Evidence map›Paper›PMID 30668923›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2019

Lrp5 and Lrp6 are required for maintaining self-renewal and differentiation of hematopoietic stem cells.

Juanjuan Liu, Zhengzhi Cui, Fang Wang, Yingpeng Yao, Guotao Yu, Jingjing Liu, Dengchao Cao, Shuaishuai Niu, Menghao You, Zhen Sun and 6 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.5field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
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  3. Article
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  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. TCF1 in T cell immunity: a broadened frontier.Nature reviews. Immunology · 2022
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
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  18. Article
  19. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 2 institutions in 2 countries.

Juanjuan LiuState Key Laboratory of Agrobiotechnology and, China Agricultural University, Beijing, China.
Zhengzhi CuiState Key Laboratory of Agrobiotechnology and, China Agricultural University, Beijing, China.
Fang WangState Key Laboratory of Agrobiotechnology and, China Agricultural University, Beijing, China.
Yingpeng YaoState Key Laboratory of Agrobiotechnology and, China Agricultural University, Beijing, China.
Guotao YuState Key Laboratory of Agrobiotechnology and, China Agricultural University, Beijing, China.
Jingjing LiuState Key Laboratory of Agrobiotechnology and, China Agricultural University, Beijing, China.
Dengchao CaoState Key Laboratory of Agrobiotechnology and, China Agricultural University, Beijing, China.
Shuaishuai NiuState Key Laboratory of Agrobiotechnology and, China Agricultural University, Beijing, China.
Menghao YouState Key Laboratory of Agrobiotechnology and, China Agricultural University, Beijing, China.
Zhen SunState Key Laboratory of Agrobiotechnology and, China Agricultural University, Beijing, China.
Di LianState Key Laboratory of Agrobiotechnology and, China Agricultural University, Beijing, China.
Tianyan ZhaoState Key Laboratory of Agrobiotechnology and, China Agricultural University, Beijing, China.
Youmin KangState Key Laboratory of Agrobiotechnology and, China Agricultural University, Beijing, China.
Yaofeng ZhaoState Key Laboratory of Agrobiotechnology and, China Agricultural University, Beijing, China.
Hai-Hui XueDepartment of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Shuyang YuState Key Laboratory of Agrobiotechnology and, China Agricultural University, Beijing, China.
China Agricultural University · CNUniversity of Iowa · US

Funding

Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Douglas Robert Spitz · 2000 to 2026
$70.0M
6 · The paper itself

Abstract

Hematopoietic stem cells (HSCs) have the capacity for self-renewal to maintain the HSCs' pool and the ability for multilineage differentiation, which are responsible for sustained production of multiple blood lineages. The regulation of HSC development is controlled precisely by complex signal networks and hematopoietic microenvironment, which has been termed the HSCs' niche. The Wnt signaling pathway is one of a variety of signaling pathways that have been involved in HSC self-renewal and maintenance. Previous studies are indeterminant on the regulation of adult HSCs upon canonical Wnt signaling pathways because of the different experimental systems and models used. In this study, we generated the conditional knockout Wnt coreceptor low-density lipoprotein receptor-related protein 5 (Lrp5) and low-density lipoprotein receptor-related protein 6 (Lrp6) mice in adult hematopoiesis via Vav-Cre Loxp system. Inactivation of Lrp5 and -6 in a hematopoietic system diminished the pool of HSCs, but there were no obvious defects in mature immune cells. Lrp5 and -6 double deficiency HSCs showed intrinsic defects in self-renewal and differentiation due to reduced proliferation and increased quiescence of the cell cycle. Analysis of HSC gene expression suggested that the quiescence regulators were significantly up-regulated, such as Egr1, Cdkn1a, Nr4a1, Gata2, Junb and Btg2, and the positive cell cycle regulators were correspondingly down-regulated, such as Ccna2 and Ranbp1. Taken together, we investigated the roles of Lrp5 and -6 in HSCs by functional and bioinformatic assays, and we demonstrated that Lrp5 and -6 are required for the self-renewal and differentiation of adult HSCs. The canonical Wnt pathway may contribute to maintaining the HSC pool and regulate the differentiation of adult HSCs by controlling cell cycle gene regulatory module.-Liu, J., Cui, Z., Wang, F., Yao, Y., Yu, G., Liu, J., Cao, D., Niu, S., You, M., Sun, Z., Lian, D., Zhao, T., Kang, Y., Zhao, Y., Xue, H.-H., Yu, S. Lrp5 and Lrp6 are required for maintaining self-renewal and differentiation of hematopoietic stem cells.

Indexed as

AnimalsCell CycleCell DifferentiationDown-RegulationHematopoiesisHematopoietic Stem CellsLow Density Lipoprotein Receptor-Related Protein-5Low Density Lipoprotein Receptor-Related Protein-6MiceStem Cell NicheWnt ProteinsWnt Signaling PathwayLow Density Lipoprotein Receptor-Related Protein-5Low Density Lipoprotein Receptor-Related Protein-6Lrp5 protein, mouseLrp6 protein, mouseWnt Proteinscell cycledevelopmentlineagereconstitutionWnt signaling

Identifiers

PMID30668923
PMCPMC6988868
OpenAlexW2914001275

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.