Efficient Derivation of Purified Lung and Thyroid Progenitors from Embryonic Stem Cells

被引：297

作者：

Longmire, Tyler A. ^{[1
,4
,11
]}

Ikonomou, Laertis ^{[1
,4
,11
]}

Hawkins, Finn ^{[1
,4
,11
]}

Christodoulou, Constantina ^{[1
,4
,11
]}

Cao, Yuxia ^{[1
,4
,11
]}

Jean, J. C. ^{[1
,4
,11
]}

Kwok, Letty W. ^{[1
,4
,11
]}

Mou, Hongmei ^{[5
]}

Rajagopal, Jayaraj ^{[5
]}

Shen, Steven S. ^{[2
,3
,6
,7
,8
]}

Dowton, Anne A. ^{[1
,4
,11
]}

Serra, Maria ^{[1
,4
,11
]}

Weiss, Daniel J. ^{[9
]}

Green, Michael D. ^{[10
]}

Snoeck, Hans-Willem ^{[10
]}

Ramirez, Maria I. ^{[1
,4
,11
]}

Kotton, Darrell N. ^{[1
,4
,11
]}

机构：

[1] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA

[2] Boston Univ, Sch Med, Sect Computat Biomed, Boston, MA 02118 USA

[3] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA

[4] Boston Univ, Ctr Regenerat Med CReM, Boston, MA 02118 USA

[5] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA

[6] NYU, Sch Med, Ctr Hlth Informat & Bioinformat, New York, NY 10016 USA

[7] NYU, Sch Med, Dept Biochem, New York, NY 10016 USA

[8] NYU, Sch Med, Dept Med, New York, NY 10016 USA

[9] Univ Vermont, Coll Med, Vermont Lung Ctr, Burlington, VT 05405 USA

[10] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA

[11] Boston Med Ctr, Boston, MA 02118 USA

来源：

CELL STEM CELL | 2012年 / 10卷 / 04期

关键词：

DEFINITIVE ENDODERM; II CELLS; IPS CELLS; MOUSE; DIFFERENTIATION; EPITHELIUM; FOREGUT; PROTEIN; LIVER; MORPHOGENESIS;

D O I：

10.1016/j.stem.2012.01.019

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Two populations of Nicx2-1+ progenitors in the developing foregut endoderm give rise to the entire postnatal lung and thyroid epithelium, but little is known about these cells because they are difficult to isolate in a pure form. We demonstrate here the purification and directed differentiation of primordial lung and thyroid progenitors derived from mouse embryonic stem cells (ESCs). Inhibition of TGF beta and BMP signaling, followed by combinatorial stimulation of BMP and FGF signaling, can specify these cells efficiently from definitive endodermal precursors. When derived using Nkx2-1(GFP) knockin reporter ESCs, these progenitors can be purified for expansion in culture and have a transcriptome that overlaps with developing lung epithelium. Upon induction, they can express a broad repertoire of markers indicative of lung and thyroid lineages and can recellularize a 3D lung tissue scaffold. Thus, we have derived a pure population of progenitors able to recapitulate the developmental milestones of lung/thyroid development.

引用

页码：398 / 411

页数：14

共 57 条

[1] Derivation of type II alveolar epithelial cells from murine embryonic stem cells [J].