Adam D. Gracz
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View article: Tet1 safeguards lineage allocation in intestinal stem cells
Tet1 safeguards lineage allocation in intestinal stem cells Open
Intestinal stem cells (ISCs) balance self-renewal and differentiation to maintain the intestinal epithelial barrier, which is replaced weekly throughout adult life. Genetic control of ISC differentiation is well-defined relative to transcr…
View article: Quantitative 3D imaging of mouse and human intrahepatic bile ducts in homeostasis and liver injury
Quantitative 3D imaging of mouse and human intrahepatic bile ducts in homeostasis and liver injury Open
Intrahepatic bile ducts (IHBDs) form a complex hierarchical network essential for liver function. Remodeling and expansion of this network during ductular reaction (DR) is a hallmark of liver disease that can be a key indicator of disease …
View article: <i>Tritrichomonas muris</i> sensitizes the intestinal epithelium to doxorubicin-induced apoptosis
<i>Tritrichomonas muris</i> sensitizes the intestinal epithelium to doxorubicin-induced apoptosis Open
Our study found that the eukaryotic commensal Tritrichomonas muris ( Tmu) significantly increases DXR-induced intestinal apoptosis in mice. Tmu also reduces Lgr5 expression post-DXR injury and elevates inflammation and type 2 cytokine expr…
View article: Sox9 inhibits Activin A to promote biliary maturation and branching morphogenesis
Sox9 inhibits Activin A to promote biliary maturation and branching morphogenesis Open
Intrahepatic bile duct (IHBD) development produces a morphologically heterogeneous network of large "ducts" and small "ductules" by adulthood. IHBD formation is closely linked to developmental specification of biliary epithelial cells (BEC…
View article: <i>Lgr5</i> + intestinal stem cells are required for organoid survival after genotoxic injury
<i>Lgr5</i> + intestinal stem cells are required for organoid survival after genotoxic injury Open
Progenitors and mature cells can maintain the intestinal epithelium by dedifferentiation and facultative intestinal stem cell (fISC) function when active ISCs (aISCs) are lost to damage. Here, we modeled fISC activation in mouse intestinal…
View article: <i>Tritrichomonas muris</i>sensitizes the intestinal epithelium to doxorubicin-induced apoptosis
<i>Tritrichomonas muris</i>sensitizes the intestinal epithelium to doxorubicin-induced apoptosis Open
Doxorubicin (DXR) is a widely used chemotherapy drug that can induce severe intestinal mucositis. While the influence of gut bacteria on DXR-induced damage has been documented, the role of eukaryotic commensals remains unexplored. We disco…
View article: Quantitative classification of chromatin dynamics reveals regulators of intestinal stem cell differentiation
Quantitative classification of chromatin dynamics reveals regulators of intestinal stem cell differentiation Open
Intestinal stem cell (ISC) plasticity is thought to be regulated by broadly permissive chromatin shared between ISCs and their progeny. Here, we have used a Sox9EGFP reporter to examine chromatin across ISC differentiation. We find that op…
View article: <i>Lgr5</i>+ intestinal stem cells are required for organoid survival after genotoxic injury
<i>Lgr5</i>+ intestinal stem cells are required for organoid survival after genotoxic injury Open
Progenitors and mature cells can maintain the intestinal epithelium by dedifferentiation and facultative intestinal stem cell (fISC) function when active ISCs (aISCs) are lost to damage. Here, we sought to model fISC activation in intestin…
View article: <i>Sox9</i>links biliary maturation to branching morphogenesis
<i>Sox9</i>links biliary maturation to branching morphogenesis Open
SUMMARY Branching morphogenesis couples cellular differentiation with development of tissue architecture. Intrahepatic bile duct (IHBD) morphogenesis is initiated with biliary epithelial cell (BEC) specification and eventually forms a hete…
View article: Tunable fluorescent probes for detecting aldehydes in living systems
Tunable fluorescent probes for detecting aldehydes in living systems Open
Introducing 4-amino-3-thiophenol BODIPY “turn on” probe tunable to NIR wavelengths for monitoring aldehydes in tissues and living organoids by forming dihydrobenzothiazole products with aldehydes, exhibiting a remarkable fluorescence incre…
View article: SARS-CoV-2 Induces Epithelial-Enteric Neuronal Crosstalk Stimulating VIP Release
SARS-CoV-2 Induces Epithelial-Enteric Neuronal Crosstalk Stimulating VIP Release Open
Background: Diarrhea is present in up to 30–50% of patients with COVID-19. The mechanism of SARS-CoV-2-induced diarrhea remains unclear. We hypothesized that enterocyte–enteric neuron interactions were important in SARS-CoV-2-induced diarr…
View article: Sox9EGFP Defines Biliary Epithelial Heterogeneity Downstream of Yap Activity
Sox9EGFP Defines Biliary Epithelial Heterogeneity Downstream of Yap Activity Open
Our data demonstrate that Sox9EGFP levels provide readout of Yap activity and delineate BEC heterogeneity, providing a tool for assaying subpopulation-specific cellular function in the liver.
View article: CD24 and CD44 mark human intestinal epithelial cell populations with characteristics of active and facultative stem cells
CD24 and CD44 mark human intestinal epithelial cell populations with characteristics of active and facultative stem cells Open
Recent seminal studies have rapidly advanced the understanding of intestinal epithelial stem cell (IESC) biology in murine models. However, the lack of techniques suitable for isolation and subsequent downstream analysis of IESCs from huma…
View article: A high-throughput platform for stem cell niche co-cultures and downstream gene expression analysis
A high-throughput platform for stem cell niche co-cultures and downstream gene expression analysis Open
Stem cells reside in “niches”, where support cells provide signaling critical for tissue renewal. Culture methods mimic niche conditions and support the growth of stem cells in vitro. However, current functional assays preclude statistical…
View article: SOX9 Maintains Reserve Stem Cells and Preserves Radioresistance in Mouse Small Intestine
SOX9 Maintains Reserve Stem Cells and Preserves Radioresistance in Mouse Small Intestine Open
Reserve intestinal stem cells (rISCs) are quiescent/slowly cycling under homeostatic conditions, allowing for their identification with label-retention assays. rISCs mediate epithelial regeneration after tissue damage by converting to acti…
View article: Isolation and Characterization of Intestinal Stem Cells Based on Surface Marker Combinations and Colony-Formation Assay
Isolation and Characterization of Intestinal Stem Cells Based on Surface Marker Combinations and Colony-Formation Assay Open
Identification of intestinal stem cells (ISCs) has relied heavily on the use of transgenic reporters in mice, but this approach is limited by mosaic expression patterns and difficult to directly apply to human tissues. We sought to identif…
View article: Sox9<sup>EGFP</sup>defines biliary epithelial heterogeneity downstream of Yap activity
Sox9<sup>EGFP</sup>defines biliary epithelial heterogeneity downstream of Yap activity Open
Intrahepatic bile ducts are lined by biliary epithelial cells (BECs). However, defining the genetic heterogeneity of BECs remains challenging, and tools for identifying BEC subpopulations are limited. Here, we characterize Sox9 EGFP transg…
View article: Quantitative classification of chromatin dynamics reveals regulators of intestinal stem cell differentiation
Quantitative classification of chromatin dynamics reveals regulators of intestinal stem cell differentiation Open
Intestinal stem cell (ISC) plasticity is thought to be regulated by broadly permissive chromatin shared between ISCs and their progeny. Here, we have used a Sox9EGFP reporter to examine chromatin across ISC differentiation. We find that op…
View article: Optimization of 3-D organotypic primary colonic cultures for organ-on-chip applications
Optimization of 3-D organotypic primary colonic cultures for organ-on-chip applications Open
Background New advances enable long-term organotypic culture of colonic epithelial stem cells that develop into structures known as colonoids. Colonoids represent a primary tissue source acting as a potential starting material for developm…
View article: Sox9 expression marks a subset of CD24-expressing small intestine epithelial stem cells that form organoids in vitro
Sox9 expression marks a subset of CD24-expressing small intestine epithelial stem cells that form organoids in vitro Open
The inability to identify, isolate, and culture intestinal epithelial stem cells (IESCs) has been prohibitive to the study and therapeutic utilization of these cells. Using a Sox9EGFP mouse model, we demonstrate that Sox9EGFP fluorescence …
View article: A high-throughput platform for stem cell niche co-cultures and downstream gene expression analysis
A high-throughput platform for stem cell niche co-cultures and downstream gene expression analysis Open
Stem cells reside in 'niches', where support cells provide critical signalling for tissue renewal. Culture methods mimic niche conditions and support the growth of stem cells in vitro. However, current functional assays preclude statistica…
View article: The role of Sry-Box (Sox) transcription factors in epithelial stem cell biology of the gastrointestinal tract
The role of Sry-Box (Sox) transcription factors in epithelial stem cell biology of the gastrointestinal tract Open
Stem cell biology, though a well-established concept in the scientific zeitgeist, is only beginning to emerge as an independent field of study. An understanding of basic stem cell biology and its translation into clinically applicable ther…
View article: Intrinsic and extrinsic regulation of potency in the intestinal stem cell niche
Intrinsic and extrinsic regulation of potency in the intestinal stem cell niche Open
The intestinal epithelium is one of the most proliferative tissues in the adult body, undergoing near total renewal every 5-7 days. This remarkable turnover is driven by a small population of intestinal stem cells (ISCs), which maintain th…
View article: Quantitative classification of chromatin dynamics reveals regulators of intestinal stem cell differentiation
Quantitative classification of chromatin dynamics reveals regulators of intestinal stem cell differentiation Open
Intestinal stem cell (ISC) plasticity is thought to be regulated by broadly-permissive chromatin shared between ISCs and their progeny. Here, we utilize a Sox9 EGFP reporter to examine chromatin across ISC differentiation. We find that ope…