Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transplantation-induced reprogramming determines successful hepatocyte engraftment

ABSTRACT: While demonstrated safety and efficacy in treating liver diseases, hepatocyte-based therapy faces the challenge of limited engraftment of transplanted hepatocytes (Tx-Heps) in clinical settings, akin to issues encountered in cell therapy for other solid organs. Here, we identified a conserved reprogramming state of Tx-Heps during engraftment, marked by the activation of liver progenitor genes and bipotential differentiation capacity. Transplantation reprogramming of Tx-Heps is crucial for successful engraftment, as proven by transplantation failure upon hepatocyte-specific ablation of Arid1a, which is required for Tx-Hep reprogramming. To validate translational potential, we artificially induced Tx-Hep reprogramming by in vivo treatment of either IL6 or IC7, a chimeric IL6 family protein, both of which significantly enhance hepatocyte engraftment. Our findings unveil early-stage cell fate reprogramming during transplantation and also propose a promising strategy to augment hepatocyte engraftment, which is an interesting framework to be studied in cell transplantation for other solid organs.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE275278 | GEO | 2025/08/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gene expression data of hepatocytes derived from human fibroblasts, human iPSCs, and human adult hepatocytes

Project description:Generation of human fibroblast-derived hepatocytes capable of extensive proliferation, as evidenced by significant liver repopulation of mice. Unlike current protocols for deriving hepatocytes from human fibroblasts, ours did not generate iPSCs, but shortcut reprogramming to pluripotency to generate an induced multipotent progenitor cell (iMPC) stage from which endoderm progenitor cells (iMPC-EPCs) and subsequently hepatocytes (iMPC-Heps) could be efficiently differentiated. After transplantation into an immune-deficient mouse model of human liver failure, iMPC-Heps were able to engraft and proliferate, and acquired levels of hepatocyte function similar to adult hepatocytes. Microarray analysis has been used to show: 1. post-transplant maturation in vivo of iMPC-Heps compared to aHeps, 2. differences between iMPC-Heps and freshly isolated aHeps in vitro, 3. similar profile of freshly isolated aHeps to aHeps and iMPC-Heps in vivo, and 4. similarities of expression levels of most, but not all, genes between iMPC-Heps and iPSC-Heps in vitro. We isolated repopulating nodules of iMPC-Heps and aHeps by laser-capture microscopy (LCM) around 9 months after transplantation and analyzed their gene expression on the microarray, together with RNA from in vitro samples.

2014-01-22 | E-GEOD-52309 | biostudies-arrayexpress

Gene expression patterns define the hepatocyte-like cells derived by different strategies [RNA-seq]

Project description:We performed genome-wide gene profiling in hiPSC-Hep and hiHep and compared gene expression patterns in these two types of hepatocyte-like cells.Genes involving in fat digestion and absorption and metabolism enzymes were induced in both hiHeps and hiPSC-Heps. There were also hepatic genes not expressed in either hiPSC-Heps or hiHeps, including cytochrome P450-based metabolism genes and coagulation complements. Interestingly, when genes were clustered based on their hepatic functions, we found that for each hepatic function there were always a few genes not fully induced in either hiPSC-Heps or hiHeps.

2017-11-23 | GSE103075 | GEO

ATP7B Gene Therapy of Autologous Reprogrammed Hepatocytes Alleviates Copper Accumulation in a Murine Model of Wilson’s Disease

Project description:Purpose：Wilson's disease (WD) is a rare hereditary disorder due to ATP7B gene mutation, causing pathologic copper storage mainly in the liver and neurological systems. Hepatocyte transplantation showed therapeutic potential, however, this strategy is often hindered by a shortage of quality donor cells and by allogeneic immune rejection. Here we evaluate the function and efficacy of autologous reprogrammed, ATP7B gene-restored hepatocytes using a murine model of WD Mathods and Results: By reprogramming hepatocytes from ATP7B-/- mice with small molecules, sufficient liver progenitor cells (LPCs) are harvested. After lentivirus-mediated miniATP7B gene transfection and re-differentiation, functional LPC-ATP7B-Heps are developed. RNA-seq data show that compared with LPC-GFP-Heps with enrichment of genes mainly in pathways of oxidative stress and cell apoptosis, in LPC-ATP7B-Heps under high copper stress pathways for copper ion binding and cell proliferation are enriched. LPC-ATP7B-Heps transplantation into ATP7B-/- mice alleviates deposition of excess liver copper with its associated inflammation and fibrosis, comparable to those observed using normal primary hepatocytes at four months after transplantation. Conclusion: We establish the autologous reprogrammed, ATP7B gene restored LPC-ATP7B-Heps and further transplantation demonstrate alleviated copper accumulation in WD mice.

2022-03-05 | GSE197948 | GEO

Gene expression data of hepatocytes derived from human fibroblasts, human iPSCs, and human adult hepatocytes

2014-01-22 | GSE52309 | GEO

Homo

Project description:Decellularized liver hydrogel enhances cell engraftment in orthotopic hepatocyte transplantation

| PRJDB15729 | ENA

Host senescence determines the success of hepatocyte transplantation in a mouse model of liver injury

Project description:Hepatocyte transplantation has shown promise for genetic diseases but has mixed efficacy for acute and severe liver injury. Limited cell engraftment and poor function of donor hepatocytes in recipient liver are significant hurdles for clinical efficacy. Hepatocyte senescence is a key feature of many liver diseases. Senescence-driven liver injury could be induced in Ahcre+Mdm2fl/fl mice in controlled and predictable levels through excision of hepatocyte Mdm2. Host senescence and injury was a requirement for initial donor hepatocyte engraftment and repopulation, but too much was inhibitory to this. Long-term expansion of transplanted hepatocytes improved histological features of injury and liver function. However graft function could spontaneously decline due to transmission of senescence from host to donor cells. Modification of the host niche prior to transplantation with senotherapeutic drug ABT737 improved donor cell proliferative capacity. Targeting paracrine senescence may be a way to improve donor hepatocyte function, optimise therapy and guide translation into the clinics.

2025-01-31 | GSE240081 | GEO

Gene expression profile of HoxA9 over expressing and empty vector (EV) control Hemato-Endothelial Progenitors (HEPs) subpopulations

Project description:During hematopoietic differentiation of hESCs, HOXA9 expression parallels hematopoietic development but is restricted to the hemogenic precursors (HEP, CD31+CD34+CD45-), and diminishes as HEPs differentiate into blood cells (CD45+). Enforced expression of Hoxa9 in hESCs robustly promoted differentiation into primitive (CD34+CD45+) and total (CD45+) blood cells with higher clonogenic (CFU) potential. To identify patterns of gene expression that could explain at the molecular level the developmental impact of HOXA9 in hematopoietic commitment of hESCs, we performed gene expression profile in FACS-purified EV- and HOXA9-HEPs. 10^5 HoxA9 over expressing and EV control HEPs purified by FACS from H9 and AND1 hEBs at day 15 of hematopoietic differentiation were used for gene expression analysis using Whole Human Genome Oligo Microarray chips (Agilent Technologies).

2014-09-03 | E-GEOD-61017 | biostudies-arrayexpress

Transcriptomics of mouse hepatocyte maturation and human hepatic reprogramming

Project description:Here, we chemically induced liver progenitor cells (CLiPs) from mouse hepatocytes using a previously established protocol. To identify central protein kinases (PKs) that potentially promote the maturation of lpc-Hep cells, we profiled the transcriptomes and phosphoproteomes of freshly isolated primary mouse hepatocytes (MHs) and ALBUMIN+ hepatocytes (CLiP-Heps) cells. Based on the algorithm developed by us and experiment verification, we validated three PKs that promote mouse hepatocyte maturation. Then, we use RNA sequencing technology to identify potential regulators during hepatic reprogramming with samples from HDFs 2.25 days (FHH-2.25d) and 5 days (FHH-5d) after FOXA3, HNF1A, and HNF4A (FHH) transduction, as well as HDFs transduced with GFP for 2.25 days (GFP) as the control group. After combined analysis with phosphoproteomic data with the algorithm and experiment verification, we identified 2 PKs that may be involved in hepatic reprogramming regulation. One of the five potential regulator candidates is PIM1, which can promote the progress remarkably with overexpression. Therefore, we next perform another RNA-seq to drive the molecular mechanisms under undergoing the regulation by PIM1. Finally, we revealed that cell cycle and ferroptosis pathways are involved in the regulation via PIM1.

2022-08-06 | GSE169702 | GEO

Gene expression profiling of hepatocyte-like cells from human mesenchymal stem cells

Project description:We established a protein-based artificial transcription system and successfully engineered human hepatocyte-like cells from human umbilical cord-derived mesenchymal stem cells (MSC-UCs). We utilized four artificial transcription factors (ATFs) that targeted hepatocyte nuclear factor (HNF)1α, HNF3γ, HNF4α and GATA4 (4F), and found that treatment with 4F for 5 days converted MSC-UCs to hepatocyte-like cells (4F-Heps). We then examined gene expression profiles of 4F-Heps and compared them with those of non-treated MSC-UCs (NC) or MSC-UCs treated with NTP-EGFP protein as control protein (NE).

2022-06-09 | GSE205543 | GEO

Gene expression profile of HoxA9 over expressing and empty vector (EV) control Hemato-Endothelial Progenitors (HEPs) subpopulations

2014-09-03 | GSE61017 | GEO