An organoid and multi-organ developmental cell atlas reveals multilineage fate specification in the human intestine

Human intestinal organoids (HIOs) generated from pluripotent stem cells provide extraordinary opportunities to explore development and disease. Here, we generate a single-cell transcriptome reference atlas from HIOs and from multiple developing human organs to quantify the specificity of HIO cell fate acquisition, and to explore alternative fates. We identify epithelium-mesenchyme interactions, transcriptional regulators involved in cell fate specification, and stem cell maturation features in the primary tissue that are recapitulated in HIOs. We use an HIO time course to reconstruct the molecular dynamics of intestinal stem cell emergence, as well as the specification of multiple mesenchyme subtypes. We find that the intestinal master regulator CDX2 correlates with distinct phases of epithelial and mesenchymal development, and CDX2 deletion perturbs the differentiation of both intestinal epithelium and mesenchyme. Collectively our data provides a comprehensive and quantitative assessment of HIO development, and illuminates the molecular machinery underlying endodermal and mesodermal cell fate specification.

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Stem Cell Fate Specification: Role of Master Regulatory Switch Transcription Factor PU.1 in Differential Hematopoiesis

Stem Cells and Development ◽

10.1089/scd.2005.14.140 ◽

2005 ◽

Vol 14 (2) ◽

pp. 140-152 ◽

Cited By ~ 31

Author(s):

Gurudutta U. Gangenahalli ◽

Pallavi Gupta ◽

Daman Saluja ◽

Yogesh K. Verma ◽

Vimal Kishore ◽

...

Keyword(s):

Transcription Factor ◽

Stem Cell ◽

Cell Fate ◽

Cell Fate Specification ◽

Stem Cell Fate ◽

Fate Specification

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Molecular Mechanisms of Stem Cell Pluripotency and Cell Fate Specification

Journal of Molecular Biology ◽

10.1016/j.jmb.2017.03.011 ◽

2017 ◽

Vol 429 (10) ◽

pp. 1439-1440

Author(s):

Greg M. Findlay ◽

Laurent David ◽

Tobias A. Beyer

Keyword(s):

Stem Cell ◽

Cell Fate ◽

Molecular Mechanisms ◽

Cell Fate Specification ◽

Fate Specification ◽

Stem Cell Pluripotency

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Regulation of intestinal stem cell fate specification

Science China Life Sciences ◽

10.1007/s11427-015-4859-7 ◽

2015 ◽

Vol 58 (6) ◽

pp. 570-578 ◽

Cited By ~ 9

Author(s):

Zhen Qi ◽

Ye-Guang Chen

Keyword(s):

Stem Cell ◽

Cell Fate ◽

Intestinal Stem Cell ◽

Cell Fate Specification ◽

Stem Cell Fate ◽

Fate Specification

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Differential Network Analysis Reveals Regulatory Patterns in Neural Stem Cell Fate Decision

10.21203/rs.2.19445/v1 ◽

2019 ◽

Author(s):

Jiang Xie ◽

Fuzhang yang ◽

Jiamin Sun ◽

Jiao Wang

Keyword(s):

Stem Cell ◽

Single Cell ◽

Cell Fate ◽

Neural Stem Cell ◽

Integrative Analysis ◽

Cell Fate Decisions ◽

Multi Stage ◽

Gene Regulatory ◽

Cell Transcriptome ◽

Single Cell Transcriptome

Abstract Background Neural stem cell (NSC) differentiation is one of many multi-stage lineage systems that require multiple cell fate decisions. Recent single-cell transcriptome datasets became available at individual differentiation, however, a systematic and integrative analysis of multiple datasets at multiple temporal points of NSC differentiation is lacking. Results Here we investigate five NSC differentiation paths by analyzing and comparing four different single-cell transcriptome datasets. By constructing gene regulatory networks for each cell type, we delineate their regulatory patterns via analyses of differential topology and network diffusion. Among the five NSC differentiation paths, we find 12 common differentially expressed genes, with one common three-gene regulatory pattern shared by all paths. The identified regulatory pattern, partly supported by previous experimental evidence, is found to be essential to all differentiation paths, however, plays a different role in each path when regulating other genes. Conclusions Together, our integrative analysis provides both common and specific regulatory mechanisms for each of the five NSC differentiation paths, and the approach can be applied to analyzing other complex multi-stage lineage systems.

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Hes5.9 Coordinate FGF and Notch Signaling to Modulate Gastrulation via Regulating Cell Fate Specification and Cell Migration in Xenopus tropicalis

Genes ◽

10.3390/genes11111363 ◽

2020 ◽

Vol 11 (11) ◽

pp. 1363

Author(s):

Xiao Huang ◽

Liyue Zhang ◽

Shanshan Yang ◽

Yongpu Zhang ◽

Mingjiang Wu ◽

...

Keyword(s):

Cell Migration ◽

Notch Signaling ◽

Signaling Pathways ◽

Cell Fate ◽

Expression Patterns ◽

Marker Genes ◽

Cell Fate Specification ◽

Mesodermal Cell ◽

Cell Fate Decisions ◽

Fate Specification

Gastrulation drives the establishment of three germ layers and embryonic axes during frog embryonic development. Mesodermal cell fate specification and morphogenetic movements are vital factors coordinating gastrulation, which are regulated by numerous signaling pathways, such as the Wnt (Wingless/Integrated), Notch, and FGF (Fibroblast growth factor) pathways. However, the coordination of the Notch and FGF signaling pathways during gastrulation remains unclear. We identified a novel helix–loop–helix DNA binding domain gene (Hes5.9), which was regulated by the FGF and Notch signaling pathways during gastrulation. Furthermore, gain- and loss-of-function of Hes5.9 led to defective cell migration and disturbed the expression patterns of mesodermal and endodermal marker genes, thus interfering with gastrulation. Collectively, these results suggest that Hes5.9 plays a crucial role in cell fate decisions and cell migration during gastrulation, which is modulated by the FGF and Notch signaling pathways.

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Castor is required for Hedgehog-dependent cell-fate specification and follicle stem cell maintenance in Drosophila oogenesis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1300725110 ◽

2013 ◽

Vol 110 (19) ◽

pp. E1734-E1742 ◽

Cited By ~ 35

Author(s):

Y.-C. Chang ◽

A. C.- C. Jang ◽

C.-H. Lin ◽

D. J. Montell

Keyword(s):

Stem Cell ◽

Cell Fate ◽

Cell Fate Specification ◽

Drosophila Oogenesis ◽

Fate Specification ◽

Stem Cell Maintenance ◽

Dependent Cell ◽

Cell Maintenance

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Defining Epidermal Stem Cell Fate Infidelity and Immunogenicity in Hidradenitis Suppurativa at the Single-Cell Resolution

10.1101/2020.04.21.053611 ◽

2020 ◽

Author(s):

Meaghan Marohn ◽

Meng-ju Lin ◽

Wei-wen Yu ◽

Ciara Mae Mendoza ◽

Juliana Remark ◽

...

Keyword(s):

Stem Cell ◽

Single Cell ◽

Cell Fate ◽

Hidradenitis Suppurativa ◽

Unique Feature ◽

Inflammatory Skin Disease ◽

Stem Cell Fate ◽

Apocrine Sweat Gland ◽

Cell Transcriptome ◽

Single Cell Transcriptome

AbstractHidradenitis suppurativa (HS) is a severe chronic inflammatory skin disease affecting human apocrine sweat gland-bearing skin regions. One unique feature of HS is the development of keratinized sinus tracts that grow extensively deep in the dermis and are highly immunogenic. Here, we demonstrated that the stem cell fate infidelity exists in the HS sinus tracts, which exhibit features of both surface epidermis and appendages. Using single cell transcriptome analyses, we finely dissected different compartments of the HS epithelium and identified their respective changes in cytokine expression during disease progression and the critical interactions with the immune cells. Together, our work provides advanced understanding of the pathological epidermal remodeling and important implications for HS therapeutics.

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