Spatial-Temporal Lineage Restrictions of Embryonic p63(+) Progenitors Establish Distinct Stem Cell Pools in Adult Airways.
Spatial-Temporal Lineage Restrictions of Embryonic p63(+) Progenitors Establish Distinct Stem Cell Pools in Adult Airways.
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DOI：
10.1016/j.devcel.2018.03.001
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发表时间：
2018-03-26
影响因子：
11.8
通讯作者：
Cardoso WV
中科院分区：
文献类型：
--
作者：
Yang Y;Riccio P;Schotsaert M;Mori M;Lu J;Lee DK;García-Sastre A;Xu J;Cardoso WV
基底细胞是皮肤、气管、食道和尿路中表达p63的多能性祖细胞。p63在发育中的气道中是丰富的，然而，胚胎p63+细胞如何促进发育和出生后呼吸道上皮，以及它们最终如何与成人bc相关联，仍不清楚。利用体内谱系追踪和功能方法，我们发现来自肺原基的p63+细胞最初是气道和肺泡谱系的多能祖细胞，但后来在近端受到限制，无法形成气管成体干细胞库。在肺内气道中，这些细胞在支气管中保持未成熟到成年，建立了一种罕见的p63+Krt5−祖细胞群，对H1N1病毒诱导的严重损伤有反应。有趣的是，这个库包括一个CC10谱系标记的p63+Krt5−细胞亚群，这是完全h1n1应答所必需的。这些数据阐明了在呼吸系统中建立区域不同的成体干细胞库的关键方面，可能与其他器官相关。Yang等人发现胚胎p63+细胞最初是气道和肺泡的多能祖细胞。然而，后来，它们被近端限制产生气管基底细胞和肺内p63+Krt5−祖细胞池，维持未成熟到成年。该细胞池包含p63+CC10Lineage+细胞，介导H1N1病毒诱导的病理性重构。
Basal cells (BCs) are p63-expressing multipotent progenitors of skin, tracheoesophageal and urinary tracts. p63 is abundant in developing airways, however, it remains largely unclear how embryonic p63+ cells contribute to the developing and postnatal respiratory tract epithelium, and ultimately how they relate to adult BCs. Using lineage-tracing and functional approaches in vivo, we show that p63+ cells arising from the lung primordium are initially multipotent progenitors of airway and alveolar lineages, but later become restricted proximally to generate the tracheal adult stem cell pool. In intrapulmonary airways these cells are maintained immature to adulthood in bronchi, establishing a rare p63+Krt5− progenitor cell population that responds to H1N1 virus-induced severe injury. Intriguingly, this pool includes a CC10 lineage-labeled p63+Krt5− cell subpopulation required for a full H1N1-response. These data elucidates key aspects in the establishment of regionally distinct adult stem cell pools in the respiratory system, potentially with relevance to other organs. Yang et al. show that embryonic p63+ cells are initially multipotent progenitors of airways and alveoli. Later, however, they become proximally restricted to generate tracheal basal cells and an intrapulmonary p63+Krt5− progenitor pool that is maintained immature to adulthood. This pool contains p63+CC10Lineage+ cells and mediates H1N1 virus-induced pathological remodeling.
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影响因子：
64.5
作者：
Kumar PA;Hu Y;Yamamoto Y;Hoe NB;Wei TS;Mu D;Sun Y;Joo LS;Dagher R;Zielonka EM;Wang de Y;Lim B;Chow VT;Crum CP;Xian W;McKeon F
通讯作者：
McKeon F
影响因子：
21.3
作者：
Xi Y;Kim T;Brumwell AN;Driver IH;Wei Y;Tan V;Jackson JR;Xu J;Lee DK;Gotts JE;Matthay MA;Shannon JM;Chapman HA;Vaughan AE
通讯作者：
Vaughan AE
影响因子：
4.6
作者：
Rawlins, Emma L.;Clark, Cheryl P.;Hogan, Brigid L. M.
通讯作者：
Hogan, Brigid L. M.
p63（+）KRT5（+）远端气道干细胞对于肺部再生至关重要。
影响因子：
64.8
作者：
Zuo W;Zhang T;Wu DZ;Guan SP;Liew AA;Yamamoto Y;Wang X;Lim SJ;Vincent M;Lessard M;Crum CP;Xian W;McKeon F
通讯作者：
McKeon F
影响因子：
5.9
作者：
Ray, Samriddha;Chiba, Norika;Yao, Changfu;Guan, Xiangrong;McConnell, Alicia M.;Brockway, Brian;Que, Loretta;McQualter, Jonathan L.;Stripp, Barry R.
通讯作者：
Stripp, Barry R.