Profiling and quantification of pluripotency reprogramming reveal that WNT pathways and cell morphology have to be reprogramed extensively
Pluripotent state can be established via reprogramming of somatic nuclei by factors within an oocyte or by ectopic expression of a few transgenes. Considered as being extensive and intensive, the full complement of genes to be reprogrammed, however, has never been defined, nor has the degree of repr...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-05-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844020308793 |
| _version_ | 1819057684117192704 |
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| author | Kejin Hu Lara Ianov David Crossman |
| author_facet | Kejin Hu Lara Ianov David Crossman |
| author_sort | Kejin Hu |
| collection | DOAJ |
| description | Pluripotent state can be established via reprogramming of somatic nuclei by factors within an oocyte or by ectopic expression of a few transgenes. Considered as being extensive and intensive, the full complement of genes to be reprogrammed, however, has never been defined, nor has the degree of reprogramming been determined quantitatively. Here, we propose a new concept of reprogramome, which is defined as the full complement of genes to be reprogrammed to the expression levels found in pluripotent stem cells (PSCs). This concept in combination with RNA-seq enables us to precisely profile reprogramome and sub-reprogramomes, and study the reprogramming process with the help of other available tools such as GO analyses. With reprogramming of human fibroblasts into PSCs as an example, we have defined the full complement of the human fibroblast-to-PSC reprogramome. Furthermore, our analyses of the reprogramome revealed that WNT pathways and genes with roles in cellular morphogenesis should be extensively and intensely reprogrammed for the establishment of pluripotency. We further developed a new mathematical model to quantitate the overall reprogramming, as well as reprogramming in a specific cellular feature such as WNT signaling pathways and genes regulating cellular morphogenesis. We anticipate that our concept and mathematical model may be applied to study and quantitate other reprogramming (pluripotency reprogramming from other somatic cells, and lineage reprogramming), as well as transcriptional and epigenetic differences between any two types of cells including cancer cells and their normal counterparts. |
| first_indexed | 2024-12-21T13:43:13Z |
| format | Article |
| id | doaj.art-31fd3eb9068149aa8d1255697bbc95c2 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-12-21T13:43:13Z |
| publishDate | 2020-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-31fd3eb9068149aa8d1255697bbc95c22022-12-21T19:01:57ZengElsevierHeliyon2405-84402020-05-0165e04035Profiling and quantification of pluripotency reprogramming reveal that WNT pathways and cell morphology have to be reprogramed extensivelyKejin Hu0Lara Ianov1David Crossman2Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Corresponding author.Civitan International Research Center, University of Alabama at Birmingham, Birmingham, AL, 35294, USAHeflin Center for Genomic Sciences, University of Alabama at Birmingham, Birmingham, AL, 35294, USAPluripotent state can be established via reprogramming of somatic nuclei by factors within an oocyte or by ectopic expression of a few transgenes. Considered as being extensive and intensive, the full complement of genes to be reprogrammed, however, has never been defined, nor has the degree of reprogramming been determined quantitatively. Here, we propose a new concept of reprogramome, which is defined as the full complement of genes to be reprogrammed to the expression levels found in pluripotent stem cells (PSCs). This concept in combination with RNA-seq enables us to precisely profile reprogramome and sub-reprogramomes, and study the reprogramming process with the help of other available tools such as GO analyses. With reprogramming of human fibroblasts into PSCs as an example, we have defined the full complement of the human fibroblast-to-PSC reprogramome. Furthermore, our analyses of the reprogramome revealed that WNT pathways and genes with roles in cellular morphogenesis should be extensively and intensely reprogrammed for the establishment of pluripotency. We further developed a new mathematical model to quantitate the overall reprogramming, as well as reprogramming in a specific cellular feature such as WNT signaling pathways and genes regulating cellular morphogenesis. We anticipate that our concept and mathematical model may be applied to study and quantitate other reprogramming (pluripotency reprogramming from other somatic cells, and lineage reprogramming), as well as transcriptional and epigenetic differences between any two types of cells including cancer cells and their normal counterparts.http://www.sciencedirect.com/science/article/pii/S2405844020308793Biological sciencesCell biologySystems biologyMathematical biosciencesBioinformaticsTranscriptomics |
| spellingShingle | Kejin Hu Lara Ianov David Crossman Profiling and quantification of pluripotency reprogramming reveal that WNT pathways and cell morphology have to be reprogramed extensively Heliyon Biological sciences Cell biology Systems biology Mathematical biosciences Bioinformatics Transcriptomics |
| title | Profiling and quantification of pluripotency reprogramming reveal that WNT pathways and cell morphology have to be reprogramed extensively |
| title_full | Profiling and quantification of pluripotency reprogramming reveal that WNT pathways and cell morphology have to be reprogramed extensively |
| title_fullStr | Profiling and quantification of pluripotency reprogramming reveal that WNT pathways and cell morphology have to be reprogramed extensively |
| title_full_unstemmed | Profiling and quantification of pluripotency reprogramming reveal that WNT pathways and cell morphology have to be reprogramed extensively |
| title_short | Profiling and quantification of pluripotency reprogramming reveal that WNT pathways and cell morphology have to be reprogramed extensively |
| title_sort | profiling and quantification of pluripotency reprogramming reveal that wnt pathways and cell morphology have to be reprogramed extensively |
| topic | Biological sciences Cell biology Systems biology Mathematical biosciences Bioinformatics Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2405844020308793 |
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