title: Molecular signature of erythroblast enucleation in human embryonic stem cells.
abstract: While enucleation is a critical step in the terminal differentiation of human red blood cells, the molecular mechanisms underlying this unique process remain unclear. To investigate erythroblast enucleation, we studied the erythroid differentiation of human embryonic stem cells (hESCs), which provide a unique model for deeper understanding of the development and differentiation of multiple cell types. First, using a two-step protocol, we demonstrated that terminal erythroid differentiation from hESCs is directly dependent on the age of the embryoid bodies. Second, by choosing hESCs in two extreme conditions of erythroid culture, we obtained an original differentiation model which allows one to study the mechanisms underlying the enucleation of erythroid cells by analyzing the gene and miRNA (miR) expression profiles of cells from these two culture conditions. Third, using an integrated analysis of mRNA and miR expression profiles, we identified five miRs potentially involved in erythroblast enucleation. Finally, by selective knockdown of these five miRs we found miR-30a to be a regulator of erythroblast enucleation in hESCs.
authors: UPMC Univ Paris 06, UMR_S938 CDR Saint-Antoine, Prolifération et Différentiation des Cellules Souches, Paris, France.|INSERM, UMR_S938, Prolifération et Différentiation des Cellules Souches, Paris, France.|Laboratory of Excellence GR-Ex, Paris, France.
authors: Shaghayegh
authors: S
authors: Rouzbeh
authors: UPMC Univ Paris 06, UMR_S938 CDR Saint-Antoine, Prolifération et Différentiation des Cellules Souches, Paris, France.|INSERM, UMR_S938, Prolifération et Différentiation des Cellules Souches, Paris, France.|Laboratory of Excellence GR-Ex, Paris, France.
authors: Ladan
authors: L
authors: Kobari
authors: Institut National de Transfusion Sanguine INTS, Paris, France.
authors: Marie
authors: M
authors: Cambot
authors: UPMC Univ Paris 06, UMR_S938 CDR Saint-Antoine, Prolifération et Différentiation des Cellules Souches, Paris, France.|INSERM, UMR_S938, Prolifération et Différentiation des Cellules Souches, Paris, France.|Laboratory of Excellence GR-Ex, Paris, France.|EFS Ile de France, Unité d'Ingénierie et de Thérapie Cellulaire, Créteil, France.
authors: Christelle
authors: C
authors: Mazurier
authors: UPMC Univ Paris 06, UMR_S938 CDR Saint-Antoine, Prolifération et Différentiation des Cellules Souches, Paris, France.|INSERM, UMR_S938, Prolifération et Différentiation des Cellules Souches, Paris, France.|Laboratory of Excellence GR-Ex, Paris, France.|EFS Ile de France, Unité d'Ingénierie et de Thérapie Cellulaire, Créteil, France.
authors: Nicolas
authors: N
authors: Hebert
authors: IFR 65-Saint Antoine UMPC, Plateforme de Cytométrie, Paris, France.
authors: Anne-Marie
authors: AM
authors: Faussat
authors: CNRS UMR7622, Laboratoire de biologie et du développement, Paris, France.|UPMC UMR7622, Laboratoire de biologie et du développement, Paris, France.
authors: Charles
authors: C
authors: Durand
authors: UPMC Univ Paris 06, UMR_S938 CDR Saint-Antoine, Prolifération et Différentiation des Cellules Souches, Paris, France.|INSERM, UMR_S938, Prolifération et Différentiation des Cellules Souches, Paris, France.|Laboratory of Excellence GR-Ex, Paris, France.|EFS Ile de France, Unité d'Ingénierie et de Thérapie Cellulaire, Créteil, France.|AP-HP, Hôpital St Antoine et Hôpital Trousseau, Service d'Hématologie et Immunologie Biologiques, Paris, France.
authors: Luc
authors: L
authors: Douay
authors: UPMC Univ Paris 06, UMR_S938 CDR Saint-Antoine, Prolifération et Différentiation des Cellules Souches, Paris, France.|INSERM, UMR_S938, Prolifération et Différentiation des Cellules Souches, Paris, France.|Laboratory of Excellence GR-Ex, Paris, France.|AP-HP, Hôpital St Antoine et Hôpital Trousseau, Service d'Hématologie et Immunologie Biologiques, Paris, France.
authors: Hélène
authors: H
authors: Lapillonne
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D004900:Erythroblasts / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: Embryonic stem cells; Enucleation; Erythropoiesis; MiR-30a