Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 54

Publication Record

Connections

Neurog3-Independent Methylation Is the Earliest Detectable Mark Distinguishing Pancreatic Progenitor Identity.
Liu J, Banerjee A, Herring CA, Attalla J, Hu R, Xu Y, Shao Q, Simmons AJ, Dadi PK, Wang S, Jacobson DA, Liu B, Hodges E, Lau KS, Gu G
(2019) Dev Cell 48: 49-63.e7
MeSH Terms: Animals, Basic Helix-Loop-Helix Transcription Factors, Cell Differentiation, Cell Lineage, Endocrine Cells, Homeodomain Proteins, Insulin-Secreting Cells, Islets of Langerhans, Mice, Nerve Tissue Proteins, Organogenesis, Pancreas, Transcription Factors
Show Abstract · Added February 6, 2019
In the developing pancreas, transient Neurog3-expressing progenitors give rise to four major islet cell types: α, β, δ, and γ; when and how the Neurog3 cells choose cell fate is unknown. Using single-cell RNA-seq, trajectory analysis, and combinatorial lineage tracing, we showed here that the Neurog3 cells co-expressing Myt1 (i.e., Myt1Neurog3) were biased toward β cell fate, while those not simultaneously expressing Myt1 (Myt1Neurog3) favored α fate. Myt1 manipulation only marginally affected α versus β cell specification, suggesting Myt1 as a marker but not determinant for islet-cell-type specification. The Myt1Neurog3 cells displayed higher Dnmt1 expression and enhancer methylation at Arx, an α-fate-promoting gene. Inhibiting Dnmts in pancreatic progenitors promoted α cell specification, while Dnmt1 overexpression or Arx enhancer hypermethylation favored β cell production. Moreover, the pancreatic progenitors contained distinct Arx enhancer methylation states without transcriptionally definable sub-populations, a phenotype independent of Neurog3 activity. These data suggest that Neurog3-independent methylation on fate-determining gene enhancers specifies distinct endocrine-cell programs.
Published by Elsevier Inc.
1 Communities
1 Members
0 Resources
13 MeSH Terms
ROCK-nmMyoII, Notch and gene-dosage link epithelial morphogenesis with cell fate in the pancreatic endocrine-progenitor niche.
Bankaitis ED, Bechard ME, Gu G, Magnuson MA, Wright CVE
(2018) Development 145:
MeSH Terms: Animals, Basic Helix-Loop-Helix Transcription Factors, Cell Differentiation, Cell Movement, Endocrine Cells, Gene Dosage, Mice, Mice, Transgenic, Nerve Tissue Proteins, Organogenesis, Pancreas, Receptors, Notch, Stem Cells, Transcriptional Activation, rho-Associated Kinases
Show Abstract · Added August 24, 2018
During mouse pancreas organogenesis, endocrine cells are born from progenitors residing in an epithelial plexus niche. After a period in a lineage-primed state, progenitors become endocrine committed via upregulation of We find that the to transition is associated with distinct stages of an epithelial egression process: narrowing the apical surface of the cell, basalward cell movement and eventual cell-rear detachment from the apical lumen surface to allow clustering as nascent islets under the basement membrane. Apical narrowing, basalward movement and transcriptional upregulation still occur without Neurog3 protein, suggesting that morphogenetic cues deployed within the plexus initiate endocrine commitment upstream or independently of Neurog3. Neurog3 is required for cell-rear detachment and complete endocrine-cell birth. The ROCK-nmMyoII pathway coordinates epithelial-cell morphogenesis and the progression through -expressing states. NmMyoII is necessary for apical narrowing, basalward cell displacement and upregulation, but all three are limited by ROCK activity. We propose that ROCK-nmMyoII activity, gene-dose and Notch signaling integrate endocrine fate allocation with epithelial plexus growth and morphogenesis, representing a feedback control circuit that coordinates morphogenesis with lineage diversification in the endocrine-birth niche.
© 2018. Published by The Company of Biologists Ltd.
2 Communities
2 Members
0 Resources
15 MeSH Terms
Cooperative function of Pdx1 and Oc1 in multipotent pancreatic progenitors impacts postnatal islet maturation and adaptability.
Kropp PA, Dunn JC, Carboneau BA, Stoffers DA, Gannon M
(2018) Am J Physiol Endocrinol Metab 314: E308-E321
MeSH Terms: Adaptation, Physiological, Animals, Animals, Newborn, Cell Differentiation, Cells, Cultured, Diet, High-Fat, Gene Expression Regulation, Developmental, Glucose, Hepatocyte Nuclear Factor 6, Homeodomain Proteins, Insulin-Secreting Cells, Islets of Langerhans, Male, Mice, Mice, Transgenic, Multipotent Stem Cells, Organogenesis, Trans-Activators
Show Abstract · Added April 15, 2019
The transcription factors pancreatic and duodenal homeobox 1 (Pdx1) and onecut1 (Oc1) are coexpressed in multipotent pancreatic progenitors (MPCs), but their expression patterns diverge in hormone-expressing cells, with Oc1 expression being extinguished in the endocrine lineage and Pdx1 being maintained at high levels in β-cells. We previously demonstrated that cooperative function of these two factors in MPCs is necessary for proper specification and differentiation of pancreatic endocrine cells. In those studies, we observed a persistent decrease in expression of the β-cell maturity factor MafA. We therefore hypothesized that Pdx1 and Oc1 cooperativity in MPCs impacts postnatal β-cell maturation and function. Here our model of Pdx1-Oc1 double heterozygosity was used to investigate the impact of haploinsufficiency for both of these factors on postnatal β-cell maturation, function, and adaptability. Examining mice at postnatal day (P) 14, we observed alterations in pancreatic insulin content in both Pdx1 heterozygotes and double heterozygotes. Gene expression analysis at this age revealed significantly decreased expression of many genes important for glucose-stimulated insulin secretion (e.g., Glut2, Pcsk1/2, Abcc8) exclusively in double heterozygotes. Analysis of P14 islets revealed an increase in the number of mixed islets in double heterozygotes. We predicted that double-heterozygous β-cells would have an impaired ability to respond to stress. Indeed, we observed that β-cell proliferation fails to increase in double heterozygotes in response to either high-fat diet or placental lactogen. We thus report here the importance of cooperation between regulatory factors early in development for postnatal islet maturation and adaptability.
0 Communities
1 Members
0 Resources
MeSH Terms
Differential Expression of NF2 in Neuroepithelial Compartments Is Necessary for Mammalian Eye Development.
Moon KH, Kim HT, Lee D, Rao MB, Levine EM, Lim DS, Kim JW
(2018) Dev Cell 44: 13-28.e3
MeSH Terms: Adaptor Proteins, Signal Transducing, Animals, Cell Lineage, Cell Polarity, Cells, Cultured, Cilia, Gene Expression Regulation, Developmental, Humans, Hyperplasia, Mice, Mice, Knockout, Neural Stem Cells, Neurofibromin 2, Organogenesis, Phenotype, Phosphoproteins, Protein-Serine-Threonine Kinases, Retinal Pigment Epithelium, Transcription Factors
Show Abstract · Added February 14, 2018
The optic neuroepithelial continuum of vertebrate eye develops into three differentially growing compartments: the retina, the ciliary margin (CM), and the retinal pigment epithelium (RPE). Neurofibromin 2 (Nf2) is strongly expressed in slowly expanding RPE and CM compartments, and the loss of mouse Nf2 causes hyperplasia in these compartments, replicating the ocular abnormalities seen in human NF2 patients. The hyperplastic ocular phenotypes were largely suppressed by heterozygous deletion of Yap and Taz, key targets of the Nf2-Hippo signaling pathway. We also found that, in addition to feedback transcriptional regulation of Nf2 by Yap/Taz in the CM, activation of Nf2 expression by Mitf in the RPE and suppression by Sox2 in retinal progenitor cells are necessary for the differential growth of the corresponding cell populations. Together, our findings reveal that Nf2 is a key player that orchestrates the differential growth of optic neuroepithelial compartments during vertebrate eye development.
Copyright © 2017 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
19 MeSH Terms
EGFR signalling controls cellular fate and pancreatic organogenesis by regulating apicobasal polarity.
Löf-Öhlin ZM, Nyeng P, Bechard ME, Hess K, Bankaitis E, Greiner TU, Ameri J, Wright CV, Semb H
(2017) Nat Cell Biol 19: 1313-1325
MeSH Terms: Animals, Basic Helix-Loop-Helix Transcription Factors, Cell Differentiation, Cell Polarity, Epithelial Cells, ErbB Receptors, Insulin-Secreting Cells, Mice, Mice, Knockout, Morphogenesis, Nerve Tissue Proteins, Neuropeptides, Organogenesis, Phosphatidylinositol 3-Kinases, Protein Kinase C, Signal Transduction, rac1 GTP-Binding Protein
Show Abstract · Added November 7, 2017
Apicobasal polarity is known to affect epithelial morphogenesis and cell differentiation, but it remains unknown how these processes are mechanistically orchestrated. We find that ligand-specific EGFR signalling via PI(3)K and Rac1 autonomously modulates apicobasal polarity to enforce the sequential control of morphogenesis and cell differentiation. Initially, EGF controls pancreatic tubulogenesis by negatively regulating apical polarity induction. Subsequently, betacellulin, working via inhibition of atypical protein kinase C (aPKC), causes apical domain constriction within neurogenin3 endocrine progenitors, which results in reduced Notch signalling, increased neurogenin3 expression, and β-cell differentiation. Notably, the ligand-specific EGFR output is not driven at the ligand level, but seems to have evolved in response to stage-specific epithelial influences. The EGFR-mediated control of β-cell differentiation via apical polarity is also conserved in human neurogenin3 cells. We provide insight into how ligand-specific EGFR signalling coordinates epithelial morphogenesis and cell differentiation via apical polarity dynamics.
2 Communities
1 Members
0 Resources
17 MeSH Terms
Lkb1 regulates granule cell migration and cortical folding of the cerebellar cortex.
Ryan KE, Kim PS, Fleming JT, Brignola E, Cheng FY, Litingtung Y, Chiang C
(2017) Dev Biol 432: 165-177
MeSH Terms: Animals, Cell Differentiation, Cell Division, Cell Movement, Cerebellar Cortex, Cytoplasmic Granules, Hedgehog Proteins, Mice, Nerve Tissue Proteins, Neurons, Organogenesis, Protein-Serine-Threonine Kinases, Signal Transduction
Show Abstract · Added April 10, 2019
Cerebellar growth and foliation require the Hedgehog-driven proliferation of granule cell precursors (GCPs) in the external granule layer (EGL). However, that increased or extended GCP proliferation generally does not elicit ectopic folds suggests that additional determinants control cortical expansion and foliation during cerebellar development. Here, we find that genetic loss of the serine-threonine kinase Liver Kinase B1 (Lkb1) in GCPs increased cerebellar cortical size and foliation independent of changes in proliferation or Hedgehog signaling. This finding is unexpected given that Lkb1 has previously shown to be critical for Hedgehog pathway activation in cultured cells. Consistent with unchanged proliferation rate of GCPs, the cortical expansion of Lkb1 mutants is accompanied by thinning of the EGL. The plane of cell division, which has been implicated in diverse processes from epithelial surface expansions to gyrification of the human cortex, remains unchanged in the mutants when compared to wild-type controls. However, we find that Lkb1 mutants display delayed radial migration of post-mitotic GCPs that coincides with increased cortical size, suggesting that aberrant cell migration may contribute to the cortical expansion and increase foliation. Taken together, our results reveal an important role for Lkb1 in regulating cerebellar cortical size and foliation in a Hedgehog-independent manner.
Copyright © 2017 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
MeSH Terms
Stochastic priming and spatial cues orchestrate heterogeneous clonal contribution to mouse pancreas organogenesis.
Larsen HL, Martín-Coll L, Nielsen AV, Wright CVE, Trusina A, Kim YH, Grapin-Botton A
(2017) Nat Commun 8: 605
MeSH Terms: Acinar Cells, Animals, Cell Differentiation, Cell Lineage, Cell Proliferation, Computer Simulation, Gene Expression Profiling, Mice, Organogenesis, Pancreas, Single-Cell Analysis
Show Abstract · Added October 3, 2017
Spatiotemporal balancing of cellular proliferation and differentiation is crucial for postnatal tissue homoeostasis and organogenesis. During embryonic development, pancreatic progenitors simultaneously proliferate and differentiate into the endocrine, ductal and acinar lineages. Using in vivo clonal analysis in the founder population of the pancreas here we reveal highly heterogeneous contribution of single progenitors to organ formation. While some progenitors are bona fide multipotent and contribute progeny to all major pancreatic cell lineages, we also identify numerous unipotent endocrine and ducto-endocrine bipotent clones. Single-cell transcriptional profiling at E9.5 reveals that endocrine-committed cells are molecularly distinct, whereas multipotent and bipotent progenitors do not exhibit different expression profiles. Clone size and composition support a probabilistic model of cell fate allocation and in silico simulations predict a transient wave of acinar differentiation around E11.5, while endocrine differentiation is proportionally decreased. Increased proliferative capacity of outer progenitors is further proposed to impact clonal expansion.
2 Communities
0 Members
0 Resources
11 MeSH Terms
Pathways to clinical CLARITY: volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease.
Hsueh B, Burns VM, Pauerstein P, Holzem K, Ye L, Engberg K, Wang AC, Gu X, Chakravarthy H, Arda HE, Charville G, Vogel H, Efimov IR, Kim S, Deisseroth K
(2017) Sci Rep 7: 5899
MeSH Terms: Animals, Disease, Female, Humans, Hydrogels, Imaging, Three-Dimensional, Mice, Inbred C57BL, Neural Crest, Neurosecretory Systems, Organogenesis, Pancreas
Show Abstract · Added October 31, 2017
Three-dimensional tissue-structural relationships are not well captured by typical thin-section histology, posing challenges for the study of tissue physiology and pathology. Moreover, while recent progress has been made with intact methods for clearing, labeling, and imaging whole organs such as the mature brain, these approaches are generally unsuitable for soft, irregular, and heterogeneous tissues that account for the vast majority of clinical samples and biopsies. Here we develop a biphasic hydrogel methodology, which along with automated analysis, provides for high-throughput quantitative volumetric interrogation of spatially-irregular and friable tissue structures. We validate and apply this approach in the examination of a variety of developing and diseased tissues, with specific focus on the dynamics of normal and pathological pancreatic innervation and development, including in clinical samples. Quantitative advantages of the intact-tissue approach were demonstrated compared to conventional thin-section histology, pointing to broad applications in both research and clinical settings.
1 Communities
0 Members
0 Resources
11 MeSH Terms
Coordinated Proliferation and Differentiation of Human-Induced Pluripotent Stem Cell-Derived Cardiac Progenitor Cells Depend on Bone Morphogenetic Protein Signaling Regulation by GREMLIN 2.
Bylund JB, Trinh LT, Awgulewitsch CP, Paik DT, Jetter C, Jha R, Zhang J, Nolan K, Xu C, Thompson TB, Kamp TJ, Hatzopoulos AK
(2017) Stem Cells Dev 26: 678-693
MeSH Terms: Bone Morphogenetic Proteins, Cell Differentiation, Cell Line, Cell Proliferation, Cells, Cultured, Gene Expression Profiling, Gene Expression Regulation, Developmental, Humans, Induced Pluripotent Stem Cells, Intercellular Signaling Peptides and Proteins, Myocardium, Myocytes, Cardiac, Organogenesis, Signal Transduction, Stem Cells
Show Abstract · Added September 6, 2017
Heart development depends on coordinated proliferation and differentiation of cardiac progenitor cells (CPCs), but how the two processes are synchronized is not well understood. Here, we show that the secreted Bone Morphogenetic Protein (BMP) antagonist GREMLIN 2 (GREM2) is induced in CPCs shortly after cardiac mesoderm specification during differentiation of human pluripotent stem cells. GREM2 expression follows cardiac lineage differentiation independently of the differentiation method used, or the origin of the pluripotent stem cells, suggesting that GREM2 is linked to cardiogenesis. Addition of GREM2 protein strongly increases cardiomyocyte output compared to established procardiogenic differentiation methods. Our data show that inhibition of canonical BMP signaling by GREM2 is necessary to promote proliferation of CPCs. However, canonical BMP signaling inhibition alone is not sufficient to induce cardiac differentiation, which depends on subsequent JNK pathway activation specifically by GREM2. These findings may have broader implications in the design of approaches to orchestrate growth and differentiation of pluripotent stem cell-derived lineages that depend on precise regulation of BMP signaling.
0 Communities
1 Members
0 Resources
15 MeSH Terms
The mammal-specific Pdx1 Area II enhancer has multiple essential functions in early endocrine cell specification and postnatal β-cell maturation.
Yang YP, Magnuson MA, Stein R, Wright CV
(2017) Development 144: 248-257
MeSH Terms: Animals, Binding Sites, Cell Differentiation, Embryo, Mammalian, Enhancer Elements, Genetic, Gene Expression Regulation, Developmental, Homeodomain Proteins, Insulin-Secreting Cells, Islets of Langerhans, Mammals, Mice, Mice, Transgenic, Organogenesis, Species Specificity, Trans-Activators
Show Abstract · Added December 29, 2016
The transcription factor Pdx1 is required for multiple aspects of pancreatic organogenesis. It remains unclear to what extent Pdx1 expression and function depend upon trans-activation through 5' conserved cis-regulatory regions and, in particular, whether the mammal-specific Area II (-2139 to -1958 bp) affects minor or major aspects of organogenesis. We show that Area II is a primary effector of endocrine-selective transcription in epithelial multipotent cells, nascent endocrine progenitors, and differentiating and mature β cells in vivo Pdx1 mice exhibit a massive reduction in endocrine progenitor cells and progeny hormone-producing cells, indicating that Area II activity is fundamental to mounting an effective endocrine lineage-specification program within the multipotent cell population. Creating an Area II-deleted state within already specified Neurog3-expressing endocrine progenitor cells increased the proportion of glucagon α relative to insulin β cells, associated with the transcriptional and epigenetic derepression of the α-cell-determining Arx gene in endocrine progenitors. There were also glucagon and insulin co-expressing cells, and β cells that were incapable of maturation. Creating the Pdx1 state after cells entered an insulin-expressing stage led to immature and dysfunctional islet β cells carrying abnormal chromatin marking in vital β-cell-associated genes. Therefore, trans-regulatory integration through Area II mediates a surprisingly extensive range of progenitor and β-cell-specific Pdx1 functions.
© 2017. Published by The Company of Biologists Ltd.
2 Communities
3 Members
0 Resources
15 MeSH Terms