title: Identification of key regulatory pathways of myeloid differentiation using an mESC-based karyotypically normal cell model.
abstract: Understanding the process of myeloid differentiation offers important insights into both normal and abnormal developmental processes but is limited by the dearth of experimental models. Here we show that myeloid progenitors can be derived from embryonic stem cells, immortalized, and applied to the study of the mechanisms underlying myeloid differentiation. The embryonic stem cell-derived myeloid progenitors, when immortalized with estrogen-regulated Hoxb8 protein, demonstrate normal karyotyping, are genetically tractable, and can be differentiated into functional neutrophils. Using this model, we identified mammalian target of rapamycin complex 1 as a critical regulator of myeloid differentiation. Together, our studies led to a convenient, karyotypically normal, and genetically manipulatable cellular system, which can be used to shed new light on the mechanisms for myeloid differentiation.
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. dongly@uiuc.edu
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Hong
authors.initials: H
authors.lastname: Nan
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Sulei
authors.initials: S
authors.lastname: Pang
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.forename: Rotem
authors.initials: R
authors.lastname: Karni
authors.forename: Mark P
authors.initials: MP
authors.lastname: Kamps
authors.forename: Yuanfu
authors.initials: Y
authors.lastname: Xu
authors.forename: Jiaxi
authors.initials: J
authors.lastname: Zhou
authors.forename: Therese
authors.initials: T
authors.lastname: Wiedmer
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sims
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D059785:Karyotype; D051379:Mice; D008810:Mice, Inbred C57BL; D023461:Myeloid Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C095822:Hoxb8 protein, mouse; D016179:Granulocyte Colony-Stimulating Factor; D004958:Estradiol; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus