Ph.D.Supervisor

Email: yanni_ma@126.com; mayanni@ibms.cams.cn

Phone: 010-65105098

Affiliated State Key Laboratories: State Key Laboratory of Common Mechanism Research for Major Diseases

Technology field and major achievements: 

The group's research focuses on RNA metabolism and hematopoiesis. We analyzed the basic laws of stem cell fate transition, hematopoietic development and differentiation, and disease development from the perspective of RNA metabolism. We aimed to uncover novel functions of RNA, identify new mechanisms of RNA metabolism, explore new methods of disease treatment by interfering with RNA metabolism, and carry out RNA therapy.

In recent years, the group has made a number of important discoveries, and the work has been published in Cell Stem Cell, Developmental Cell, Blood, EMBO J (2015, 2020), Nature Communications, Genome Research, Stem Cell Reports and other academic journals. Additionally, the PI was awarded as The National Excellent Youth (2021), the Beijing 'Rising Star of Science and Technology' (2017), and the 'Concord Rising Star' (2015).

Main research findings:

1. RNA metabolism and hematopoietic regulation

We presented the long non-coding RNA (lncRNA) landscape of mouse HSC development at single-cell resolution and identified the key regulator lncRNA pivotal for the “endothelial-to-HSC” transition (Cell Stem Cell, 2019). The article was recommended by Faculty 1000. During the differentiation of HSPCs, we have provided the first delineation of RNA editome in the hematopoietic cascade combining RNA-sequencing and global genome DNA-sequencing analysis, and identified a key editable regulator that controls HSC differentiation (Blood, 2021). Performing comprehensive investigation of the expression characteristics of pseudogenes and their association with diseases, we find that one pseudogene-derived non-coding RNA HBBP1 evolved important role and novel mechanism to regulate human erythropoiesis and diseases (Developmental Cell, 2021).

2. RNA metabolism and stem cell fate

By elucidating the function of RBPs in the exit of embryonic stem cells from pluripotency, our findings indicate that hnRNPLL plays a pivotal role in this process through regulating RNA alternative splicing (EMBO J. 2021). We have identified a series of microRNAs that synergies with transcription factors to regulate hematopoietic stem cell and embryonic stem cell differentiation (EMBO J 2015). We have mapped the dynamics and patterns of RNA localization during differentiation of pluripotent stem cells to the mesoderm (Stem Cell Reports 2024). We also revealed the potential function of pseudogenes during early human embryonic development (J Genet Genomics 2024).

3. RNA metabolism and blood diseases

We have revealed the role of RNA metabolism in the development of leukemia and identified new potential therapeutic targets; established the RNA editing database REDH for normal blood cells and leukemia cells (Chin Med J 2024). We have found that the pseudogene HBBP1 could be involved in the promotion of increased fetal hemoglobin levels in patients with β-thalassemia by increasing TAL1 expression, and attenuated the symptoms of anemia in patients (Developmental Cell 2021).

Representativeness:

1. Mengyao Sun†, Le Chang†, Liu He, Li Wang, Zhengyang Jiang, Yanmin Si, Jia Yu, Yanni Ma*. Combining single-cell profiling and functional analysis explores the role of pseudogenes in human early embryonic development. J Genet Genomics. 2024 Jul 18:S1673-8527(24)00189-9.

2. Xu J†, He J†, Yang J†, Wang F, Huo Y, Guo Y, Si Y, Gao Y, Wang F, Cheng H, Cheng T, Yu J, Wang X, Ma Y*. REDH: A database of RNA editome in hematopoietic differentiation and malignancy. Chin Med J (Engl). 2024 Feb 5;137(3):283-293.

3. Zhou F†, Tan P†, Liu S, Chang L, Yang J, Sun M, Guo Y, Si Y, Wang D, Yu J, Ma Y*. Subcellular RNA distribution and its change during human embryonic stem cell differentiation. Stem Cell Reports. 2024 Jan 9;19(1):126-140.

4. Yanni Ma*, Zhongyang Chen, Jia Yu*. Pseudogenes and their potential functions in hematopoiesis. Experimental Hematology. 2021 Nov;103:24-29.

5. Fengjiao Wang†, Jiahuan He†, Siqi Liu†, Ai Gao, Liu Yang, Guohuan Sun, Wanqiu Ding, Chuanyun Li, Fanglin Gou, Manman He, Fang Wang, Xiaoshuang Wang, Xiangnan Zhao, Ping Zhu, Shao Hao, Yanni Ma*, Hui Cheng*, Jia Yu*, Tao Cheng*. Comprehensive RNA editome reveals edited Azin1 as a novel DDX1 partner to facilitate hematopoietic stem cell differentiation. Blood. 2021 Nov 18;138(20):1939-1952.

6. Yanni Ma†*, Siqi Liu†, Jie Gao†, Chunyan Chen†, Xin Zhang†, Hao Yuan, Zhongyang Chen, Xiaolin Yin, Chenguang Sun, Yanan Mao, Fanqi Zhou, Yi Shao, Qian Liu, Jiayue Xu, Li Cheng, Daqi Yu, Pingping Li, Ping Yi, Jiahuan He, Guangfeng Geng, Qing Guo, Yanmin Si, Hualu Zhao, Haipeng Li, Graham L Banes, He Liu, Yukio Nakamura, Ryo Kurita, Yue Huang, Xiaoshuang Wang, Fang Wang, Gang Fang, James Douglas Engel, Lihong Shi*, Yong E Zhang*, Jia Yu*. Genome-wide analysis of pseudogenes reveals HBBP1's human-specific essentiality in erythropoiesis and implication in β-thalassemia. Developmental Cell. 2021 Feb 22;56(4):478-493.e11.56(4):478–493.e11.

7. Xue Wang†, Changyun Ping†, Puwen Tan†, Chenguang Sun, Guang Liu, Tao Liu, Shuchun Yang, Yanmin Si, Lijun Zhao, Yongfei Hu, Yuyan Jia, Xiaoshuang Wang, Meili Zhang, Fang Wang, Dong Wang*, Jia Yu*, Yanni Ma*, Yue Huang*. hnRNPLL controls pluripotency exit of embryonic stem cells by modulating alternative splicing of Tbx3 and Bptf. The EMBO Journal. 2021 Feb 15. 40(4):e104729.

8. Kai Li†, Jiayue Xu†, Yanyun Luo†, Dingfeng Zou, Ruiqin Han, Shunshun Zhong, Qing Zhao, Xinyu Mang , Mengzhen Li, Yanmin Si , Yan Lu, Pengyu Li, Cheng Jin, Zhipeng Wang, Fang Wang, Shiying Miao, Bo Wen, Linfang Wang, Yanni Ma*, Jia Yu*, Wei Song*. Panoramic transcriptome analysis and functional screening of long noncoding RNAs in mouse spermatogenesis. Genome Research. 2021 Jan. 31(1):13-26.

9. Jie Zhou†, Jiayue Xu†, Lingling Zhang†, Siqi Liu†, Yanni Ma†, Xin Wen, Junkai Hao, Zongcheng Li, Yanli Ni, Xianlong Li, Fan Zhou, Qingqing Li, Fang Wang, Xiaoshuang Wang, Yanmin Si, Pengcheng Zhang, Chen Liu, Marisa Bartolomei, Fuchou Tang, Bing Liu*, Jia Yu*, Yu Lan*. Combined Single-Cell Profiling of lncRNAs and Functional Screening Reveals that H19 Is Pivotal for Embryonic Hematopoietic Stem Cell Development. Cell Stem Cell. 2019 Feb 7. 24(2):285-298.e5.

10. Yanni Ma†, Nan Yao†, Guang Liu†, Lei Dong, Fang Wang, Bin Wang, He Dong, Xueju Wei, Meili Zhang, Shaowei Ji, Yufang Liu, Junwu Zhang, Yangming Wang, Yue Huang*,Jia Yu*. Functional screen reveals essential roles of miR-27a/24 in differentiation of embryonic stem cell. The EMBO Journal. 2015 Feb 3. 34(3):361–378.

11. Yanni Ma†, Bin Wang†, Fengbing Jiang†, Dongsheng Wang†, Huiwen Liu, Yunmeng Yan, He Dong, Fang Wang, Bei Gong, Yong Zhu, Lei Dong, Haixin Yin, Zhongzu Zhang, Hualu Zhao, Zhikui Wu, Junwu Zhang, Jingguo Zhou, Jia Yu*. A Feedback Loop Consisting of MicroRNA 23a/27a and the Beta-Like Globin Suppressors KLF3 and SP1 Regulates Globin Gene Expression. Molecular and Cellular Biology.2013 Oct; 33(20):3994-4007.