Identification of Lgr5-Independent Spheroid-Generating Progenitors of the Mouse Fetal Intestinal Epithelium

被引：204

作者：

Mustata, Roxana C. ^{[1
]}

Vasile, Gabriela ^{[1
]}

Fernandez-Vallone, Valeria ^{[1
]}

Strollo, Sandra ^{[1
]}

Lefort, Anne ^{[1
]}

Libert, Frederick ^{[1
]}

Monteyne, Daniel ^{[2
]}

Perez-Morga, David ^{[2
,3
]}

Vassart, Gilbert ^{[1
]}

Garcia, Marie-Isabelle ^{[1
]}

机构：

[1] ULB, Fac Med, IRIBHM, B-1070 Brussels, Belgium

[2] Univ Libre Brussels, IBMM, Lab Mol Parasitol, B-6041 Gosselies, Belgium

[3] Univ Libre Brussels, CMMI, B-6041 Gosselies, Belgium

来源：

CELL REPORTS | 2013年 / 5卷 / 02期

关键词：

PANETH CELL-DIFFERENTIATION; STEM-CELL; LGR5; MICE; EXPRESSION; WNT; MORPHOGENESIS; POPULATIONS; HOMEOSTASIS; SIGNATURE;

D O I：

10.1016/j.celrep.2013.09.005

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Immortal spheroids were generated from fetal mouse intestine using the culture system initially developed to culture organoids from adult intestinal epithelium. Spheroid proportion progressively decreases from fetal to postnatal period, with a corresponding increase in production of organoids. Like organoids, spheroids show Wnt-dependent indefinite self-renewing properties but display a poorly differentiated phenotype reminiscent of incompletely caudalized progenitors. The spheroid transcriptome is strikingly different from that of adult intestinal stem cells, with minimal overlap of Wnt target gene expression. The receptor LGR4, but not LGR5, is essential for their growth. Trop2/Tacstd2 and Cnx43/Gja1, two markers highly enriched in spheroids, are expressed throughout the embryonic-day-14 intestinal epithelium. Comparison of in utero and neonatal lineage tracing using Cnx43-CreER and Lgr5-CreERT2 mice identified spheroidgenerating cells as developmental progenitors involved in generation of the prenatal intestinal epithelium. Ex vivo, spheroid cells have the potential to differentiate into organoids, qualifying as a fetal type of intestinal stem cell.

引用

页码：421 / 432

页数：12

共 51 条

[1] Gap junction development in the human fetal hair follicle and bulge region [J].