Transdifferentiation is a complete and stable change in cell identity that serves as an alternative to stem-cell-mediated organ regeneration. In adult mammals, findings of transdifferentiation have been limited to the replenishment of cells lost from preexisting structures, in the presence of a fully developed scaffold and niche1. Here we show that transdifferentiation of hepatocytes in the mouse liver can build a structure that failed to form in development-the biliary system in a mouse model t ...[more]
Project description:We observed de novo formation of peripheral bile ducts by transdifferentiation of hepatocytes in mice born without peripheral bile ducts. To assess the authenticity and maturity of the hepatocyte-derived peripheral cholangiocytes forming the new bile ducts, we compared their global gene expression profile to that of peripheral cholangiocytes isolated from normal mice. We also included hepatocytes isolated from mice born without peripheral bile ducts as a control. Overall design: We isolated hepatocyte-derived peripheral cholangiocytes, peripheral cholangiocytes and hepatocytes from mouse livers by FACS, extracted RNA and performed RNA-seq, using single end 50bp reads.
Project description:Exogenous overexpression of CEBPA transcription factor induces transdifferentiation from pro B cells into functional macrophages. Here we report the CEBPA binding ChIP-Seq data at 12 hours time point after induction of transdifferentiation in human BLaER1 cells (Rapino et al. 2013).
Project description:We previously showed that severe liver diseases are characterized by expansion of liver progenitor cells (LPC), which correlates with disease severity. However, the origin and role of LPC in liver physiology and in the hepatic response to injury remains a contentious topic. We have now used genetic lineage tracing of Hnf1β-expressing biliary duct cells to assess their contribution to LPC expansion and hepatocyte generation during normal liver homeostasis, and following different types of liver injury. We found that ductular reaction cells in human cirrhotic livers express HNF1β. However, HNF1β expression was not present in newly generated EpCAM-positive hepatocytes. Using a tamoxifen-inducible Hnf1βCreER/R26RYFP/LacZ mouse, we show that there is no contribution of the biliary epithelium to hepatocyte turnover during liver homeostasis in healthy mice. Moreover, after loss of liver mass, Hnf1β+ LPC did not contribute to hepatocyte regeneration. We also assessed the contribution of Hnf1β+ cells following acute and repeated liver injury. All animal models showed expansion of LPC, as assessed by immunostaining and gene expression profile of sorted YFP-positive cells. A contribution of Hnf1β+ LPC to hepatocyte generation was not detected in animal models of liver injury with preserved hepatocyte regenerative potential such as acute acetaminophen, carbon tetrachloride injury, or chronic diethoxycarbonyl-1,4-dihydro-collidin (DDC)-diet. However, in mice fed with choline-deficient ethionine-supplemented (CDE)-diet, which causes profound hepatocyte damage and arrest, a small number of hepatocytes were derived from Hnf1β+ cells. Conclusion: Hnf1β+ cells do not participate in hepatocyte turnover in the healthy liver or during liver regeneration after partial hepatectomy. After liver injury, LPC arise from the biliary duct epithelium, which gives rise to a limited number of hepatocytes only when hepatocyte regeneration is compromised. Transcriptomic profile using MoGeneST-2.0 chip from 3 samples of YFP+ CDE, 3 samples of YFP+ DDC, 2 samples of YFP+ UTR and 3 samples YFP-
Project description:Collombet2016 - Lymphoid and myeloid cell
specification and transdifferentiation
This model is described in the article:
Logical modeling of lymphoid
and myeloid cell specification and transdifferentiation
Samuel Collombet, Chris van Oevelen,
Jose Luis Sardina Ortega, Wassim Abou-Jaoudé, Bruno Di
Stefano, Morgane Thomas-Chollier, Thomas Graf, and Denis
Proceedings of the National Academy of
Sciences of the United States of America
Blood cells are derived from a common set of hematopoietic
stem cells, which differentiate into more specific progenitors
of the myeloid and lymphoid lineages, ultimately leading to
differentiated cells. This developmental process is controlled
by a complex regulatory network involving cytokines and their
receptors, transcription factors, and chromatin remodelers.
Using public data and data from our own molecular genetic
experiments (quantitative PCR, Western blot, EMSA) or
genome-wide assays (RNA-sequencing, ChIP-sequencing), we have
assembled a comprehensive regulatory network encompassing the
main transcription factors and signaling components involved in
myeloid and lymphoid development. Focusing on B-cell and
macrophage development, we defined a qualitative dynamical
model recapitulating cytokine-induced differentiation of common
progenitors, the effect of various reported gene knockdowns,
and the reprogramming of pre-B cells into macrophages induced
by the ectopic expression of specific transcription factors.
The resulting network model can be used as a template for the
integration of new hematopoietic differentiation and
transdifferentiation data to foster our understanding of
lymphoid/myeloid cell-fate decisions.
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Project description:au10-15_cineroots - transdifferentiation - Study of the molecular mechanism during transdifferenciation from root apical meristem to shoot apical meristem - culture in middle with different hormons, permits transdifferenciation from root to shoot tissues. 6 dye-swap - time course