A5060825554- Hematopoietic Stem Cell Transplantation
- Single-cell and spatial transcriptomics
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Cancer Genomics and Diagnostics
- Acute Myeloid Leukemia Research
- CRISPR and Genetic Engineering
- Mesenchymal stem cell research
- Renal and related cancers
- Virus-based gene therapy research
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Pluripotent Stem Cells Research
- Gene Regulatory Network Analysis
- Neonatal Respiratory Health Research
- Erythrocyte Function and Pathophysiology
- Immunotherapy and Immune Responses
- Cancer Cells and Metastasis
- RNA Research and Splicing
- Chronic Lymphocytic Leukemia Research
- Acute Lymphoblastic Leukemia research
- Medical Imaging and Pathology Studies
- 3D Printing in Biomedical Research
- Immune responses and vaccinations
- Cell Image Analysis Techniques
Broad Center
2015-2024
University of Southern California
2015-2024
Southern California University for Professional Studies
2021-2024
Stanford University
2009-2021
Huashan Hospital
2020
Fudan University
2020
Columbia University
2017
Cincinnati Children's Hospital Medical Center
2015
Sun Yat-sen University
2012
California Institute for Regenerative Medicine
2011
Human induced pluripotent stem cells (iPSCs) provide a valuable model for regenerative medicine and human disease research. To date, however, the reprogramming efficiency of adult is still low. Recent studies have revealed that cell cycle key parameter driving epigenetic to pluripotency. As well known, retroviruses such as Moloney murine leukemia virus (MoMLV) require division integrate into host genome replicate, whereas target primary are mixture several types with different rhythms....
Significance Hematopoietic stem cells (HSCs) are the key therapeutic component of bone marrow transplantation, first and most prevalent clinical cell therapy. HSCs sustain daily life-long blood immune production through a complex stepwise lineage commitment process. In this work, we analyzed HSC at clonal level identified regulatory mechanisms that undetectable by conventional population-level studies. We uncovered distinct pathways lead to differential imbalances. Furthermore, showed...
Establishing a functional network is invaluable to our understanding of gene function, pathways, and systems-level properties an organism can be powerful resource in directing targeted experiments. In this study, we present for the laboratory mouse based on Bayesian integration diverse genetic genomic data. The resulting includes probabilistic linkages among 20,581 protein-coding genes. We show that accurately predict novel assignments components experimental evidence predictions related...
Chromatin immunoprecipitation (ChIP) is a powerful assay used to probe DNA–protein interactions. Traditional methods of implementing this are lengthy, cumbersome and require large number cells, making it difficult study rare cell types such as certain cancer stem cells. We have designed microfluidic device perform sensitive ChIP analysis on low numbers in rapid, automated fashion while preserving the specificity assay. Comparing results for two modified histone protein targets, we showed our...
Natural killer (NK) cells recognize and eliminate infected malignant cells. Their life histories are poorly understood, particularly in humans, due to lack of informative models endogenous clonal markers. Here, we apply transplantation barcoded rhesus macaque hematopoietic interrogate the landscape NK cell production, expansion, at a level long term after proliferative challenge. We identify oligoclonal populations CD56-CD16+ that characterized by marked expansions contractions over time yet...
Abstract Ageing associates with significant alterations in somatic/adult stem cells and therapies to counteract these might have profound benefits for health. In the blood, haematopoietic cell (HSC) ageing is linked several functional shortcomings. However, besides recent realization that individual HSCs be preset differentially already from young age, also age asynchronously. Evaluating prospects HSC rejuvenation therefore ultimately requires approaching those are functionally affected by...
Lentiviral vectors (LVs) are used for delivery of genes into hematopoietic stem and progenitor cells (HSPCs) in clinical trials worldwide. LVs, contrast to retroviral vectors, not associated with insertion site-associated malignant clonal expansions and, thus, considered safer. Here, however, we present a case markedly abnormal dysplastic hematopoiesis affecting the erythroid, myeloid, megakaryocytic lineages rhesus macaque transplanted HSPCs that were transduced LV containing strong murine...
Many acute and chronic diseases affect the distal lung alveoli. Alveolar epithelial cell (AEC) lines are needed to better model these diseases. We used de-identified human remnant transplant lungs develop a method establish AEC lines. The grow well in 2-dimensional (2D) culture as monolayers expressing progenitor markers. In 3-dimensional (3D) with fibroblasts, Matrigel, specific media conditions, cells form alveolar-like organoids mature markers including aquaporin 5 (AQP5),...
The geographic distribution of hematopoiesis at a clonal level is interest in understanding how hematopoietic stem and progenitor cells (HSPCs) their progeny interact with bone marrow (BM) niches during regeneration. We tagged rhesus macaque autologous HSPCs genetic barcodes, allowing tracking over time space after transplantation. found marked segregation CD34+ for least 6 mo posttransplantation, followed by very gradual mixing different BM sites subsequent months to years. Clonal mapping...
Abstract Cellular heterogeneity is a major cause of treatment resistance in cancer. Despite recent advances single-cell genomic and transcriptomic sequencing, it remains difficult to relate measured molecular profiles the cellular activities underlying Here, we present an integrated experimental system that connects single cell gene expression heterogeneous cancer growth, metastasis, response. Our integrates transcriptome profiling with DNA barcode based clonal tracking patient-derived...
Individual hematopoietic stem cells (HSCs) produce different amounts of blood upon transplantation. Taking advantage the intercellular variation, we developed an experimental and bioinformatic approach to evaluating quantitative association between gene expression cell production across individual HSCs. We found that most genes associated with exhibit only at some levels production. By mapping production, identified four distinct patterns their association. Some consistently correlate over a...
Abstract The age-associated decline in immunity manifests as imbalanced adaptive and innate immune cells, which originate from the aging of stem cells that sustain their regeneration. Aging variation across individuals is well recognized, but its mechanism remains unclear. Here, we used high-throughput single-cell technologies to compare mice same chronological age exhibited early or delayed phenotypes. We found some hematopoietic (HSCs) upregulated genes related aging, myeloid...
Hematopoietic stem cell (HSC) transplantation is the most prevalent therapy, but it remains a risky procedure. To improve this treatment, important to understand how transplanted cells rebuild blood and immune systems process impacted by variables such as HSC dose. Here, we find that, in long term following transplantation, 70%-80% of donor-HSC-derived clones do not produce all measured types. High doses lead more that exhibit balanced lymphocyte production, whereas low T-cell-specialized...
Membrane-bound factors expressed by niche stromal cells constitute a unique class of localized cues and regulate the long-term functions adult stem cells, yet little is known about underlying mechanisms. Here, we used supported lipid bilayer (SLB) to recapitulate membrane-bound interactions between hematopoietic (HSCs) cells. HSCs cluster cell factor (mSCF) at HSC-SLB interface. They further form polarized morphology with aggregated mSCF under large protrusion through synergy VCAM-1 on...