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Stem Cell Reports · 2026 ·Vol. 21 ·期 9 · IF 5.6

Bone marrow-inspired DLL1-presenting microparticles enhance asymmetric division and maintenance of mouse hematopoietic stem and progenitor cells

Li Wenjing,Feng Yiting,Han Dongbo,Ao Yanxiao,Michael W. Chen,Li Ning,Jin Yuhong,Liang Haiwei,Liu Wen,Zhu Xiaoyu,Du Yanan

Understanding the regulation of hematopoietic stem and progenitor cell (HSPC) fate and translating it into effective culture strategies remains a significant challenge. Asymmetric lysosomal inheritance during HSPC division has been shown to predict variations in daughter cell activity and fate, yet the underlying regulators remain unclear. Through cell-cell communication analysis of bone marrow single-cell sequencing data, we identified the Notch ligand Delta-like protein 1 (DLL1) as a potential regulator in HSPC asymmetric division (ACD). Interactions between DLL1-presenting microparticles (MP-Ds) and HSPCs were observed in addressable microwell arrays, simulating cellular responses to localized niche signals. Long-term single-cell tracking revealed that MP-D interactions polarized HSPC lysosomes toward the contact site, directing division orientation and consequent asymmetric lysosomal inheritance in paired daughter cells. Furthermore, this co-culture system enhanced long-term hematopoietic reconstitution capacity of HSPCs in serial transplantations. Our findings support an association between HSPC ACD and the presentation mode of DLL1 signals, which enhances the ex vivo maintenance of HSPCs.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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POULTRY SCIENCE · 2020 · IF 2.659

Paneth cells mediated the response of intestinal stem cells at the early stage of intestinal inflammation in the chicken

Lingzi Yu,Xiaochen Xie,Keyang Jiang,Yi Hong,Zhou Zhou,Yuling Mi,Caiqiao Zhang,Jian Li

The rapid renewal and repair of the intestinal mucosa are based on intestinal stem cells ( ISC ), which are located at the crypt bottom. Paneth cells are an essential component in the crypt, which served as the niche for ISC development. However, in the chicken, how the function of Paneth cells changes during intestinal inflammation is unclear and is the key to understand the mechanism of mucosal repair. In the present study, 36 HyLine White chickens (7 d of age, n = 6) were randomly divided into 1 control and 5 lipopolysaccharide ( LPS ) injection groups. The chickens were injected (i.p.) with PBS in the control group, however, were injected (i.p.) with LPS (10 mg/kg BW) in the LPS injection groups, which would be sampled at 5 time points (1 h postinjection [ hpi ], 2 hpi, 4 hpi, 6 hpi, and 8 hpi). Results showed that tumor necrosis factor-α mRNA transcription in duodenal tissue increased gradually since 1 hpi, peaked at 4 hpi, and then reduced remarkably, indicating that 4 hpi of LPS was the early stage of intestinal inflammation. Meanwhile, the MUC2 expression in duodenal tissue was dramatically reduced since 1 hpi of LPS. The ISC marker, Lgr5 and Bmi1 , in the duodenal crypt were reduced from 1 hpi to 4 hpi and elevated later. Accordingly, the hydroethidine staining showed that the reactive oxygen species level, which drives the differentiation of ISC, in the duodenal crypt reduced obviously at 1 hpi and recovered gradually since 4 hpi. The analysis of Paneth cells showed that many swollen mitochondria appeared in Paneth cells at 4 hpi of LPS. Meanwhile, the Lysozyme transcription in the duodenal crypt was substantially decreased since 1 hpi of LPS. However, the Wnt3a and Dll1 in duodenal crypt decreased at 1 hpi of LPS, then increased gradually. In conclusion, Paneth cells were impaired at the early stage of intestinal inflammation, then recovered rapidly. Thus, the ISC activity was reduced at first and recovery soon.

研究领域: 免疫学 · 胃肠病学 · 动物科学 · 分子生物学
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APPLIED MICROBIOLOGY AND BIOTECHNOLOGY · 2021 ·Vol. 105 ·期 23 ·8823-8835 · IF 4.813

Lactobacillus salivarius and Lactobacillus agilis feeding regulates intestinal stem cells activity by modulating crypt niche in hens

Hong Yi,Zhou Zhou,Yu Lingzi,Jiang Keyang,Xia Jiamiao,Mi Yuling,Zhang Caiqiao,Li Jian

Previously, we found that Lactobacillus salivarius , Lactobacillus agilis , and Lactobacillus aviarius were associated with excellent egg nutrition in native chicken. Next, the optimal Lactobacillus combination is worth studying. Here, a total of 120 HyLine hens (30 hens per group contained 3 replicate cells, 10 hens/cell) in the laying peak period were randomly divided into (1) control, (2) L. salivarius  +  L. agilis , (3) L. salivarius  +  L. aviarius , and (4) L. agilis  +  L. aviarius groups, fed with diet only or with corresponding Lactobacilli (10 8 colony-forming units/hen/day) for 30 days. As a result, L. salivarius  +  L. agilis feeding could (1) improve egg-laying rate, egg weight, and albumen’s amino acid levels; (2) increase Lactobacillus abundance, decrease Escherichia coli abundance, upregulate the tryptophan metabolism pathway-related molecules, and downregulate the primary bile acid biosynthesis pathway-related molecules in intestinal contents; and (3) upregulate oxidative-phosphorylation pathway-related genes, reactive oxygen species levels, and mRNA abundance of Wnt3a , Dll1 , Lgr5 , CCDN1 , and CDK2 in the crypt. Collectively, L. salivarius  +  L. agilis feeding in hens could improve intestinal microflora and metabolism profile, promote crypt’s local energy metabolism and reactive oxygen species levels, and thus enhance Paneth cells and intestinal stem cells activity. Key points • Lactobacilli co-feeding could improve laying performance and egg nutrition. • Lactobacilli co-feeding could improve intestinal microflora and metabolism profile. • Lactobacilli co-feeding could enhance Paneth cells and intestinal stem cells activity.

研究领域: 动物科学 · 微生物学 · 营养学 · 分子生物学
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