The acetyllysine reader BRD3R promotes human nuclear reprogramming and regulates mitosis

Shao, Zhicheng; Zhang, Ruowen; Khodadadi‐Jamayran, Alireza; Chen, Bin; Crowley, Michael R.; Festok, Muhamad A.; Crossman, David K.; Townes, Tim M.; Hu, Kejin

doi:10.1038/ncomms10869

Cited by 28 publications

(43 citation statements)

References 61 publications

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“…Third, overexpression of the acetyllysine reader BRD3R has been shown to increase reprogramming efficiency in human cells (Shao et al, ). Genes upregulated by BRD3R are associated with mitosis promoting proliferation at early stages of reprogramming (Shao et al, ). Similar to TP53 knockdown, overexpression of BRD3R in BEFs did not have any effect on reprogramming efficiency.…”

Section: Discussionmentioning

confidence: 99%

“…Lentiviral vectors used were: pHAGE-hSTEMCCA (Sommer et al, 2009), pSIN4-EF2-hOSKIM (Ross et al, 2010), and pLM-fSV2A (hOSKM) (Papapetrou et al, 2011) that encode polycistronic hOCT4, hSOX2, hcMYC and hKLF4, pLenti-EF1α-GFP, pLenti-EF1α-hNANOG, pLVH-EF1α-BRD3R (Shao et al, 2016), pLKO.1-shMBD3, pLKO.1-shTP53, and pLenti-CMV-bmiR302/367. Retroviral vectors used were: pMXs-GFP, pMXs-bOCT4, pMXs-bSOX2, pMXs-bKLF4, pMXs-bcMYC, and pMXS-bNANOG.…”

Section: Virus Productionmentioning

confidence: 99%

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Induced pluripotent stem cell generation from bovine somatic cells indicates unmet needs for pluripotency sustenance

Pillai

Kei

Reddy

et al. 2019

Animal Science Journal

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Mechanisms that direct reprogramming of differentiated somatic cells to induced pluripotent stem cells (iPSCs), albeit incomplete in understanding, are highly conserved across all mammalian species studied. Equally, proof of principle that iPSCs can be derived from domestic cattle has been reported in several publications. In our efforts to derive and study bovine iPSCs, we encountered inadequacy of methods to generate, sustain, and characterize these cells. Our results suggest that iPSC protocols optimized for mouse and human somatic cells do not effectively translate to bovine somatic cells, which show some refractoriness to reprogramming that also affects sustenance. Moreover, methods that enhance reprogramming efficiency in mouse and human cells had no effect on improving bovine cell reprogramming. Although use of retroviral vectors coding for bovine OCT4, SOX2, KLF4, cMYC, and NANOG appeared to produce consistent iPSC‐like cells from both fibroblasts and cells from the Wharton's jelly, these colonies could not be sustained. Use of bovine genes could successfully reprogram both mouse and human cells. These findings indicated either incomplete reprogramming and/or discordant/inadequate culture conditions for bovine pluripotent stem cells. Therefore, additional studies that advance core knowledge of bovine pluripotency are necessary before any anticipated iPSC‐driven bovine technologies can be realized.

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Section: Discussionmentioning

confidence: 99%

Section: Virus Productionmentioning

confidence: 99%

Induced pluripotent stem cell generation from bovine somatic cells indicates unmet needs for pluripotency sustenance

Pillai

Kei

Reddy

et al. 2019

Animal Science Journal

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“…All the reads from our RNA-seq (GSE66798) [26] and the reads from the experiments GSE71645 [27], GSE59528 [28] and GSE36552 [47] were mapped to the human reference genome (GRCh37/hg19) using the STAR aligner [29] guided by a gene transfer file (Ensembl GTF version GRCh37.70).…”

Section: Bioinformaticsmentioning

confidence: 99%

The Universal 3D3 Antibody of Human PODXL Is Pluripotent Cytotoxic, and Identifies a Residual Population After Extended Differentiation of Pluripotent Stem Cells

Kang

Yao

Khodadadi‐Jamayran

et al. 2016

Stem Cells and Development

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Podocalyxin-like protein (PODXL) is a member of CD34 family proteins. It is the protein that carries many post-translational epitopes responsible for various pluripotent surface markers including TRA-1-60, TRA-1-81, GCTM2, GP200, and mAb84. However, PODXL has not attracted the attention of stem cell biologists. Here, we report several features of PODXL mRNA and protein in pluripotent stem cells. Similar to the modificationdependent pluripotent epitopes, PODXL transcripts and carrier protein are also features of pluripotency. PODXL is highly expressed in early human embryos from oocytes up to four-cell stages. During reprogramming of human cells to pluripotency, in contrast to TRA-1-60 and TRA-1-81, PODXL is activated by KLF4 at a very early time of reprogramming. Although TRA-1-60 and TRA-1-81 are completely lost upon differentiation, a residual PODXL + population exists even after extended differentiation and they were identified by the universal human PODXL epitope 3D3. Unlike TRA-1-60 and TRA-1-81 epitopes that are unique to primate pluripotent stem cells (PSCs), PODXL carrier protein can be used as a murine surface marker. Most importantly, antibody to 3D3 epitope causes massive necrosis and apoptosis of human PSCs (hPSCs). We suggest that 3D3 antibody could be employed to eliminate the tumorigenic pluripotent cells in hPSC-derived cells for cell transplantation.

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“…Conversion of fibroblasts into iPSCs involves dramatic changes in cell morphology and establishes a unique cellular colony characteristic of PSC culture. In fact, high quality iPS cell lines can be established by selecting colonies with the characteristic cell and colony morphology without a reporter [7,8,20], and automatic imaging system can be used for identification of high quality iPSC colonies [21]. GO analyses of reprogramome reveal that 22 and 23 such GO terms are associated with the downreprogramome and upreprogramome, respectively (Table S6).…”

Section: Profiling and Quantification Of Reprogramming In Cell Morphomentioning

confidence: 99%

“…iPSC reprogramming from human fibroblasts is a prolonged and stochastic process with a very low efficiency [4][5][6]. One reason for this inefficient conversion of cell fates is probably the great expanse of reprogramming required [7,8]. Although it is considered to be extensive as well as intensive, the degree of iPSC reprogramming has not been determined quantitatively.…”

Section: Introductionmentioning

confidence: 99%

Profiling of the reprogramome and quantification of fibroblast reprogramming to pluripotency

Ianov

Crossman

2020

Preprint

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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 that need to be reprogrammed to the expression levels found in pluripotent stem cells (PSCs). This concept in combination with RNAseq 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 have to be extensively and intensely reprogrammed for the establishment of pluripotency. We further developed the first 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.

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The acetyllysine reader BRD3R promotes human nuclear reprogramming and regulates mitosis

Cited by 28 publications

References 61 publications

Induced pluripotent stem cell generation from bovine somatic cells indicates unmet needs for pluripotency sustenance

Induced pluripotent stem cell generation from bovine somatic cells indicates unmet needs for pluripotency sustenance

The Universal 3D3 Antibody of Human PODXL Is Pluripotent Cytotoxic, and Identifies a Residual Population After Extended Differentiation of Pluripotent Stem Cells

Profiling of the reprogramome and quantification of fibroblast reprogramming to pluripotency

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