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Stem cell biology

FAM122A is required for hematopoietic stem cell function

Leukemia volume 35, pages 2130–2134 (2021)Cite this article

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The homeostasis of hematopoietic stem cell (HSC) is critical for maintaining whole blood system throughout the entire organism life span, in which HSCs keep the balance of quiescence, self-renewal, differentiation, and apoptosis through a tight regulation of intrinsic and extrinsic signaling pathways [1]. More than 70% HSCs are in the quiescent G0 stage, since a dormant status is necessary to preserve their self-renewal capacities and prevent stem cell exhaustion [2, 3]. In response to blood cell loss or other stress stimulation, HSCs may rapidly enter cycling and replenish the hematopoietic system [4].

Family with sequence similarity 122A (FAM122A) is a human housekeeping gene, localized on chromosome 9q21.1 within the first intron of PIP5K1B (phosphatidylinositol 4-phosphate 5-kinase) gene. It has 287 amino acids with highly conserved in many species of mammary animals. Previously we reported that FAM122A is an inhibitor of protein phosphatase 2A [5], and more recently, FAM122A has been found to be abnormally upregulated in acute myeloid leukemia (AML) characterized with the dysfunction of myeloid stem cells [6], and is essential for maintaining the growth of AML cells in vitro cultured cells and in vivo AML cell engraftment [7]. In this study, we investigated whether FAM122A has a role in the function of HSCs.

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Fig. 1: Fam122a deletion promotes quiescent LT-HSC into cycling.
Fig. 2: Fam122a deletion compromises the long-term repopulation capacity of HSCs.

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Acknowledgements

This study was supported by the grants from Chinese National Natural Science Foundation (81572290 and 32070720 from YH; 81830091, 91853206 and 81972583 from GQC) and its innovative group support (81721004 from GQC),  CAMS Innovation Fund for Medical Sciences (CIFMS) (2019-I2M-5-051) as well as the Fundamental Research Funds for the Central Universities.

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  1. Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education and Chinese Academy of Medical Sciences Research Unit (NO.2019RU043), Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China

    Man-Hua Liu, Xiao-Cui Zhang, Jing Chen, Yun-Sheng Yang, Yin-Qi Wang, Jun-Ke Zheng, Guo-Qiang Chen & Ying Huang

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  1. Man-Hua Liu
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Correspondence to Guo-Qiang Chen or Ying Huang.

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Liu, MH., Zhang, XC., Chen, J. et al. FAM122A is required for hematopoietic stem cell function. Leukemia 35, 2130–2134 (2021). https://doi.org/10.1038/s41375-020-01099-9

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