title: CITED2 modulation of trophoblast cell differentiation: insights from global transcriptome analysis.
abstract: Trophoblast stem (TS) cells possess the capacity to differentiate along a multi-lineage pathway yielding several specialized cell types. The regulatory network controlling trophoblast cell differentiation is poorly understood. Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain, 2 (CITED2) has been implicated in the regulation of placentation; however, we know little about how CITED2 acts to influence trophoblast cells. Rat Rcho-1 TS cells can be manipulated to proliferate or differentiate into specialized trophoblast lineages and are an excellent model for investigating trophoblast differentiation. CITED2 transcript and protein showed a robust induction during Rcho-1 TS cell differentiation. We used an shRNA knockdown approach to disrupt CITED2 expression in order to investigate its involvement in trophoblast cell differentiation. RNA-sequencing was used to examine the impact of CITED2 on trophoblast cell differentiation. CITED2 disruption affected the differentiating trophoblast cell transcriptome. CITED2 possessed a prominent role in the regulation of cell differentiation with links to several signal transduction pathways and to hypoxia-regulated and coagulation processes. In summary, our findings indicate that CITED2 contributes to the regulation of trophoblast cell differentiation.
authors.affiliation: Laboratory of Theriogenology and Animal BreedingThe University of Tokyo, Bunkyo-ku, Tokyo, Japan Department of Pathology and Laboratory MedicineInstitute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA akaz@mail.ecc.u-tokyo.ac.jp msoares@kumc.edu.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Imakawa
authors.affiliation: Department of Pathology and Laboratory MedicineInstitute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
authors.forename: Pramod
authors.initials: P
authors.lastname: Dhakal
authors.affiliation: Department of Pathology and Laboratory MedicineInstitute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
authors.forename: Kaiyu
authors.initials: K
authors.lastname: Kubota
authors.affiliation: Laboratory of Theriogenology and Animal BreedingThe University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kusama
authors.affiliation: Department of Pathology and Laboratory MedicineInstitute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
authors.forename: Damayanti
authors.initials: D
authors.lastname: Chakraborty
authors.affiliation: Department of Pathology and Laboratory MedicineInstitute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Karim Rumi
authors.affiliation: Department of Pathology and Laboratory MedicineInstitute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA akaz@mail.ecc.u-tokyo.ac.jp msoares@kumc.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Soares
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C517260:CITED2 protein, rat; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors