title: Cell fusion reprogramming leads to a specific hepatic expression pattern during mouse bone marrow derived hepatocyte formation in vivo.
abstract: The fusion of bone marrow (BM) hematopoietic cells with hepatocytes to generate BM derived hepatocytes (BMDH) is a natural process, which is enhanced in damaged tissues. However, the reprogramming needed to generate BMDH and the identity of the resultant cells is essentially unknown. In a mouse model of chronic liver damage, here we identify a modification in the chromatin structure of the hematopoietic nucleus during BMDH formation, accompanied by the loss of the key hematopoietic transcription factor PU.1/Sfpi1 (SFFV proviral integration 1) and gain of the key hepatic transcriptional regulator HNF-1A homeobox A (HNF-1A/Hnf1a). Through genome-wide expression analysis of laser captured BMDH, a differential gene expression pattern was detected and the chromatin changes observed were confirmed at the level of chromatin regulator genes. Similarly, Tranforming Growth Factor-β1 (TGF-β(1)) and neurotransmitter (e.g. Prostaglandin E Receptor 4 [Ptger4]) pathway genes were over-expressed. In summary, in vivo BMDH generation is a process in which the hematopoietic cell nucleus changes its identity and acquires hepatic features. These BMDHs have their own cell identity characterized by an expression pattern different from hematopoietic cells or hepatocytes. The role of these BMDHs in the liver requires further investigation.
authors.affiliation: Differentiation and Cytometry Unit, Hematopoiesis and Gene Therapy Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas-CIEMAT and Centro de Investigación Biomédica en Red de Enfermedades Raras-CIBER-ER, Madrid, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Quintana-Bustamante
authors.forename: Esther
authors.initials: E
authors.lastname: Grueso
authors.forename: Ramon
authors.initials: R
authors.lastname: Garcia-Escudero
authors.forename: Elvira
authors.initials: E
authors.lastname: Arza
authors.forename: Alberto
authors.initials: A
authors.lastname: Alvarez-Barrientos
authors.forename: Isabel
authors.initials: I
authors.lastname: Fabregat
authors.forename: Maria
authors.initials: M
authors.lastname: Garcia-Bravo
authors.forename: Nestor W
authors.initials: NW
authors.lastname: Meza
authors.forename: Jose C
authors.initials: JC
authors.lastname: Segovia
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002459:Cell Fusion; D002467:Cell Nucleus / Q000378:metabolism; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000166:cytology*; D006570:Heterochromatin / Q000378:metabolism; D017403:In Situ Hybridization; D051379:Mice
chemical_list: D006570:Heterochromatin