Models of global gene expression define major domains of cell type and tissue identity

Hutchins, Andrew P.; Yang, Zhongzhou; Li, Yuhao; He, Fengjiao; Fu, Xiaozhe; Wang, Xiaoshan; Li, Dongwei; Liu, Kairong; He, Jiangping; Wang, Yong; Chen, Jiekai; Esteban, Miguel A.; Pei, Duanqing

doi:10.1093/nar/gkx054

Cited by 53 publications

(82 citation statements)

References 75 publications

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“…We compared our data to a comprehensive atlas of murine cell types ( 26 ). We applied ICA to decompose expression of the atlas of cell types into 120 mutually independent components, and we correlated these to the components extracted from our single cell data (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…We compared our data to a comprehensive atlas of murine cell types from( 26 ) that consists of uniformly re-analysed bulk and single cell RNA-seq data from 113 publications including 921 biological samples consisting of 272 distinct cell types.…”

Section: Methodsmentioning

confidence: 99%

“…Reprogramming efficiency data for different hematopoietic cell types as well as from mouse tail fibroblasts are from reference ( 18 ); for neural stem cells, pancreatic beta cells, keratinocytes and MEFs are from references ( 20 ) ( 19 ) ( 17 ) and ( 2 ), respectively. Cell reprogramming efficiencies were matched to the expression values of their Myc component, obtained from the mouse cell atlas ( 26 ) as described above (Fig. S2A, C)…”

Section: Methodsmentioning

confidence: 99%

“… A, Distribution of gene expression similarity between single cells and reference bone marrow derived macrophages( 26 ) (acquisition of macrophage state) during transdifferentiation. B, Correlation between the Myc targets component and acquisition of macrophage state from A .…”

Section: Main Textmentioning

confidence: 99%

“… A, Heatmap of the correlations between the gene loadings of selected single cell independent components and gene loadings of selected independent components from the reference mouse cell atlas( 26 ). B , Distribution of the single cell projections onto the macrophage, mid pluripotency, granulocyte, monocyte, pre-B, late pluripotency, G2/M, oxidative phosphorylation, G1/S and a second oxidative phosphorylation specific components across time points.…”

Section: Supplementary Materialsmentioning

confidence: 99%

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Single cell expression analysis uncouples transdifferentiation and reprogramming

Francesconi

Stefano

Berenguer

et al. 2018

Preprint

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25Many somatic cell types are plastic, having the capacity to convert into other 26 specialized cells (transdifferentiation)(1) or into induced pluripotent stem cells (iPSCs, 27 reprogramming)(2) in response to transcription factor over--expression. To explore 28 what makes a cell plastic and whether these different cell conversion processes are 29 coupled, we exposed bone marrow derived pre--B cells to two different transcription 30 factor overexpression protocols that efficiently convert them either into macrophages 31 or iPSCs and monitored the two processes over time using single cell gene expression 32 analysis. We found that even in these highly efficient cell fate conversion systems, 33 cells differ in both their speed and path of transdifferentiation and reprogramming. 34This heterogeneity originates in two starting pre--B cell subpopulations, large pre--BII 35 and the small pre--BII cells they normally differentiate into. The large cells 36 transdifferentiate slowly but exhibit a high efficiency of iPSC reprogramming. In 37 contrast, the small cells transdifferentiate rapidly but are highly resistant to 38reprogramming. Moreover, the large B cells induce a stronger transient 39 granulocyte/macrophage progenitor (GMP)--like state, while the small B cells undergo a 40 more direct conversion to the macrophage fate. The large cells are cycling and exhibit 41high Myc activity whereas the small cells are Myc low and mostly quiescent. The 42 observed heterogeneity of the two cell conversion processes can therefore be traced 43to two closely related cell types in the starting population that exhibit different types 44 of plasticity. These data show that a somatic cell's propensity for either 45 transdifferentiation and reprogramming can be uncoupled. 46 47

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

Section: Supplementary Materialsmentioning

confidence: 99%

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Single cell expression analysis uncouples transdifferentiation and reprogramming

Francesconi

Stefano

Berenguer

et al. 2018

Preprint

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Opiate Receptors

Zheng¹,

Law²,

Loh³

2020

Encyclopedia of Life Sciences

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Morphine and its congeners are considered to be the best painkilling agents available. The molecular basis for the observed analgesics effects and other pharmacological functions of opioid analgesic drugs are defined by multiple opioid receptors. The opioid receptors are typical G protein‐coupled receptors and activate a variety of downstream signalling pathways via G protein‐ or β‐arrestin‐dependent pathway. Because of the existence of multiple endogenous peptide ligands and the crosstalk with other nonreceptor signalling pathways or neurological circuitries, the pharmacological functions mediated by the multiple opioid receptors are quite complex and are involved in multiple physiological processes, such as the effects on the functions of immune cells and neural stem cells. Key Concepts The molecular basis for the observed pharmacological functions of opioid analgesic drugs is defined by multiple opioid receptors. Signalling transduction from opioid receptors is essential for the functions of opioids. As classical GPCR, agonist‐selective signalling can be observed with opioid receptors. Opioid analgesic drugs and opioid receptors contribute to other CNS functions in addition to pain relief. The observed pharmacological functions of opioid analgesic drugs involve nonreceptor elements.

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Diversity among POU transcription factors in chromatin recognition and cell fate reprogramming

Malik¹,

Zimmer²,

Jauch³

2018

Cell. Mol. Life Sci.

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The POU (Pit-Oct-Unc) protein family is an evolutionary ancient group of transcription factors (TFs) that bind specific DNA sequences to direct gene expression programs. The fundamental importance of POU TFs to orchestrate embryonic development and to direct cellular fate decisions is well established, but the molecular basis for this activity is insufficiently understood. POU TFs possess a bipartite 'two-in-one' DNA binding domain consisting of two independently folding structural units connected by a poorly conserved and flexible linker. Therefore, they represent a paradigmatic example to study the molecular basis for the functional versatility of TFs. Their modular architecture endows POU TFs with the capacity to accommodate alternative composite DNA sequences by adopting different quaternary structures. Moreover, associations with partner proteins crucially influence the selection of their DNA binding sites. The plentitude of DNA binding modes confers the ability to POU TFs to regulate distinct genes in the context of different cellular environments. Likewise, different binding modes of POU proteins to DNA could trigger alternative regulatory responses in the context of different genomic locations of the same cell. Prominent POU TFs such as Oct4, Brn2, Oct6 and Brn4 are not only essential regulators of development but have also been successfully employed to reprogram somatic cells to pluripotency and neural lineages. Here we review biochemical, structural, genomic and cellular reprogramming studies to examine how the ability of POU TFs to select regulatory DNA, alone or with partner factors, is tied to their capacity to epigenetically remodel chromatin and drive specific regulatory programs that give cells their identities.

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Models of global gene expression define major domains of cell type and tissue identity

Cited by 53 publications

References 75 publications

Single cell expression analysis uncouples transdifferentiation and reprogramming

Single cell expression analysis uncouples transdifferentiation and reprogramming

Opiate Receptors

Diversity among POU transcription factors in chromatin recognition and cell fate reprogramming

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