scholarly journals Deep Learning Based Proarrhythmia Analysis Using Field Potentials Recorded from Human Pluripotent Stem Cells Derived Cardiomyocytes

2018 ◽  
Author(s):  
Zeinab Golgooni ◽  
Sara Mirsadeghi ◽  
Mahdieh Soleymani Baghshah ◽  
Pedram Ataee ◽  
Hossein Baharvand ◽  
...  
Keyword(s):  
Neural Network ◽  
Stem Cells ◽  
Deep Learning ◽  
Pluripotent Stem Cells ◽  
Field Potential ◽  
Input Sequence ◽  
Patient Specific ◽  
Field Potentials ◽  
Drug Induced

AbstractAimAn early characterization of drug-induced cardiotoxicity may be possible by combining comprehensive in vitro pro-arrhythmia assay and deep learning techniques. The goal of this study was to develop a deep learning method to automatically detect irregular beating rhythm as well as abnormal waveforms of field potentials in an in vitro cardiotoxicity assay using human pluripotent stem cell (hPSC) derived cardiomyocytes and multi-electrode array (MEA) system.Methods and ResultsWe included field potential waveforms from 380 experiments which obtained by application of some cardioactive drugs on healthy and/or patient-specific induced pluripotent stem cells derived cardiomyocytes (iPSC-CM). We employed convolutional and recurrent neural networks, in order to develop a new method for automatic classification of field potential recordings without using any hand-engineered features. In the proposed method, a preparation phase was initially applied to split 60-second long recordings into a series of 5-second long windows. Thereafter, the classification phase comprising of two main steps was designed. In the first step, 5-second long windows were classified using a designated convolutional neural network (CNN). In the second step, the results of 5-second long window assessments were used as the input sequence to a recurrent neural network (RNN). The output was then compared to electrophysiologist-level arrhythmia (irregularity or abnormal waveforms) detection, resulting in 0.84 accuracy, 0.84 sensitivity, 0.85 specificity, and 0.88 precision.ConclusionA novel deep learning approach based on a two-step CNN-RNN method can be used for automated analysis of “irregularity or abnormal waveforms” in an in vitro model of cardiotoxicity experiments.

scholarly journals Patient-specific hepatocyte-like cells derived from induced pluripotent stem cells model pazopanib-mediated hepatotoxicity

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Yukti Choudhury ◽  
Yi Chin Toh ◽  
Jiangwa Xing ◽  
Yinghua Qu ◽  
Jonathan Poh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Drug Testing ◽  
Kinase Inhibitor ◽  
Patient Specific ◽  
Drug Induced ◽  
Clinical Phenotypes ◽  
Induced Pluripotent

Abstract Idiosyncratic drug-induced hepatotoxicity is a major cause of liver damage and drug pipeline failure, and is difficult to study as patient-specific features are not readily incorporated in traditional hepatotoxicity testing approaches using population pooled cell sources. Here we demonstrate the use of patient-specific hepatocyte-like cells (HLCs) derived from induced pluripotent stem cells for modeling idiosyncratic hepatotoxicity to pazopanib (PZ), a tyrosine kinase inhibitor drug associated with significant hepatotoxicity of unknown mechanistic basis. In vitro cytotoxicity assays confirmed that HLCs from patients with clinically identified hepatotoxicity were more sensitive to PZ-induced toxicity than other individuals, while a prototype hepatotoxin acetaminophen was similarly toxic to all HLCs studied. Transcriptional analyses showed that PZ induces oxidative stress (OS) in HLCs in general, but in HLCs from susceptible individuals, PZ causes relative disruption of iron metabolism and higher burden of OS. Our study establishes the first patient-specific HLC-based platform for idiosyncratic hepatotoxicity testing, incorporating multiple potential causative factors and permitting the correlation of transcriptomic and cellular responses to clinical phenotypes. Establishment of patient-specific HLCs with clinical phenotypes representing population variations will be valuable for pharmaceutical drug testing.

Abstract 251: Modeling LMNA Associated Cardiomyopathy Using Patient-Specific Human Induced Pluripotent Stem Cells

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Hananeh Fonoudi ◽  
Jane Wilcox ◽  
Paul W Burridge
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Clinical Symptoms ◽  
Field Potential ◽  
Calcium Transient ◽  
Patient Specific ◽  
Control Group ◽  
Induced Pluripotent

Mutations in LMNA are the most prevalent cause of dilated cardiomyopathy (DCM), accounting for up to 5-10% all the familial DCM. LMNA encodes the lamin A/C proteins which form filamentous structures that underline nuclear envelop. Sudden cardiac death and arrhythmia are common in patients with LMNA mutations. Despite recent advancement in the field, still the exact mechanism that link the mutation in LMNA to the formation of DCM and arrythmia is still largely unknown. In this study, we have generated an in vitro model of LMNA associated DCM using patient specific human induced pluripotent stem cells (hiPSCs). A family with pathogenic deletion in LMNA gene (c. 1142-1157 + 1del17) and history of DCM were selected. hiPSCs were generated from 4 affected individuals in the family and 5 healthy individuals. hiPSCs were then directly differentiated into cardiomyocytes and assessed at day 30 post differentiation. Cardiomyocytes derived from LMNA variant patients showed significantly higher level of nuclear deformation compared to control group. Moreover, after 2 days of mechanical stress cardiomyocytes derived from LMNA variant patients showed significantly higher level of nuclear dysmorphism while the control group were not affected. Field potential analysis of cardiomyocytes derived from LMNA patients compared to controls using multielectrode array revealed significantly higher beat rate irregularity in LMNA variant group which was consistent with the clinical symptoms of the patients. Furthermore, calcium transient of the cardiomyocytes derived from LMNA variant patients were significantly different from control group. Finally, patch clamp analysis also proved our previous findings and showed electrophysiological abnormalities in patients’ cells. In summary our finding thus far shows significant electrophysiological differences between cardiomyocytes derived from LMNA variant patients and control group which could help to unravel the cellular mechanism underlying formation of arrhythmia in LMNA variant patients.

scholarly journals The Promise of Human Induced Pluripotent Stem Cells in Dental Research

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Thekkeparambil Chandrabose Srijaya ◽  
Padmaja Jayaprasad Pradeep ◽  
Rosnah Binti Zain ◽  
Sabri Musa ◽  
Noor Hayaty Abu Kasim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Patient Specific ◽  
Dental Research ◽  
Cell Based Therapy ◽  
Induced Pluripotent ◽  
Disease Specific

Induced pluripotent stem cell-based therapy for treating genetic disorders has become an interesting field of research in recent years. However, there is a paucity of information regarding the applicability of induced pluripotent stem cells in dental research. Recent advances in the use of induced pluripotent stem cells have the potential for developing disease-specific iPSC linesin vitrofrom patients. Indeed, this has provided a perfect cell source for disease modeling and a better understanding of genetic aberrations, pathogenicity, and drug screening. In this paper, we will summarize the recent progress of the disease-specific iPSC development for various human diseases and try to evaluate the possibility of application of iPS technology in dentistry, including its capacity for reprogramming some genetic orodental diseases. In addition to the easy availability and suitability of dental stem cells, the approach of generating patient-specific pluripotent stem cells will undoubtedly benefit patients suffering from orodental disorders.

scholarly journals Generation and miRNA Characterization of Equine Induced Pluripotent Stem Cells Derived from Fetal and Adult Multipotent Tissues

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Laís Vicari de Figueiredo Pessôa ◽  
Pedro Ratto Lisboa Pires ◽  
Maite del Collado ◽  
Naira Caroline Godoy Pieri ◽  
Kaiana Recchia ◽  
...  
Keyword(s):  
Stem Cells ◽  
Alkaline Phosphatase ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryoid Body ◽  
Embryoid Bodies ◽  
Mirna Profile ◽  
Patient Specific ◽  
Induced Pluripotent

Introduction. Pluripotent stem cells are believed to have greater clinical potential than mesenchymal stem cells due to their ability to differentiate into almost any cell type of an organism, and since 2006, the generation of patient-specific induced pluripotent stem cells (iPSCs) has become possible in multiple species. Objectives. We hypothesize that different cell types respond differently to the reprogramming process; thus, the goals of this study were to isolate and characterize equine adult and fetal cells and induce these cells to pluripotency for future regenerative and translational purposes. Methods. Adult equine fibroblasts (eFibros) and mesenchymal cells derived from the bone marrow (eBMmsc), adipose tissue (eADmsc), and umbilical cord tissue (eUCmsc) were isolated, their multipotency was characterized, and the cells were induced in vitro into pluripotency (eiPSCs). eiPSCs were generated through a lentiviral system using the factors OCT4, SOX2, c-MYC, and KLF4. The morphology and in vitro pluripotency maintenance potential (alkaline phosphatase detection, embryoid body formation, in vitro spontaneous differentiation, and expression of pluripotency markers) of the eiPSCs were characterized. Additionally, a miRNA profile analysis of the mesenchymal and eiPSCs was performed. Results. Multipotent cells were successfully isolated, but the eBMmsc failed to generate eiPSCs. The eADmsc-, eUCmsc-, and eFibros-derived iPSCs were positive for alkaline phosphatase, OCT4 and NANOG, were exclusively dependent on bFGF, and formed embryoid bodies. The miRNA profile revealed a segregated pattern between the eiPSCs and multipotent controls: the levels of miR-302/367 and the miR-92 family were increased in the eiPSCs, while the levels of miR-23, miR-27, and miR-30, as well as the let-7 family were increased in the nonpluripotent cells. Conclusions. We were able to generate bFGF-dependent iPSCs from eADmsc, eUCmsc, and eFibros with human OSKM, and the miRNA profile revealed that clonal lines may respond differently to the reprogramming process.

scholarly journals HDAC6 Inhibitors Rescued the Defective Axonal Mitochondrial Movement in Motor Neurons Derived from the Induced Pluripotent Stem Cells of Peripheral Neuropathy Patients with HSPB1 Mutation

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Ji-Yon Kim ◽  
So-Youn Woo ◽  
Young Bin Hong ◽  
Heesun Choi ◽  
Jisoo Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Peripheral Neuropathy ◽  
Induced Pluripotent Stem Cells ◽  
Motor Neurons ◽  
Pluripotent Stem Cells ◽  
Patient Specific ◽  
Motor Neuropathy ◽  
Mitochondrial Movement ◽  
Induced Pluripotent

The Charcot-Marie-Tooth disease 2F (CMT2F) and distal hereditary motor neuropathy 2B (dHMN2B) are caused by autosomal dominantly inherited mutations of the heat shock 27 kDa protein 1 (HSPB1) gene and there are no specific therapies available yet. Here, we assessed the potential therapeutic effect of HDAC6 inhibitors on peripheral neuropathy with HSPB1 mutation using in vitro model of motor neurons derived from induced pluripotent stem cells (iPSCs) of CMT2F and dHMN2B patients. The absolute velocity of mitochondrial movements and the percentage of moving mitochondria in axons were lower both in CMT2F-motor neurons and in dHMN2B-motor neurons than those in controls, and the severity of the defective mitochondrial movement was different between the two disease models. CMT2F-motor neurons and dHMN2B-motor neurons also showed reduced α-tubulin acetylation compared with controls. The newly developed HDAC6 inhibitors, CHEMICAL X4 and CHEMICAL X9, increased acetylation of α-tubulin and reversed axonal movement defects of mitochondria in CMT2F-motor neurons and dHMN2B-motor neurons. Our results suggest that the neurons derived from patient-specific iPSCs can be used in drug screening including HDAC6 inhibitors targeting peripheral neuropathy.

Modeling Congenital Amegakaryocytic Thrombocytopenia Using Patient-Specific Induced Pluripotent Stem Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 703-703
Author(s):  
Naoya Takayama ◽  
Shinji Hirata ◽  
Ryoko Jono-Ohnishi ◽  
Sou Nakamura ◽  
Sho-ichi Hirose ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Conflicts Of Interest ◽  
Receptor Gene ◽  
Patient Specific ◽  
Gene Correction ◽  
Donor Skin ◽  
Induced Pluripotent

Abstract Abstract 703 Patient-specific, induced pluripotent stem cells (iPSCs) enable us to study disease mechanisms and drug screening. To clarify the phenotypic alterations caused by the loss of c-MPL, the thrombopoietin (TPO) receptor, we established iPSCs derived from skin fibroblasts of a patient who received curative bone marrow transplantation for congenital amegakarycytic thrombocytopenia (CAMT) caused by the loss of the TPO receptor gene, MPL. The resultant CAMT-iPSCs exhibited mutations corresponding to the original donor skin. Then using an in vitro culture system yielding hematopoietic progenitor cells (HPCs), we evaluated the role of MPL on the early and late phases of human hematopoiesis. Although CAMT-iPSCs generated CD34+ HPCs, per se, their colony formation capability was impaired, as compared to control CD34+ HPCs. Intriguingly, both Glycophorin A (GPA)+ erythrocyte development and CD41+ megakaryocyte yields from CAMT-iPSCs were also impaired, suggesting that MPL is indispensable for MEP (megakaryocyte erythrocyte progenitors) development. Prospective analysis along with the hematopoietic hierarchy revealed that, in CAMT-iPSCs but not control iPSCs expressing MPL, mRNA expression and phosphorylation of putative signaling molecules downstream of MPL are severely impaired, as is the transition from CD34+CD43+CD41-GPA- MPP (multipotent progenitors) to CD41+GPA+ MEP. Additional analysis also indicated that c-MPL is required for maintenance of a consistent supply of megakaryocytes and erythrocytes from MEPs. Conversely, complimentary transduction of MPL into CAMT-iPSCs using a retroviral vector restored the defective erythropoiesis and megakaryopoiesis; however, excessive MPL signaling appears to promote aberrant megakaryopoiesis with CD42b (GPIba)-null platelet generation and impaired erythrocyte production. Taken together, our findings demonstrate the usefulness of CAMT-iPSCs for validation of functionality in the human hematopoiesis system. For example, it appears that MPL is not indispensable for the emergence of HPCs, but is indispensible for their maintenance, and for subsequent MEP development. Our results also strongly indicate that an appropriate expression level of an administered gene is necessary to achieve curative gene correction / therapy using patient-derived iPSCs. Disclosures: No relevant conflicts of interest to declare.

scholarly journals UM171 Regulates the Hematopoietic Differentiation of Human Acquired Aplastic Anemia-Derived Induced Pluripotent Stem Cells

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2500-2500
Author(s):  
Tellechea Maria Florencia ◽  
Flavia S. Donaires ◽  
Tiago C. Silva ◽  
Lilian F. Moreira ◽  
Yordanka Armenteros ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Patient Specific ◽  
Hematopoietic Differentiation ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Induced Pluripotent

Aplastic anemia (AA) is characterized by a hypoplastic bone marrow associated with low peripheral blood counts. In acquired cases, the immune system promotes hematopoietic stem and progenitor cell (HSPC) depletion by the action of several pro-inflammatory Th1 cytokines. The current treatment options for severe cases consist of sibling-matched allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (IST) with anti-thymocyte globulin, cyclosporine, and eltrombopag. However, most patients are not eligible for HSCT and, although about 85% of patients respond to IST with eltrombopag, a proportion of patients eventually relapse, requiring further therapies. Failure to respond adequately to immunosuppression may be attributed to the scarcity of HSPCs at the time of diagnosis. Induced pluripotent stem cells (iPSCs) are potentially an alternative source of patient-specific hematopoietic cells. Patient-specific HSPCs derived from in vitro iPSC differentiation may serve as a tool to study the disease as well as a source of hematopoietic tissue for cell therapies. The pyrimidoindole molecule UM171 induces ex vivo expansion of HSCs of human cord and peripheral blood and bone marrow, but the pathways modulated by this molecule are not well understood. Here we evaluated the hematopoietic differentiation potential of iPSCs obtained from patients with acquired AA. We further determined the effects of UM171 on this differentiation process. First, we derived iPSCs from 3 patients with acquired AA after treatment (1 female; average age, 31 years; 2 partial responders, 1 complete responder) and 3 healthy subjects (3 females; average age, 61 years) and induced differentiation in vitro through the embryoid body system in cell feeder and serum-free medium supplemented with cytokines. The hematopoietic differentiation of healthy-iPSCs yielded 19% ± 8.1% (mean ± SEM) of CD34+cells after 16 days in culture, in contrast with 11% ± 4.9% of CD34+cells obtained from the differentiation of AA-iPSCs, which corresponds to a 1.7-fold reduction in CD34+cell yield. The total number of erythroid and myeloid CFUs was lower in the AA-iPSC group as compared to healthy-iPSCs (12±4.2 vs.24±7.2; respectively; p<0.03). These findings suggest that erythroid-derived AA-iPSC have an intrinsic defect in hematopoietic differentiation. Next, we tested whether UM171 modulated hematopoietic differentiation of AA-iPSCs. We found that UM171 significantly stimulated the differentiation of both healthy and AA-iPSCs. In the healthy-iPSC group, the percentage of CD34+cells was 1.9-fold higher when treated with UM171 compared to controls treated with DMSO (37% ± 7.8% vs.19% ± 8.1%; respectively; p<0.03) and in AA-iPSCs the increase was 3.9-fold (45% ± 11% vs. 11% ± 4.9%; p<0.07). The clonogenic capacity of progenitors to produce erythroid and myeloid colonies also was augmented in both groups in comparison to DMSO (28±11 vs. 23±7.2) for healthy-iPSCs and for AA-iPSCs (23±8.5 vs. 12±4.2, p<0.06). We then investigated the molecular pathways influenced by UM171. The transcriptional profile of differentiated CD34+cells showed that UM171 up-regulated genes involved in early hematopoiesis from mesoderm (BRACHYURY and MIXL1) and primitive streak specification (APELA and APLNR), to hemangioblasts and primitive hematopoietic progenitor commitment (TDGF1, SOX17, and KLF5). We also observed the up-regulation of pro-inflammatory NF-kB activators (MAP4K1, ZAP70, and CARD11) and the anti-inflammatory gene PROCR, a marker of cultured HSCs and an NF-kB inhibitor. This balanced network has been previously suggested to be modulated by UM171 (Chagraoui et. al. Cell Stem Cell 2019). Taken together, our results showed that acquired AA-iPSCs may have intrinsic defects that impair hematopoietic differentiation in vitro. This defect may be atavic to the cell or, alternatively, the consequence of epigenetic changes in erythroid precursors provoked by the immune attack. In addition, our findings demonstrate that UM171 significantly stimulate the hematopoietic differentiation of AA-iPSCs and identified a novel molecular mechanism for UM171 as an enhancer of early hematopoietic development programs. These observations may be valuable for improving the achievement of de novo hematopoietic cells. Disclosures No relevant conflicts of interest to declare.

Pluripotent Stem Cell Modeling of Normal and Abnormal Megakaryocyte Development and Platelet Production

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1276-1276
Author(s):  
Brenden W Smith ◽  
Darrell N Kotton ◽  
Gustavo Mostoslavsky ◽  
George J. Murphy
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Peripheral Blood ◽  
Patient Specific ◽  
Directed Differentiation ◽  
Platelet Production ◽  
Blood Disorder

Abstract Abstract 1276 Thrombocytopenia is a multi-factorial blood disorder characterized by an abnormally low number of circulating platelets that can have devastating effects upon a wide swath of patients independent of age, race, or socioeconomic group. The two major reasons for thrombocytopenia are increased turnover in immune thrombocytopenia purpura (ITP) and decreased production due to bone marrow failure as a result of chemotherapy, aging, or drugs. Even in ITP, there is some evidence that decreased production may play a role in the etiology of the disease. Thus, patients not making enough platelets are usually treated with platelet transfusions, which carry risks of allergic reactions, infections, and eventually sensitization to allo-antigens making patients refractory to transfusions. With these facts in mind, there is a clear need for the development of novel, autologous sources of mature platelets, and the ability to produce patient-specific megakaryocytes from pluripotent stem cells would have a potential therapeutic role. We have developed a novel, excisable reprogramming vector (STEMCCA) capable of generating ‘clinical grade’ induced Pluripotent Stem Cells (iPSC) free of any residual reprogramming transgenes, and have employed this vector in the derivation of both normal and megakaryocyte disease-specific cell lines. To develop a novel source of platelet precursors for hematopoietic and cell-based therapy studies, we have established conditions for the efficient directed differentiation of these lines into a virtually unlimited supply of functional megakaryocyte-lineage cells that express a constellation of accepted megakaryocyte markers, appropriate Wright-Giemsa stained morphology, expected polyploidy via endoreduplication, and both normal and aberrant platelet production. iPSC-derived megakaryocytes were subsequently tagged with viral vectors expressing fluorescent proteins (for quantification of platelet contribution in peripheral blood) and/or luciferase (for in vivo imaging studies) and administered to mouse models via the retro orbital sinus. Transplanted mice were monitored for the presence of the transferred megakaryocytes and resulting platelets via Ly 5.1/5.2 chimerism as well as for the presence of GFP positive cells using FACS analysis. Peripheral blood from these mice was screened at 1 day post transplantation for chimerism and expression of GFP, and at subsequent 2 day time periods when GFP positive cells were noted in order to track the continued viability or death of the megakaryocyte-lineage cells and resulting platelets. Following these cell transfer experiments, the presence of green platelets in the peripheral blood of these mice indicated that the megakaryocyte-lineage cells produced from the directed differentiation of iPSC are indeed viable in vivo and are capable of the production of platelets. The duration of reconstitution and the functionality of the platelets derived from the iPSC generated megakaryocytes as well as those generated from embryonic stem cell (ESC) controls are currently being assessed by quantifying the labeled platelets over time, and carrying out tests of platelet function in vivo (bleeding time) and in vitro (platelet aggregation studies). Our current work focuses on the hypothesis that an iPSC-based system is capable of producing sufficient numbers of fully functional megakaryocytes to ameliorate thrombocytopenia in vivo. The implications of successfully testing this hypothesis are profound, for they suggest that early megakaryocyte and platelet development can be directly evaluated in vitro and, moreover, that megakaryocyte-lineage cells produced from patient-specific, directly differentiated iPSC lines can become a potent source for transfusion studies and regenerative medicine. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Efforts to enhance blood stem cell engraftment: Recent insights from zebrafish hematopoiesis

2017 ◽  
Vol 214 (10) ◽  
pp. 2817-2827 ◽  
Author(s):  
Julie R. Perlin ◽  
Anne L. Robertson ◽  
Leonard I. Zon
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Hematological Malignancies ◽  
Cell Types ◽  
Patient Specific ◽  
Hematopoietic Stem ◽  
Cell Engraftment ◽  
Induced Pluripotent

Hematopoietic stem cell transplantation (HSCT) is an important therapy for patients with a variety of hematological malignancies. HSCT would be greatly improved if patient-specific hematopoietic stem cells (HSCs) could be generated from induced pluripotent stem cells in vitro. There is an incomplete understanding of the genes and signals involved in HSC induction, migration, maintenance, and niche engraftment. Recent studies in zebrafish have revealed novel genes that are required for HSC induction and niche regulation of HSC homeostasis. Manipulation of these signaling pathways and cell types may improve HSC bioengineering, which could significantly advance critical, lifesaving HSCT therapies.

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