title: Generation of multipotent early lymphoid progenitors from human embryonic stem cells.
abstract: During human embryonic stem cell (ESC) hematopoietic differentiation, the description of the initial steps of lymphopoiesis remains elusive. Using a two-step culture procedure, we identified two original populations of ESC-derived hematopoietic progenitor cells (HPCs) with CD34(+)CD45RA(+)CD7(-) and CD34(+)CD45RA(+)CD7(+) phenotypes. Bulk cultures and limiting dilution assays, culture with MS5 cells in the presence of Notch ligand Delta-like-1 (DL-1), and ex vivo colonization tests using fetal thymic organ cultures showed that although CD34(+)CD45RA(+)CD7(-) HPCs could generate cells of the three lymphoid lineages, their potential was skewed toward the B cell lineages. In contrast, CD34(+)CD45RA(+)CD7(+) HPCs predominantly exhibited a T/natural killer (NK) cell differentiation potential. Furthermore these cells could differentiate equivalently into cells of the granulo-macrophagic lineage and dendritic cells and lacked erythroid potential. Expression profiling of 18 markers by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed that CD34(+)CD45RA(+)CD7(-) and CD34(+)CD45RA(+)CD7(+) HPCs express genes of the lymphoid specification and that CD34(+)CD45RA(+)CD7(-) cells express B-cell-associated genes, while CD34(+)CD45RA(+)CD7(+) HPCs display a T-cell molecular profile. Altogether, these findings indicate that CD34(+)CD45RA(+)CD7(-) and CD34(+)CD45RA(+)CD7(+) HPCs correspond to candidate multipotent early lymphoid progenitors polarized toward either the B or T/NK lineage, respectively. This work should improve our understanding of the early steps of lymphopoiesis from pluripotent stem cells and pave the way for the production of lymphocytes for cell-based immunotherapy and lymphoid development studies.
authors: 1 Inserm UMR 935, "ESTeam Paris Sud", Stem Cell Core Facility SFR André Lwoff, Paul Brousse Hospital, University Paris Sud , Villejuif, France .
authors: Aniya
authors: A
authors: Larbi
authors: Maria Teresa
authors: MT
authors: Mitjavila-Garcia
authors: Stéphane
authors: S
authors: Flamant
authors: Yannick
authors: Y
authors: Valogne
authors: Denis
authors: D
authors: Clay
authors: Benoît
authors: B
authors: Usunier
authors: Bruno
authors: B
authors: l'Homme
authors: Olivier
authors: O
authors: Féraud
authors: Ibrahim
authors: I
authors: Casal
authors: Emilie
authors: E
authors: Gobbo
authors: Dominique
authors: D
authors: Divers
authors: Alain
authors: A
authors: Chapel
authors: Ali G
authors: AG
authors: Turhan
authors: Annelise
authors: A
authors: Bennaceur-Griscelli
authors: Rima
authors: R
authors: Haddad
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002460:Cell Line; D019070:Cell Lineage; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006410:Hematopoiesis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D054503:Lymphoid Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins