Maneeshi S. Prasad
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Research Interests
Maneeshi S. Prasad has a total of 14 co-authors. Here are the top co-authors by number of shared publications:
- Alan W. Leung
Yale University
2 shared publications - Martin I. Garcia-Castro
Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA
2 shared publications - Andrew Xiao
Department of Genetics, Yale University School of Medicine, New Haven, USA
1 shared publication - Cayla Broton
Yale University
1 shared publication - Francesc Lopez-Giraldez
Yale Center for Genome Analysis, Yale University
1 shared publication - Gustavo A. Gomez
University of California, Riverside
1 shared publication
Latest Publications
- Open Access
Pre-Border Gene Foxb1 Regulates the Differentiation Timing and Autonomic Neuronal Potential of Human Neural Crest Cells
SUMMARY: What are the factors that are induced during the transitory phases from pluripotent stem cells to lineage specified cells, how are they regulated, and what are their functional contributions are fundamental questions for basic developmental biology and clinical research. Here, we uncover a set of pre-border (pB) gene candidates, including forkhead box B1 (FOXB1), induced during human neural crest (NC) cell development. We characterize their associated enhancers that are bound by pluripotency factors and rapidly activated by β-catenin-mediated signaling during differentiation. Surprisingly, the endogenous transient expression of FOXB1 directly regulates multiple early NC and neural progenitor loci including PAX7 , MSX2 , SOX1 , and ASCL1 , controls the timing of NC fate acquisition, and differentially activates autonomic neurogenic versus mesenchymal fates in mature NC cells. Our findings provide further insight into the concept of the less characterized pB state and clearly establishes FOXB1 as a key regulator in early cell fate decisions during human pluripotent stem cell differentiation.
Open AccessPre-Border Gene Foxb1 Regulates the Differentiation Timing and Autonomic Neuronal Potential of Human Neural Crest Cells
SUMMARY: What are the factors that are induced during the transitory phases from pluripotent stem cells to lineage specified cells, how are they regulated, and what are their functional contributions are fundamental questions for basic developmental biology and clinical research. Here, we uncover a set of pre-border (pB) gene candidates, including forkhead box B1 (FOXB1), induced during human neural crest (NC) cell development. We characterize their associated enhancers that are bound by pluripotency factors and rapidly activated by β-catenin-mediated signaling during differentiation. Surprisingly, the endogenous transient expression of FOXB1 directly regulates multiple early NC and neural progenitor loci including PAX7 , MSX2 , SOX1 , and ASCL1 , controls the timing of NC fate acquisition, and differentially activates autonomic neurogenic versus mesenchymal fates in mature NC cells. Our findings provide further insight into the concept of the less characterized pB state and clearly establishes FOXB1 as a key regulator in early cell fate decisions during human pluripotent stem cell differentiation.
- Open Access
WNT/β-CATENIN modulates the axial identity of ES derived human neural crest
The WNT/β-CATENIN pathway is critical for neural crest (NC) formation. However, the effects of the magnitude of the signal remains poorly defined. Here we evaluate the consequences of WNT magnitude variation in a robust model of human NC formation. This model is based on human embryonic stem cells induced by WNT signaling through the small molecule CHIR9902. In addition to its known effect on NC formation, we find that the WNT signal modulates the anterior-posterior axial identity of NCCs in a dose dependent manner, with low WNT leading to anterior OTX+, HOX-NC, and high WNT leading to posterior OTX−, HOX+ NC. Differentiation tests of posterior NC confirm expected derivatives including posterior specific adrenal derivatives, and display partial capacity to generate anterior ectomesenchymal derivatives. Furthermore, unlike anterior NC, posterior NC transit through a TBXT+/SOX2+ neuromesodermal precursor-like intermediate. Finally, we analyze the contributions of other signaling pathways in posterior NC formation, and suggest a critical role for FGF in survival/proliferation, and a requirement of BMP for NC maturation. As expected RA and FGF are able to modulate HOX expression in the posterior NC, but surprisingly, RA supplementation prohibits anterior, but only reduces, posterior NC formation. This work reveals for the first time that the amplitude of WNT signaling can modulate the axial identity of NC cells in humans.
Open AccessWNT/β-CATENIN modulates the axial identity of ES derived human neural crest
The WNT/β-CATENIN pathway is critical for neural crest (NC) formation. However, the effects of the magnitude of the signal remains poorly defined. Here we evaluate the consequences of WNT magnitude variation in a robust model of human NC formation. This model is based on human embryonic stem cells induced by WNT signaling through the small molecule CHIR9902. In addition to its known effect on NC formation, we find that the WNT signal modulates the anterior-posterior axial identity of NCCs in a dose dependent manner, with low WNT leading to anterior OTX+, HOX-NC, and high WNT leading to posterior OTX−, HOX+ NC. Differentiation tests of posterior NC confirm expected derivatives including posterior specific adrenal derivatives, and display partial capacity to generate anterior ectomesenchymal derivatives. Furthermore, unlike anterior NC, posterior NC transit through a TBXT+/SOX2+ neuromesodermal precursor-like intermediate. Finally, we analyze the contributions of other signaling pathways in posterior NC formation, and suggest a critical role for FGF in survival/proliferation, and a requirement of BMP for NC maturation. As expected RA and FGF are able to modulate HOX expression in the posterior NC, but surprisingly, RA supplementation prohibits anterior, but only reduces, posterior NC formation. This work reveals for the first time that the amplitude of WNT signaling can modulate the axial identity of NC cells in humans.