scholarly journals Pluripotent stem cells for the study of early human embryology

2021 ◽  
Vol 63 (2) ◽  
pp. 104-115
Author(s):  
Katsunori Semi ◽  
Yasuhiro Takashima
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Embryology ◽  
Early Human

scholarly journals Protocol for controlled modeling of human epiblast and amnion development using stem cells

2019 ◽  
Author(s):  
Yi Zheng ◽  
Jianping Fu
Keyword(s):  
Stem Cells ◽  
Primordial Germ Cells ◽  
Primitive Streak ◽  
Human Embryos ◽  
Vitro Fertilization ◽  
Human Embryology ◽  
Post Implantation ◽  
Advance Knowledge ◽  
Early Human

Abstract Due to the inaccessibility of post-implantation human embryos and the restriction on in-vitro fertilization (IVF) embryos cultured beyond 14 days, the knowledge of early post-implantation human embryogenesis remains extremely limited. Recently, we have developed a microfluidic in-vitro platform, based on human pluripotent stem cells (hPSCs), which is capable of recapitulating several key developmental landmarks of early human post-implantation embryonic development, including lumenogenesis of the epiblast (EPI), amniogenesis, and specification of primordial germ cells (PGCs) and of primitive streak (PS) cells. Given its controllability and reproducibility, the microfluidic platform provides a powerful experimental platform to advance knowledge of human embryology and reproduction. This protocol describes the preparation of the microfluidic device and its implementation for modeling human post-implantation epiblast and amnion development using hPSCs.

scholarly journals Genome-wide Studies Reveal the Essential and Opposite Roles of ARID1A in Controlling Human Cardiogenesis and Neurogenesis from Pluripotent Stem Cells

2020 ◽  
Author(s):  
Juli Liu ◽  
Sheng Liu ◽  
Hongyu Gao ◽  
Lei Han ◽  
Xiaona Chu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Brain Development ◽  
Neural Development ◽  
Pluripotent Stem Cells ◽  
Human Heart ◽  
Chromatin Accessibility ◽  
Open Chromatin ◽  
Neurogenic Genes ◽  
Genome Wide ◽  
Early Human

AbstractBackgroundEarly human heart and brain development simultaneously occur during embryogenesis. Notably, in human newborns, congenital heart defects strongly associate with neurodevelopmental abnormalities, suggesting a common gene/complex underlying both cardiogenesis and neurogenesis. However, due to lack of in vivo studies, the molecular mechanisms that govern both early human heart and brain development remain elusive.ResultsHere, we report ARID1A, which is a DNA-binding-subunit of the SWI/SNF epigenetic complex, controls both neurogenesis and cardiogenesis from human embryonic stem cells (hESCs) via employing distinct mechanisms. Knockout of ARID1A (ARID1A-/-) led to spontaneous differentiation of neural cells together with globally enhanced expression of neurogenic genes in undifferentiated hESCs. Additionally, when compared with WT hESCs, cardiac differentiation from ARID1A-/- hESCs was prominently suppressed, whereas neural differentiation was significantly promoted. Whole genome-wide scRNA-seq, ATAC-seq, and ChIP-seq analyses revealed that ARID1A was required to open chromatin accessibility on promoters of essential cardiogenic genes, and temporally associated with key cardiogenic transcriptional factors T and MEF2C during early cardiac development. However, during early neural development, transcription of most essential neurogenic genes was dependent on ARID1A, which could interact with a known neural restrictive silencer factor REST/NRSF.ConclusionsWe uncovered the opposite roles by ARID1A to govern both early cardiac and neural development from pluripotent stem cells. Global chromatin accessibility on cardiogenic genes is dependent on ARID1A, whereas transcriptional activity of neurogenic genes is under control by ARID1A, possibly through ARID1A-REST/NRSF interaction.

scholarly journals Reconstructing human early embryogenesis in vitro with pluripotent stem cells

2021 ◽  
Author(s):  
Berna Sozen ◽  
Victoria Jorgensen ◽  
Meng Zhu ◽  
Tongtong Cui ◽  
Magdalena Zernicka-Goetz
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Human Development ◽  
Pluripotent Stem Cells ◽  
Molecular Mechanisms ◽  
Early Embryo ◽  
Human Stem Cells ◽  
Amniotic Cavity ◽  
Early Human

ABSTRACTUnderstanding human development is of fundamental biological and clinical importance. Yet despite its significance, insights into early developmental events in humans still remain largely unknown. While recent advances show that stem cells can mimic embryogenesis1–9 to unravel hidden developmental mechanisms, a stem cell-based model of early human embryogenesis is lacking. Here, we use human extended pluripotent stem cells10to reconstitute early human development in 3-dimensions and recapitulate early embryo-like events. We first perform a systematic characterisation to reveal unique signalling requirements for building the human pre-implantation blastocyst. Further, we show that these in vitro stem cell-derived blastocyst-like structures are able to undertake spatiotemporal self-organisation to mimic peri-implantation remodelling in which a polarised rosette opens up the amniotic cavity within a developing disc. The hallmarks of human early development displayed by this stem cell-based in vitro model mimics features of embryonic day 3 to day 9/10 of natural development. Thus, this platform represents a tractable model system to contribute to the basic understanding of cellular and molecular mechanisms governing early embryonic events in humans and to provide valuable insights into the design of differentiation protocols for human stem cells in clinical applications.

scholarly journals In Vivo Generation of Neural Tumors from Neoplastic Pluripotent Stem Cells Models Early Human Pediatric Brain Tumor Formation

Stem Cells ◽  
2012 ◽  
Vol 30 (3) ◽  
pp. 392-404 ◽  
Author(s):  
Tamra E. Werbowetski-Ogilvie ◽  
Ludivine Coudière Morrison ◽  
Aline Fiebig-Comyn ◽  
Mickie Bhatia
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Pluripotent Stem Cells ◽  
Pediatric Brain Tumor ◽  
Tumor Formation ◽  
Pediatric Brain ◽  
Early Human

scholarly journals A protocol for the generation of blastocyst-like structures from human pluripotent stem cells

2021 ◽  
Author(s):  
Leqian Yu ◽  
Yulei Wei ◽  
Daniel A. Schmitz ◽  
Masahiro Sakurai ◽  
Jun Wu
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
3D Model ◽  
Human Pluripotent Stem Cells ◽  
Developmental Defects ◽  
Human Blastocyst ◽  
Early Human Development ◽  
Early Developmental ◽  
Early Human

Abstract The recent development of stem-cell-based embryo models open new avenues for studying early development in vitro, including humans1. Here we report a protocol for the generation of human blastocyst-like structures from naïve human pluripotent stem cells (hPSCs). These structures, termed human blastoids, provide an accessible, scalable, versatile, and manipulable 3D model to study early human development, understand early pregnancy loss, and gain insights into early developmental defects.

scholarly journals Generation of hepato-biliary-pancreatic organoid from human pluripotent stem cells

2019 ◽  
Author(s):  
Hiroyuki Koike ◽  
Kentaro Iwasawa ◽  
Takanori Takebe
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Three Dimensional ◽  
Human Pluripotent Stem Cell ◽  
Extrinsic Factor ◽  
Interaction Protocol ◽  
Tissue Interactions ◽  
Early Human

Abstract Organogenesis is a complex and inter-connected process, orchestrated by multiple boundary tissue interactions. Here, we established the protocol of the continuous patterning of hepatic, biliary and pancreatic structures from a three-dimensional culture of human pluripotent stem cell (PSC). The boundary interactions between anterior and posterior gut spheroids differentiated from human PSCs enables autonomous emergence of hepato-biliary-pancreatic (HBP) organ domains in the absence of extrinsic factor supply. This anterior-poterior gut interaction protocol can be used to model the early human HBP organogenesis process in vitro.

scholarly journals Silencing of E-cadherin in induced human pluripotent stem cells promotes extraembryonic fates accompanying multilineage differentiation

2020 ◽  
Author(s):  
Ashley RG Libby ◽  
Ivana Vasic ◽  
David A Joy ◽  
Martina Z Krakora ◽  
Fredrico N Mendoza-Camacho ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Human Embryos ◽  
List Type ◽  
Cell Fates ◽  
Cell Adhesions ◽  
Early Human ◽  
Cell Cell

Summary/AbstractIn embryonic development, symmetry breaking events and the mechanical milieus in which they occur coordinate the specification of separate cell lineages. Here, we use 3D aggregates of human pluripotent stem cells (hPSCs) encapsulated in alginate microbeads to model the early blastocyst prior to zona pellucida hatching. We demonstrate that 3D confinement combined with modulation of cell-cell adhesions is sufficient to drive differentiation and collective migration reminiscent of the pre-implantation embryo. Knockdown of the cell adhesion protein CDH1 in encapsulated hPSC aggregates resulted in protrusion morphologies and emergence of extra-embryonic lineages, whereas unencapsulated CDH1(-) aggregates displayed organized radial delamination and mesendoderm specification bias. Transcriptomic similarities between single-cell RNA-sequencing data of early human embryos and encapsulated CDH1(-) aggregates establishes this in vitro system as a competent surrogate for studying early embryonic fate decisions and highlights the relationship between cell-cell adhesions and the mechanical microenvironment in directing cell fate and behavior.HighlightsGeneration of embryonic scale 3D morphogenesis using hydrogel encapsulationManipulating adhesion triggers emergence of specific morphologies and cell fatesAcquisition of germ layer cell fates mimics early human embryonic diversity

Directed differentiation of mouse-induced pluripotent stem cells generates dopaminergic nerve

2010 ◽  
Vol 34 (8) ◽  
pp. S36-S36
Author(s):  
Ping Duan ◽  
Xuelin Ren ◽  
Wenhai Yan ◽  
Xuefei Han ◽  
Xu Yan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Directed Differentiation ◽  
Induced Pluripotent
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