scholarly journals Pre-Border Gene Foxb1 Regulates the Differentiation Timing and Autonomic Neuronal Potential of Human Neural Crest Cells

2019 ◽  
Author(s):  
Alan W. Leung ◽  
Francesc López-Giráldez ◽  
Cayla Broton ◽  
Kaixuan Lin ◽  
Maneeshi S. Prasad ◽  
...  
Keyword(s):  
Neural Crest ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Stem Cell Differentiation ◽  
Human Pluripotent Stem Cell ◽  
Cell Fate Decisions ◽  
Pluripotency Factors ◽  
Forkhead Box ◽  
Insight Into

SUMMARYWhat 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.

scholarly journals GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency

2017 ◽  
Vol 114 (45) ◽  
pp. E9579-E9588 ◽  
Author(s):  
Christian Krendl ◽  
Dmitry Shaposhnikov ◽  
Valentyna Rishko ◽  
Chaido Ori ◽  
Christoph Ziegenhain ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Molecular Basis ◽  
Pluripotent Stem Cell ◽  
Stem Cell Differentiation ◽  
Surface Marker ◽  
Specific Gene ◽  
Human Pluripotent Stem Cell ◽  
Human Embryogenesis

To elucidate the molecular basis of BMP4-induced differentiation of human pluripotent stem cells (PSCs) toward progeny with trophectoderm characteristics, we produced transcriptome, epigenome H3K4me3, H3K27me3, and CpG methylation maps of trophoblast progenitors, purified using the surface marker APA. We combined them with the temporally resolved transcriptome of the preprogenitor phase and of single APA+ cells. This revealed a circuit of bivalent TFAP2A, TFAP2C, GATA2, and GATA3 transcription factors, coined collectively the “trophectoderm four” (TEtra), which are also present in human trophectoderm in vivo. At the onset of differentiation, the TEtra factors occupy multiple sites in epigenetically inactive placental genes and in OCT4. Functional manipulation of GATA3 and TFAP2A indicated that they directly couple trophoblast-specific gene induction with suppression of pluripotency. In accordance, knocking down GATA3 in primate embryos resulted in a failure to form trophectoderm. The discovery of the TEtra circuit indicates how trophectoderm commitment is regulated in human embryogenesis.

scholarly journals Shaping axial identity during human pluripotent stem cell differentiation to neural crest cells

2022 ◽  
Author(s):  
Fay Cooper ◽  
Anestis Tsakiridis
Keyword(s):  
Neural Crest ◽  
Pluripotent Stem Cells ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Developmental Origins ◽  
Human Pluripotent Stem Cell ◽  
Recent Advances ◽  
Distinct Cell

The neural crest (NC) is a multipotent cell population which can give rise to a vast array of derivatives including neurons and glia of the peripheral nervous system, cartilage, cardiac smooth muscle, melanocytes and sympathoadrenal cells. An attractive strategy to model human NC development and associated birth defects as well as produce clinically relevant cell populations for regenerative medicine applications involves the in vitro generation of NC from human pluripotent stem cells (hPSCs). However, in vivo, the potential of NC cells to generate distinct cell types is determined by their position along the anteroposterior (A–P) axis and, therefore the axial identity of hPSC-derived NC cells is an important aspect to consider. Recent advances in understanding the developmental origins of NC and the signalling pathways involved in its specification have aided the in vitro generation of human NC cells which are representative of various A–P positions. Here, we explore recent advances in methodologies of in vitro NC specification and axis patterning using hPSCs.

scholarly journals MYC Controls Human Pluripotent Stem Cell Fate Decisions through Regulation of Metabolic Flux

2017 ◽  
Vol 21 (4) ◽  
pp. 502-516.e9 ◽  
Author(s):  
Timothy S. Cliff ◽  
Tianming Wu ◽  
Benjamin R. Boward ◽  
Amelia Yin ◽  
Hang Yin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Pluripotent Stem Cell ◽  
Metabolic Flux ◽  
Human Pluripotent Stem Cell ◽  
Stem Cell Fate ◽  
Cell Fate Decisions

scholarly journals Polyamine-controlled proliferation and protein biosynthesis are independent determinants of hair follicle stem cell fate

2020 ◽  
Author(s):  
Kira Allmeroth ◽  
Christine S. Kim ◽  
Andrea Annibal ◽  
Andromachi Pouikli ◽  
Carlos Andrés Chacón-Martínez ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hair Follicle ◽  
Cell Fate ◽  
Protein Biosynthesis ◽  
Mrna Translation ◽  
Stem Cell Differentiation ◽  
List Type ◽  
Stem Cell Fate ◽  
Cell Fate Decisions ◽  
Hair Follicle Stem Cell

AbstractStem cell differentiation is accompanied by an increase in mRNA translation. The rate of protein biosynthesis is influenced by the polyamines putrescine, spermidine, and spermine that are essential for cell growth and stem cell maintenance. However, the role of polyamines as endogenous effectors of stem cell fate and whether they act through translational control remains obscure. Here, we investigated the function of polyamines in stem cell fate decisions using hair follicle stem cell (HFSC) organoids. HFSCs showed lower translation rates than progenitor cells, and a forced suppression of translation by direct targeting of the ribosome or through specific depletion of natural polyamines elevated stemness. In addition, we identified N1-acetylspermidine as a novel parallel regulator of cell fate decisions, increasing proliferation without reducing translation. Overall, this study delineates the diverse routes of polyamine metabolism-mediated regulation of stem cell fate decisions.Key PointsLow mRNA translation rates characterize hair follicle stem cell (HFSC) stateDepletion of natural polyamines enriches HFSCs via reduced translationN1-acetylspermidine promotes HFSC state without reducing translationN1-acetylspermidine expands the stem cell pool through elevated proliferation

Conservation of the Notch signalling pathway in mammalian neurogenesis

Development ◽  
1997 ◽  
Vol 124 (6) ◽  
pp. 1139-1148 ◽  
Author(s):  
J.L. Pompa de la ◽  
A. Wakeham ◽  
K.M. Correia ◽  
E. Samper ◽  
S. Brown ◽  
...  
Keyword(s):  
Cell Fate ◽  
Notch Pathway ◽  
Stem Cell Differentiation ◽  
Notch Signalling ◽  
Signalling Pathway ◽  
Notch Signalling Pathway ◽  
Altered Expression ◽  
Cell Fate Decisions ◽  
Targeted Mutation ◽  
Multiple Cell

The Notch pathway functions in multiple cell fate determination processes in invertebrate embryos, including the decision between the neuroblast and epidermoblast lineages in Drosophila. In the mouse, targeted mutation of the Notch pathway genes Notch1 and RBP-Jk has demonstrated a role for these genes in somite segmentation, but a function in neurogenesis and in cell fate decisions has not been shown. Here we show that these mutations lead to altered expression of the Notch signalling pathway homologues Hes-5, Mash-1 and Dll1, resulting in enhanced neurogenesis. Precocious neuronal differentiation is indicated by the expanded expression domains of Math4A, neuroD and NSCL-1. The RBP-Jk mutation has stronger effects on expression of these genes than does the Notch1 mutation, consistent with functional redundancy of Notch genes in neurogenesis. Our results demonstrate conservation of the Notch pathway and its regulatory mechanisms from fly to mouse, and support a role for the murine Notch signalling pathway in the regulation of neural stem cell differentiation.

Differentiating human pluripotent stem cells into vascular smooth muscle cells in three dimensional thermoreversible hydrogels

2019 ◽  
Vol 7 (1) ◽  
pp. 347-361 ◽  
Author(s):  
Haishuang Lin ◽  
Qian Du ◽  
Qiang Li ◽  
Ou Wang ◽  
Zhanqi Wang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Three Dimensional ◽  
Muscle Cells ◽  
Human Pluripotent Stem Cell ◽  
Scalable Production

3D thermoreversible PNIPAAm-PEG hydrogels are used for scalable production of human pluripotent stem cell-derived vascular smooth muscle cells.

scholarly journals Modeling endodermal organ development and diseases using human pluripotent stem cell-derived organoids

2020 ◽  
Vol 12 (8) ◽  
pp. 580-592
Author(s):  
Fong Cheng Pan ◽  
Todd Evans ◽  
Shuibing Chen
Keyword(s):  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Disease Modeling ◽  
State Of The Art ◽  
Directed Differentiation ◽  
Organ Development ◽  
Human Pluripotent Stem Cell ◽  
Human Organ ◽  
Current State

Abstract Recent advances in development of protocols for directed differentiation from human pluripotent stem cells (hPSCs) to defined lineages, in combination with 3D organoid technology, have facilitated the generation of various endoderm-derived organoids for in vitro modeling of human gastrointestinal development and associated diseases. In this review, we discuss current state-of-the-art strategies for generating hPSC-derived endodermal organoids including stomach, liver, pancreatic, small intestine, and colonic organoids. We also review the advantages of using this system to model various human diseases and evaluate the shortcomings of this technology. Finally, we emphasize how other technologies, such as genome editing and bioengineering, can be incorporated into the 3D hPSC-organoid models to generate even more robust and powerful platforms for understanding human organ development and disease modeling.

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