A5090265299- Neonatal Respiratory Health Research
- Congenital Diaphragmatic Hernia Studies
- Renal and related cancers
- Tracheal and airway disorders
- Congenital gastrointestinal and neural anomalies
- Tissue Engineering and Regenerative Medicine
- Congenital heart defects research
- Ethics and Legal Issues in Pediatric Healthcare
- Cancer Cells and Metastasis
- Digestive system and related health
- Gastrointestinal motility and disorders
University of Michigan
2020-2025
Human intestinal organoids (HIOs) derived from human pluripotent stem cells co-differentiate both epithelial and mesenchymal lineages in vitro but lack important cell types such as neurons, endothelial cells, smooth muscle, which limits translational potential. Here, we demonstrate that the niche factor, EPIREGULIN (EREG), enhances HIO differentiation with epithelium, mesenchyme, enteric neuroglial populations, organized muscle a single differentiation, without need for co-culture. When...
Bud tip progenitors (BTPs) in the developing lung give rise to all epithelial cell types found airways and alveoli. This work aimed develop an iPSC organoid model enriched with NKX2-1+ BTP-like cells. Building on previous studies, we optimized a directed differentiation paradigm generate spheroids more robust NKX2-1 expression. Spheroids were expanded into organoids that possessed NKX2-1+/CPM+ cells, which increased number over time. Single RNA-sequencing analysis revealed high degree of...
The human respiratory epithelium is derived from a progenitor cell in the distal buds of developing lung. These "bud tip progenitors" are regulated by reciprocal signaling with surrounding mesenchyme; however, mesenchymal heterogeneity and function lung poorly understood. We interrogated single-cell RNA sequencing data multiple specimens identified population present during development that highly enriched for expression WNT agonist RSPO2, we found adjacent bud progenitors RSPO2 receptor...
Using scRNA-seq and microscopy, we describe a cell that is enriched in the lower airways of developing human lung identified by unique coexpression SCGB3A2/SFTPB/CFTR . To functionally interrogate these cells, apply single-cell barcode-based lineage tracing method, called CellTagging, to track fate cells during airway organoid differentiation vitro. Lineage reveals have distinct potential from basal giving rise predominantly pulmonary neuroendocrine subset multiciliated distinguished high C6...
Abstract Human intestinal organoids (HIOs) derived from human pluripotent stem cells co-differentiate both epithelial and mesenchymal lineages in vitro but lack important cell types such as neurons, endothelial cells, smooth muscle. Here, we report an method to derive HIOs with epithelium, mesenchyme, enteric neuroglial populations, organized muscle a single differentiation, without the need for co-culture. When transplanted into murine host, these populations expand organize support...
Alveolar type 2 (AT2) cells function as stem in the adult lung and aid repair after injury. The current study aimed to understand signaling events that control differentiation of this therapeutically relevant cell during human development. Using explant organoid models, we identified opposing effects TGFβ- BMP-signaling, where inhibition activation BMP-signaling context high WNT- FGF-signaling efficiently differentiated early progenitors into AT2-like vitro. manner exhibit surfactant...
SUMMARY Mammalian respiratory system development is regulated by complex reciprocal signaling events that take place between epithelial cells and the surrounding mesenchymal cells; however, heterogeneity function in developing human lung poorly understood. We interrogated single cell RNA sequencing data from multiple specimens identified a population present during highly enriched for expression of WNT agonist R-SPONDIN2 ( RSPO2 ), we found adjacent bud tip progenitors are receptor LGR5 . By...
Organs are composed of diverse cell types that change across space and time during development. To interrogate this diversity, we micro-dissected developing human lungs along the proximal-distal axis late pseudoglandular stage generated an integrated analysis single-nucleus sequencing spatial transcriptomics, creating a cellularly-resolved atlas lung. These rich datasets revealed positional niches cellular heterogeneity axis, including identification unique population TP63+ basal cells,...
Alveolar type 2 (AT2) cells function as stem in the adult lung and aid repair after injury. The current study aimed to understand signaling events that control differentiation of this therapeutically relevant cell during human development. Using explant organoid models, we identified opposing effects TGFβ- BMP-signaling, where inhibition activation BMP-signaling context high WNT- FGF-signaling efficiently differentiated early progenitors into AT2-like vitro . manner exhibit surfactant...
ABSTRACT Bud tip progenitors (BTPs) in the developing lung give rise to all epithelial cell types found airways and alveoli. The current work aimed develop an iPSC organoid model enriched with stable NKX2-1 + BTP-like cells. Building on prior work, we optimized a directed differentiation paradigm generate spheroids robust expression. Spheroids were expanded into organoids that possessed /CPM cells, which increased number over time. Single RNA-sequencing analysis revealed high degree of...
ABSTRACT Recent advances using single cell genomic approaches have identified new epithelial types and uncovered cellular heterogeneity in the murine human lung (1). Here, scRNA-seq microscopy we identify describe a secretory-like that is enriched small airways of developing by unique co-expression SCGB3A2/SFTPB/CFTR . To place these cells hierarchy airway development, apply barcode-based lineage tracing method track fate during organoid differentiation vitro (2). Lineage revealed distinct...