Role of CD133 in human embryonic stem cell proliferation and teratoma formation

Abstract

Background: Pluripotent stem cells (PSCs), including human embryonic stem cells (hESCs), hold great potential for regenerative medicine and cell therapy. One of the major hurdles hindering the clinical development of PSC-based therapy is the potential risk of tumorigenesis. CD133 (Prominin 1, PROM1) is a transmembrane protein whose mRNA and glycosylated forms are highly expressed in many human cancer cell types. CD133 also serves as a cancer stem cell (CSC) marker associated with cancer progression and patient outcome. Interestingly, CD133 is highly expressed in hESCs as well as in human preimplantation embryos, but its function in hESCs has remained largely unknown. Methods: CD133 knockout hESC WA26 cell line was generated with CRISPR/Cas9. CD133 knockout and wide type hESC lines were subjected to pluripotency, proliferation, telomere biology, and teratoma tests; the related global changes and underlying mechanisms were further systemically analyzed by RNA-seq. Results: CD133 deficiency did not affect hESC pluripotency or in vivo differentiation into three germ layers but significantly decreased cell proliferation. RNA-seq revealed that CD133 deficiency dysregulated the p53, PI3K-Akt, AMPK, and Wnt signaling pathways. Alterations in these pathways have been implicated in tumor proliferation and apoptotic escape. Conclusions: Our data imply that CD133 could be an additional target and used as a selective marker to sort and eliminate undifferentiated cells in reducing potential teratoma formation risk of hESCs in regenerative medicine.

Association of Polygenetic Risk Scores Related to Cell Differentiation and Inflammation with Thyroid Cancer Risk and Genetic Interaction with Dietary Intake

“…Several studies have reported that NRG1 is a predisposition to papillary thyroid cancer, but no genetic variant of NRG1 has been reported about the association with the thyroid cancer risk [ 13 , 25 ]. PROM1 , also known as CD133, is a pentaspan transmembrane glycoprotein that promotes tumor initiation by thyroid cancer stem cells and suppresses cancer cells’ differentiation and helps maintain stem cell properties [ 26 ]. LRP1B is an endocytic receptor that acts as a tumor suppressor by constraining the invasive behaviors of thyroid cancer and other cancer cells [ 27 ].…”

Benzimidazole based derivatives as anticancer agents: Structure activity relationship analysis for various targets

“…Various human cancer cell types express mRNA and glycosylated forms of CD113. It also acts as a CSC (cancer stem cell) marker and hence plays pivotal role in induction of inflammation, tumor initiation, progression, invasion, and metastasis [139–141].…”

Recent trends in stem cell-based therapies and applications of artificial intelligence in regenerative medicine

“…Still, the proliferating potential is reduced and results in reduced teratoma formation[ 51 ]. Therefore, CD133 may be used to sort ESCs for transplantation[ 52 ].…”