AIBP-mediated cholesterol efflux instructs hematopoietic stem and progenitor cell fate

Author:

Gu Qilin1ORCID,Yang Xiaojie1ORCID,Lv Jie12ORCID,Zhang Jiaxiong13,Xia Bo12,Kim Jun-dae1,Wang Ruoyu45ORCID,Xiong Feng4,Meng Shu1,Clements Thomas P.6,Tandon Bhavna6ORCID,Wagner Daniel S.6ORCID,Diaz Miguel F.7,Wenzel Pamela L.7ORCID,Miller Yury I.8,Traver David9,Cooke John P.11011,Li Wenbo45,Zon Leonard I.12ORCID,Chen Kaifu121011ORCID,Bai Yongping3ORCID,Fang Longhou1101113ORCID

Affiliation:

1. Center for Cardiovascular Regeneration, Houston Methodist, 6550 Fannin Street, Houston, TX 77030, USA.

2. Center for Bioinformatics and Computational Biology, Department of Cardiovascular Sciences, Houston Methodist, 6550 Fannin Street, Houston, TX 77030, USA.

3. Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.

4. Department of Biochemistry and Molecular Biology, UTHealth McGovern Medical School, University of Texas MD Anderson Cancer Center and UTHealth Houston, Houston, TX 77030, USA.

5. Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center and UTHealth Houston, Houston, TX 77030, USA.

6. Department of BioSciences, Rice University, Houston, TX 77005, USA.

7. Children’s Regenerative Medicine Program, Department of Pediatric Surgery, Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

8. Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.

9. Division of Biological Sciences, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.

10. Houston Methodist Institute for Academic Medicine, Houston Methodist Research Institute, Houston Methodist, 6550 Fannin Street, Houston, TX 77030, USA.

11. Department of Cardiothoracic Surgeries, Weill Cornell Medical College, Cornell University, Ithaca, NY 10065, USA.

12. Stem Cell Program and Division of Hematology/Oncology, Boston Children’s Hospital and Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.

13. Department of Obstetrics and Gynecology, Houston Methodist, 6550 Fannin Street, Houston, TX 77030, USA.

Abstract

Regulating HSC progenitors via cholesterol Atherosclerosis is characterized by the buildup of cholesterol-containing lipoproteins in the vascular wall. This increased cholesterol augments hematopoietic stem and progenitor cell (HSPC) counts, and the resultant increase in leukocytes is associated with increased cardiovascular disease. Gu et al. describe a mechanism orchestrating HSPC specification from the hemogenic endothelium (HE) during embryogenesis (see the Perspective by Rajan and Berman). ApoA-I binding protein accelerated cholesterol efflux from the HE, activating the transcription factor Srebp2, which in turn transactivated Notch signaling. This mechanism also appears to be important for adult HSPC expansion in hypercholesterolemia. Science , this issue p. 1085 ; see also p. 1041

Funder

National Institutes of Health

National Heart, Lung, and Blood Institute

Cancer Prevention and Research Institute of Texas

American Heart Association

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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