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Thrombopoietin knock-in augments platelet generation from human embryonic stem cells

Overview of attention for article published in Stem Cell Research & Therapy, July 2018
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Title
Thrombopoietin knock-in augments platelet generation from human embryonic stem cells
Published in
Stem Cell Research & Therapy, July 2018
DOI 10.1186/s13287-018-0926-x
Pubmed ID
Authors

Leisheng Zhang, Cuicui Liu, Hongtao Wang, Dan Wu, Pei Su, Mengge Wang, Jiaojiao Guo, Shixuan Zhao, Shuxu Dong, Wen Zhou, Cameron Arakaki, Xiaobing Zhang, Jiaxi Zhou

Abstract

Refinement of therapeutic-scale platelet production in vitro will provide a new source for transfusion in patients undergoing chemotherapy or radiotherapy. However, procedures for cost-effective and scalable platelet generation remain to be established. In this study, we established human embryonic stem cell (hESC) lines containing knock-in of thrombopoietin (TPO) via CRISPR/Cas9-mediated genome editing. The expression and secretion of TPO was detected by western blotting and enzyme-linked immunosorbent assay. Then, we tested the potency for hematopoietic differentiation by coculturing the cells with mAGM-S3 cells and measured the generation of CD43+ and CD45+ hematopoietic progenitor cells (HPCs). The potency for megakaryocytic differentiation and platelet generation of TPO knock-in hESCs were further detected by measuring the expression of CD41a and CD42b. The morphology and function of platelets were analyzed with electronic microscopy and aggregation assay. The TPO gene was successfully inserted into the AAVS1 locus of the hESC genome and two cell lines with stable TPO expression and secretion were established. TPO knock-in exerts minimal effects on pluripotency but enhances early hematopoiesis and generation of more HPCs. More importantly, upon its knock-in, TPO augments megakaryocytic differentiation and platelet generation. In addition, the platelets derived from hESCs in vitro are functionally and morphologically comparable to those found in peripheral blood. Furthermore, TPO knock-in can partially replace the large quantities of extrinsic TPO necessary for megakaryocytic differentiation and platelet generation. Our results demonstrate that autonomous production of cytokines in hESCs may become a powerful approach for cost-effective and large-scale platelet generation in translational medicine.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 11 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 11 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 3 27%
Librarian 1 9%
Other 1 9%
Student > Ph. D. Student 1 9%
Student > Master 1 9%
Other 1 9%
Unknown 3 27%
Readers by discipline Count As %
Agricultural and Biological Sciences 3 27%
Biochemistry, Genetics and Molecular Biology 2 18%
Medicine and Dentistry 2 18%
Nursing and Health Professions 1 9%
Unknown 3 27%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 July 2018.
All research outputs
#11,759,512
of 13,248,851 outputs
Outputs from Stem Cell Research & Therapy
#1,013
of 1,145 outputs
Outputs of similar age
#231,250
of 267,143 outputs
Outputs of similar age from Stem Cell Research & Therapy
#15
of 15 outputs
Altmetric has tracked 13,248,851 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,145 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.4. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 267,143 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 15 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.