MilliporeSigma
  • Phagocytosing differentiated cell-fragments is a novel mechanism for controlling somatic stem cell differentiation within a short time frame.

Phagocytosing differentiated cell-fragments is a novel mechanism for controlling somatic stem cell differentiation within a short time frame.

Cellular and molecular life sciences : CMLS (2022-10-07)
Shohei Wakao, Yo Oguma, Yoshihiro Kushida, Yasumasa Kuroda, Kazuki Tatsumi, Mari Dezawa
ABSTRACT

Stem cells undergo cytokine-driven differentiation, but this process often takes longer than several weeks to complete. A novel mechanism for somatic stem cell differentiation via phagocytosing 'model cells' (apoptotic differentiated cells) was found to require only a short time frame. Pluripotent-like Muse cells, multipotent mesenchymal stem cells (MSCs), and neural stem cells (NSCs) phagocytosed apoptotic differentiated cells via different phagocytic receptor subsets than macrophages. The phagocytosed-differentiated cell-derived contents (e.g., transcription factors) were quickly released into the cytoplasm, translocated into the nucleus, and bound to promoter regions of the stem cell genomes. Within 24 ~ 36 h, the cells expressed lineage-specific markers corresponding to the phagocytosed-differentiated cells, both in vitro and in vivo. At 1 week, the gene expression profiles were similar to those of the authentic differentiated cells and expressed functional markers. Differentiation was limited to the inherent potential of each cell line: triploblastic-, adipogenic-/chondrogenic-, and neural-lineages in Muse cells, MSCs, and NSCs, respectively. Disruption of phagocytosis, either by phagocytic receptor inhibition via small interfering RNA or annexin V treatment, impeded differentiation in vitro and in vivo. Together, our findings uncovered a simple mechanism by which differentiation-directing factors are directly transferred to somatic stem cells by phagocytosing apoptotic differentiated cells to trigger their rapid differentiation into the target cell lineage.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Lectin from Triticum vulgaris (wheat), agarose conjugate, saline suspension
Sigma-Aldrich
Endothelin 1, ≥97% (HPLC), powder
Sigma-Aldrich
Anti-ATH 1 Antibody, Chemicon®, from rabbit
Sigma-Aldrich
Antimycin A from Streptomyces sp.
Sigma-Aldrich
Rotenone, ≥95%
Sigma-Aldrich
Hyaluronidase from bovine testes, Type I-S, lyophilized powder, 400-1000 units/mg solid
Sigma-Aldrich
Anti-Nestin Antibody, clone 10C2, clone 10C2, Chemicon®, from mouse
Sigma-Aldrich
Anti-Neurofilament M (145 kDa) Antibody, CT, serum, Chemicon®
Sigma-Aldrich
Anti-Sox9 Antibody, Chemicon®, from rabbit
Sigma-Aldrich
Anti-Troponin I Antibody, a.a. 186-192, clone C5, clone C5, Chemicon®, from mouse