---
title: "Polyampholyte hydrogel induces cancer stem cell signatures in colorectal cancer cells"
id: "pubmed-42537436"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42537436"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42537436/"
doi: "10.1016/j.bbrc.2026.154359"
published_at: "2026-09-24T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Polyampholyte hydrogel induces cancer stem cell signatures in colorectal cancer cells
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42537436
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42537436/)
- **DOI:** [10.1016/j.bbrc.2026.154359](https://doi.org/10.1016%2Fj.bbrc.2026.154359)
- **Published At:** 2026-09-24T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Colorectal cancer (CRC) remains prevalent and lethal; targeting **cancer stem cells (CSCs)** is essential for improved therapies. - The study reports that cultivation of conventional CRC cell lines on a **synthetic hydrogel scaffold** reprograms them toward a CSC-like state. - A **polyampholyte hydrogel** with a net positive charge specifically enhanced expression of multiple stem cell markers in CRC cells. - Whole transcriptome analysis showed global upregulation of signatures related to **CSC** and intestinal stem cells when cells were cultured on the hydrogel. - Transcriptomic reprogramming was accompanied by a metabolic shift in CRC cells from glycolysis toward **oxidative phosphorylation**. - The transcription factor **MEF2D** was identified as a key regulator that promotes the CSC signature in CRC under hydrogel culture. - The authors propose the hydrogel culture system as a versatile in vitro platform to induce CSC traits and to probe mechanisms that support CSC biology in CRC. - Conflict of interest: the authors declared no known competing financial interests or personal relationships influencing the work. - Details on experimental protocols, specific cell lines, quantified marker changes, and additional mechanistic validation were not reported in the abstract and would require consulting the full text for complete methodological data.
## Clinical Analysis & Structured Key Points
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Epub 2026 Jul 29. # A synthetic hydrogel scaffold enhancing stem cell signatures in colorectal cancer cells [Qiaochu Fu](https://pubmed.ncbi.nlm.nih.gov/?term=Fu+Q&cauthor_id=42537436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42537436/#full-view-affiliation-1 "Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, N15, W7, Kita-ku, Sapporo, 060-8638, Japan; Institute for Chemical Reaction Design and Discovery \(WPI-ICReDD\), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan."), [Cewen Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+C&cauthor_id=42537436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42537436/#full-view-affiliation-1 "Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, N15, W7, Kita-ku, Sapporo, 060-8638, Japan; Institute for Chemical Reaction Design and Discovery \(WPI-ICReDD\), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan."), [Lei Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+L&cauthor_id=42537436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42537436/#full-view-affiliation-1 "Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, N15, W7, Kita-ku, Sapporo, 060-8638, Japan; Institute for Chemical Reaction Design and Discovery \(WPI-ICReDD\), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan."), [Takayuki Nonoyama](https://pubmed.ncbi.nlm.nih.gov/?term=Nonoyama+T&cauthor_id=42537436)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42537436/#full-view-affiliation-2 "Faculty of Advanced Life Science, Hokkaido University, N21, W11, Kita-ku, Sapporo, 001-0021, Japan; Co-Creation Core for Soft Materials Aspiring Research & Translation \(C3-SMART\), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan."), [Jian Ping Gong](https://pubmed.ncbi.nlm.nih.gov/?term=Gong+JP&cauthor_id=42537436)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42537436/#full-view-affiliation-3 "Institute for Chemical Reaction Design and Discovery \(WPI-ICReDD\), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan; Faculty of Advanced Life Science, Hokkaido University, N21, W11, Kita-ku, Sapporo, 001-0021, Japan; Co-Creation Core for Soft Materials Aspiring Research & Translation \(C3-SMART\), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan."), [Shinya Tanaka](https://pubmed.ncbi.nlm.nih.gov/?term=Tanaka+S&cauthor_id=42537436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42537436/#full-view-affiliation-1 "Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, N15, W7, Kita-ku, Sapporo, 060-8638, Japan; Institute for Chemical Reaction Design and Discovery \(WPI-ICReDD\), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan."), [Masamichi Imajo](https://pubmed.ncbi.nlm.nih.gov/?term=Imajo+M&cauthor_id=42537436)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42537436/#full-view-affiliation-4 "Institute for Chemical Reaction Design and Discovery \(WPI-ICReDD\), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan. Electronic address: m-imajo@icredd.hokudai.ac.jp.") Affiliations Expand ### Affiliations * 1 Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, N15, W7, Kita-ku, Sapporo, 060-8638, Japan; Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan. * 2 Faculty of Advanced Life Science, Hokkaido University, N21, W11, Kita-ku, Sapporo, 001-0021, Japan; Co-Creation Core for Soft Materials Aspiring Research & Translation (C3-SMART), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan. * 3 Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan; Faculty of Advanced Life Science, Hokkaido University, N21, W11, Kita-ku, Sapporo, 001-0021, Japan; Co-Creation Core for Soft Materials Aspiring Research & Translation (C3-SMART), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan. * 4 Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan. Electronic address: m-imajo@icredd.hokudai.ac.jp. * PMID: **42537436** * DOI: [ 10.1016/j.bbrc.2026.154359 ](https://doi.org/10.1016/j.bbrc.2026.154359) Item in Clipboard # A synthetic hydrogel scaffold enhancing stem cell signatures in colorectal cancer cells Qiaochu Fu et al. Biochem Biophys Res Commun. 2026. Show details Display options Display options Format Abstract PubMed PMID Biochem Biophys Res Commun Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Biochem+Biophys+Res+Commun%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Biochem+Biophys+Res+Commun%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42537436/) . 2026 Sep 24:832:154359. doi: 10.1016/j.bbrc.2026.154359. Epub 2026 Jul 29. ### Authors [Qiaochu Fu](https://pubmed.ncbi.nlm.nih.gov/?term=Fu+Q&cauthor_id=42537436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42537436/#short-view-affiliation-1 "Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, N15, W7, Kita-ku, Sapporo, 060-8638, Japan; Institute for Chemical Reaction Design and Discovery \(WPI-ICReDD\), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan."), [Cewen Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+C&cauthor_id=42537436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42537436/#short-view-affiliation-1 "Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, N15, W7, Kita-ku, Sapporo, 060-8638, Japan; Institute for Chemical Reaction Design and Discovery \(WPI-ICReDD\), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan."), [Lei Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+L&cauthor_id=42537436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42537436/#short-view-affiliation-1 "Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, N15, W7, Kita-ku, Sapporo, 060-8638, Japan; Institute for Chemical Reaction Design and Discovery \(WPI-ICReDD\), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan."), [Takayuki Nonoyama](https://pubmed.ncbi.nlm.nih.gov/?term=Nonoyama+T&cauthor_id=42537436)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42537436/#short-view-affiliation-2 "Faculty of Advanced Life Science, Hokkaido University, N21, W11, Kita-ku, Sapporo, 001-0021, Japan; Co-Creation Core for Soft Materials Aspiring Research & Translation \(C3-SMART\), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan."), [Jian Ping Gong](https://pubmed.ncbi.nlm.nih.gov/?term=Gong+JP&cauthor_id=42537436)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42537436/#short-view-affiliation-3 "Institute for Chemical Reaction Design and Discovery \(WPI-ICReDD\), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan; Faculty of Advanced Life Science, Hokkaido University, N21, W11, Kita-ku, Sapporo, 001-0021, Japan; Co-Creation Core for Soft Materials Aspiring Research & Translation \(C3-SMART\), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan."), [Shinya Tanaka](https://pubmed.ncbi.nlm.nih.gov/?term=Tanaka+S&cauthor_id=42537436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42537436/#short-view-affiliation-1 "Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, N15, W7, Kita-ku, Sapporo, 060-8638, Japan; Institute for Chemical Reaction Design and Discovery \(WPI-ICReDD\), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan."), [Masamichi Imajo](https://pubmed.ncbi.nlm.nih.gov/?term=Imajo+M&cauthor_id=42537436)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42537436/#short-view-affiliation-4 "Institute for Chemical Reaction Design and Discovery \(WPI-ICReDD\), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan. Electronic address: m-imajo@icredd.hokudai.ac.jp.") ### Affiliations * 1 Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, N15, W7, Kita-ku, Sapporo, 060-8638, Japan; Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan. * 2 Faculty of Advanced Life Science, Hokkaido University, N21, W11, Kita-ku, Sapporo, 001-0021, Japan; Co-Creation Core for Soft Materials Aspiring Research & Translation (C3-SMART), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan. * 3 Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan; Faculty of Advanced Life Science, Hokkaido University, N21, W11, Kita-ku, Sapporo, 001-0021, Japan; Co-Creation Core for Soft Materials Aspiring Research & Translation (C3-SMART), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan. * 4 Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, N21, W10, Kita-ku, Sapporo, 001-0021, Japan. Electronic address: m-imajo@icredd.hokudai.ac.jp. * PMID: **42537436** * DOI: [ 10.1016/j.bbrc.2026.154359 ](https://doi.org/10.1016/j.bbrc.2026.154359) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Colorectal cancer (CRC) is one of the most prevalent and lethal malignancies worldwide. Strategies to eradicate cancer stem cells (CSCs) are essential for developing more promising therapies against CRC. However, the rarity and heterogeneity of these cells within tumor masses have impeded a deeper understanding of CSCs. Here, we show that cultivation on synthetic hydrogel scaffolds induces reprogramming of conventional CRC cell lines into a CSC-like state. We found that culture on a polyampholyte hydrogel with a net positive charge enhanced the expression of several stem cell markers in CRC cells. Whole transcriptome analysis revealed that signatures related to CSCs and intestinal stem cells were globally upregulated by hydrogel culture. As a result of this transcriptional reprogramming, CRC cells exhibited a metabolic shift from glycolysis to oxidative phosphorylation. Moreover, we identified MEF2D as a key transcription factor that promotes the CSC signature in CRC. Together, these results establish a hydrogel culture system as a versatile platform for inducing CSC traits in CRC cells and demonstrate its usefulness in elucidating mechanisms supporting CSCs. **Keywords:** Cancer stem cells; Colorectal cancer; MEF2; Reprogramming; Synthetic hydrogel. Copyright © 2026 Elsevier Inc. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ Hyaluronic acid hydrogels with defined crosslink density for the efficient enrichment of breast cancer stem cells. ](https://pubmed.ncbi.nlm.nih.gov/31125725/) Tan S, Yamashita A, Gao SJ, Kurisawa M.Tan S, et al.Acta Biomater. 2019 Aug;94:320-329. doi: 10.1016/j.actbio.2019.05.040. Epub 2019 May 22.Acta Biomater. 2019.PMID: 31125725 * [ Biomarker Identification via Spatial Transcriptomics Profiling of Colorectal Cancer and Colorectal Cancer with Liver Metastasis Stem Cells. ](https://pubmed.ncbi.nlm.nih.gov/41303528/) Lee M, Han S, Kim HC, Jung Y, Gim JA, Kim CJ, Jeong D.Lee M, et al.Int J Mol Sci. 2025 Nov 14;26(22):11045. doi: 10.3390/ijms262211045.Int J Mol Sci. 2025.PMID: 41303528Free PMC article. * [ Differentiated cancer cell-originated lactate promotes the self-renewal of cancer stem cells in patient-derived colorectal cancer organoids. ](https://pubmed.ncbi.nlm.nih.gov/32898601/) Zhao H, Yan C, Hu Y, Mu L, Liu S, Huang K, Li Q, Li X, Tao D, Qin J.Zhao H, et al.Cancer Lett. 2020 Nov 28;493:236-244. doi: 10.1016/j.canlet.2020.08.044. Epub 2020 Sep 6.Cancer Lett. 2020.PMID: 32898601 * [ Cancer stem cells in colorectal cancer: a review. ](https://pubmed.ncbi.nlm.nih.gov/28942428/) Munro MJ, Wickremesekera SK, Peng L, Tan ST, Itinteang T.Munro MJ, et al.J Clin Pathol. 2018 Feb;71(2):110-116. doi: 10.1136/jclinpath-2017-204739. Epub 2017 Sep 23.J Clin Pathol. 2018.PMID: 28942428Review. * [ Cell cycle heterogeneity and plasticity of colorectal cancer stem cells. ](https://pubmed.ncbi.nlm.nih.gov/38413370/) Higa T, Nakayama KI.Higa T, et al.Cancer Sci. 2024 May;115(5):1370-1377. doi: 10.1111/cas.16117. Epub 2024 Feb 27.Cancer Sci. 2024.PMID: 38413370Free PMC article.Review. [ See all similar articles ](https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from_uid=42537436) ## MeSH terms * Cell Line, Tumor Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cell+Line%2C+Tumor%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Cell+Line%2C+Tumor) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42537436/) * Cellular Reprogramming Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cellular+Reprogramming%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Cellular+Reprogramming) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42537436/) * Colorectal
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