Cochlear organoids reveal transcriptional programs of postnatal hair cell differentiation from supporting cells

被引：7

作者：

Kalra, Gurmannat ^{[1
,2
]}

Lenz, Daniell ^{[3
,4
]}

Abdul-Aziz, Dunia ^{[3
,4
]}

Hanna, Craig ^{[4
]}

Basu, Mahashweta ^{[1
]}

Herb, Brian R. ^{[1
]}

Colantuoni, Carlo ^{[1
]}

Milon, Beatrice ^{[5
]}

Saxena, Madhurima ^{[6
,7
]}

Shetty, Amol C. ^{[1
]}

Hertzano, Ronna ^{[11
]}

Shivdasani, Ramesh A. ^{[6
,7
,8
]}

Ament, Seth A. ^{[1
,5
,9
]}

Edge, Albert S. B. ^{[3
,4
,8
,10
]}

机构：

[1] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD USA

[2] Univ Maryland, Sch Med, Program Mol Med, Baltimore, MD USA

[3] Harvard Med Sch, Dept Otolaryngol, Boston, MA 02115 USA

[4] Massachusetts Eye & Ear, Eaton Peabody Lab, Boston, MA 02114 USA

[5] Univ Maryland, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Baltimore, MD USA

[6] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA

[7] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Dept Med Oncol, Boston, MA USA

[8] Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[9] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD USA

[10] Harvard Med Sch, Program Speech & Hearing Biosci & Technol, Boston, MA 02115 USA

[11] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA

来源：

CELL REPORTS | 2023年 / 42卷 / 11期

关键词：

PROGENITOR CELLS; STEM-CELLS; REGENERATION; INNER; EXPRESSION; GENERATION;

D O I：

10.1016/j.celrep.2023.113421

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

We explore the changes in chromatin accessibility and transcriptional programs for cochlear hair cell differentiation from postmitotic supporting cells using organoids from postnatal cochlea. The organoids contain cells with transcriptional signatures of differentiating vestibular and cochlear hair cells. Construction of trajectories identifies Lgr5+ cells as progenitors for hair cells, and the genomic data reveal gene regulatory networks leading to hair cells. We validate these networks, demonstrating dynamic changes both in expression and predicted binding sites of transcription factors (TFs) during organoid differentiation. We identify known regulators of hair cell development, Atoh1, Pou4f3, and Gfi1, and the analysis predicts the regulatory factors Tcf4, an E-protein and heterodimerization partner of Atoh1, and Ddit3, a CCAAT/enhancer-binding protein (C/EBP) that represses Hes1 and activates transcription of Wnt-signaling-related genes. Deciphering the signals for hair cell regeneration from mammalian cochlear supporting cells reveals candidates for hair cell (HC) regeneration, which is limited in the adult.

引用

页数：18

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