The polycomb group protein L3MBTL1 represses a SMAD5-mediated hematopoietic transcriptional program in human pluripotent stem cells.
Bottom Line: Indeed, knockdown of L3MBTL1 promotes the development of hematopoiesis and impairs neural cell fate in human pluripotent stem cells.We also found a role for L3MBTL1 in regulating SMAD5 target gene expression in mature hematopoietic cell populations, thereby affecting erythroid differentiation.Taken together, we have identified epigenetic priming of hematopoietic-specific transcriptional networks, which may assist in the development of therapeutic approaches for patients with anemia.
Affiliation: Molecular Pharmacology and Chemistry Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: email@example.com.Show MeSH
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Mentions: To assess the neural differentiation potential of the L3MBTL1-KD cells, we generated EBs and cultured them in BDNF-containing conditions that support the development of neural progenitor cells (Figure 2A, top). While control EBs developed into Nestin+ neural precursors and Tuj1+ differentiated neurons, L3MBTL1-KD cells showed impaired neural lineage differentiation (Figure 2A, bottom and right). The impaired generation of neural precursors is not dependent on decreased cell proliferation or increased apoptosis, as we found no significant change in the expression of Ki-67 and Annexin V (Figures S2A and S2B).
Affiliation: Molecular Pharmacology and Chemistry Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: firstname.lastname@example.org.