorectal cancer (CRC) is one of the most fatal types of cancers that is seen in both men and women. CRC is the third most common type of cancer worldwide. Over the years, several drugs are developed for the treatment of CRC; however, patients with advanced CRC can be resistant to some drugs. P-glycoprotein (P-gp) (also known as Multidrug Resistance 1, MDR1) is a well-identified membrane transporter protein expressed by ABCB1 gene. The high expression of MDR1 protein found in several cancer types causes chemotherapy failure owing to efflux drug molecules out of the cancer cell, decreases the drug concentration, and causes drug resistance. As same as other cancers, drug-resistant CRC is one of the major obstacles for effective therapy and novel therapeutic strategies are urgently needed. Network-based approaches can be used to determine specific biomarkers, potential drug targets, or repurposing approved drugs in drug-resistant cancers. Drug repositioning is the approach for using existing drugs for a new therapeutic purpose; it is a highly efficient and low-cost process. To improve current understanding of the MDR-1-related drug resistance in CRC, we explored gene co-expression networks around ABCB1 gene with different network sizes (50, 100, 150, 200 edges) and repurposed candidate drugs targeting the ABCB1 gene and its co-expression network by using drug repositioning approach for the treatment of CRC. The candidate drugs were also assessed by using molecular docking for determining the potential of physical interactions between the drug and MDR1 protein as a drug target. We also evaluated these four networks whether they are diagnostic or prognostic features in CRC besides biological function determined by functional enrichment analysis. Lastly, differentially expressed genes of drug-resistant (i.e., oxaliplatin, methotrexate, SN38) HT29 cell lines were found and used for repurposing drugs with reversal gene expressions. As a result, it is shown that all networks exhibited high diagnostic and prognostic performance besides the identification of various drug candidates for drug-resistant patients with CRC. All these results can shed light on the development of effective diagnosis, prognosis, and treatment strategies for drug resistance in CRC.

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Section: Resultsmentioning

confidence: 99%

Drug Repositioning for P-Glycoprotein Mediated Co-Expression Networks in Colorectal Cancer

et al. 2020

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“…4b), there is a difference with the non-canonical BMP4/TGF-B pathway. Though required to maintain pluripotency in mESC, BMP4 signalling promotes differentiation of primed PSCs 47 . Our data show increased expression in the ‘High’ Pluritest category of calcineurin, which is the catalytic subunit gamma of PP3 (Fig.…”

Section: Resultsmentioning

confidence: 99%

The iPSC proteomic compendium

Brenes

Bensaddek

Hukelmann

et al. 2018

Preprint

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Induced pluripotent stem cell (iPSC) technology holds great potential for therapeutic and research purposes. The Human Induced Pluripotent Stem Cell Initiative (HipSci) was established to generate a panel of high-quality iPSCs, from healthy and disease cohorts, with accompanying multi-omics and phenotypic data. Here, we present a proteomic analysis of 217 HipSci iPSC lines obtained from 163 donors.This dataset provides a comprehensive proteomic map of iPSCs, identifying >16,000 protein groups. We analyse how the expression profiles of proteins involved in cell cycle, metabolism and DNA repair contribute to key features of iPSC biology and we identify potential new regulators of the primed pluripotent state. To facilitate access, all these data have been integrated into the Encyclopedia of Proteome Dynamics (www.peptracker.com/epd), where it can be browsed interactively. Additionally, we generated an iPSC specific spectral library for DIA which we deposited in PRIDE along with the raw and processed mass-spectrometry data.

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“…Myoblasts are derived from mesenchymal-derived precursors [38]. It has been reported that C2C12 myoblasts are reprogrammed into mature osteoblasts by the stimulation with bone morphogenetic proteins (BMPs) as BMP-2 and BMP-4 [39,40]. The common mesenchymal origin of L8 with the former cell lines possibly explains the detection of A7 antigen in L8 cells.…”

Section: Discussionmentioning

confidence: 99%

Osteoblast lineage-specific cell-surface antigen (A7) regulates osteoclast recruitment and calcification during bone remodeling

Badawy

Kyumoto‐Nakamura

Uehara

et al. 2019

Laboratory Investigation

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Bone remodeling is a continuous process characterized by highly coordinated cell-cell interactions in distinct multi-cellular units. Osteoclasts, which are specialized bone resorbing cells, play a central role in bone remodeling. Although the RANKL/ RANK axis determines the gross number of osteoclasts present in bone tissue, detailed molecular events regulating bone remodeling related to osteoclast recruitment, initiation of bone remodeling, and coupling of bone resorption and bone formation are still ambiguous. We hypothesized that osteoblast-specific cell-surface molecules contribute to the molecular modulation of bone remodeling. Therefore, we searched for regulatory cell-surface molecules expressed on osteoblasts by use of B-cell hybridoma technology. We obtained a monoclonal antibody A7 (A7 MAb) highly specific to cells of osteoblast-lineage. Here we describe the expression pattern and possible role of A7 antigen specifically recognized by A7 MAb. In vitro, A7 antigen was expressed on cell-surface of osteoblasts and osteoblast-like bone marrow stromal cells. In vivo, A7 antigen was detected in a subset of bone surface osteoblasts and in osteocytes, with a typical cell membrane expression pattern. Tissue array analysis showed only a limited expression of A7 antigen in osteocytes close to the bone surface. Immunoblotting and immunoprecipitation analysis showed that A7 antigen is a lineage-specific cell-surface protein with an approximate molecular weight of 45 KDa. Cross-linking of cell-surface A7 antigen in cultures of osteoclastogenesis showed stimulation of osteoclast formation. Marked suppression of calcification in primary osteoblast cultures was observed when A7 antigen was cross-linked with anti-A7 antigen MAb, A7 MAb. These data suggest that A7 antigen regulates recruitment of osteoclasts and triggering of calcification. A7 antigen may be an important molecule involved in the precise regulation of bone remodeling.

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Discovery of a Small-Molecule BMP Sensitizer for Human Embryonic Stem Cell Differentiation

Cited by 24 publications

References 51 publications

Drug Repositioning for P-Glycoprotein Mediated Co-Expression Networks in Colorectal Cancer

Drug Repositioning for P-Glycoprotein Mediated Co-Expression Networks in Colorectal Cancer

The iPSC proteomic compendium

Osteoblast lineage-specific cell-surface antigen (A7) regulates osteoclast recruitment and calcification during bone remodeling

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