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Single-Cell Transcriptomics Reveals Chemotaxis-Mediated Intraorgan Crosstalk During Cardiogenesis.
Xiong, Haiqing; Luo, Yingjie; Yue, Yanzhu; Zhang, Jiejie; Ai, Shanshan; Li, Xin; Wang, Xuelian; Zhang, Yun-Long; Wei, Yusheng; Li, Hui-Hua; Hu, Xinli; Li, Cheng; He, Aibin.
Afiliação
  • Xiong H; From the Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine (H.X., Y.L., Y.Y., J.Z., S.A., X.L., X.W., X.H., A.H.), Peking University, China.
  • Luo Y; Peking-Tsinghua Center for Life Sciences (H.X., Y.L., A.H.), Peking University, China.
  • Yue Y; Academy for Advanced Interdisciplinary Studies (H.X., Y.L.), Peking University, China.
  • Zhang J; From the Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine (H.X., Y.L., Y.Y., J.Z., S.A., X.L., X.W., X.H., A.H.), Peking University, China.
  • Ai S; Peking-Tsinghua Center for Life Sciences (H.X., Y.L., A.H.), Peking University, China.
  • Li X; Academy for Advanced Interdisciplinary Studies (H.X., Y.L.), Peking University, China.
  • Wang X; From the Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine (H.X., Y.L., Y.Y., J.Z., S.A., X.L., X.W., X.H., A.H.), Peking University, China.
  • Zhang YL; From the Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine (H.X., Y.L., Y.Y., J.Z., S.A., X.L., X.W., X.H., A.H.), Peking University, China.
  • Wei Y; From the Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine (H.X., Y.L., Y.Y., J.Z., S.A., X.L., X.W., X.H., A.H.), Peking University, China.
  • Li HH; From the Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine (H.X., Y.L., Y.Y., J.Z., S.A., X.L., X.W., X.H., A.H.), Peking University, China.
  • Hu X; From the Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine (H.X., Y.L., Y.Y., J.Z., S.A., X.L., X.W., X.H., A.H.), Peking University, China.
  • Li C; Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, China (Y.-L.Z., H.-H.L.).
  • He A; School of Life Sciences (Y.W., C.L.), Peking University, China.
Circ Res ; 125(4): 398-410, 2019 08 02.
Article em En | MEDLINE | ID: mdl-31221018
ABSTRACT
RATIONALE We hypothesized that the differentiation processes of cardiac progenitor cell (CP) from first and second heart fields (FHF and SHF) may undergo the unique instructive gene regulatory networks or signaling pathways, and the precise SHF progression is contingent on the FHF signaling developmental cues.

OBJECTIVE:

We investigated how the intraorgan communications control sequential building of discrete anatomic regions of the heart at single-cell resolution. METHODS AND

RESULTS:

By single-cell transcriptomic analysis of Nkx2-5 (NK2 homeobox 5) and Isl1 (ISL LIM homeobox 1) lineages at embryonic day 7.75, embryonic day 8.25, embryonic day 8.75, and embryonic day 9.25, we present a panoramic view of distinct CP differentiation hierarchies. Computational identifications of FHF- and SHF-CP descendants revealed that SHF differentiation toward cardiomyocytes underwent numerous step-like transitions, whereas earlier FHF progressed toward cardiomyocytes in a wave-like manner. Importantly, single-cell pairing analysis demonstrated that SHF-CPs were attracted to and expanded FHF-populated heart tube region through interlineage communications mediated by the chemotactic guidance (MIF [macrophage migration inhibitory factor]-CXCR2 [C-X-C motif chemokine receptor 2]). This finding was verified by pharmacological blockade of this chemotaxis in embryos manifesting limited SHF cell migration and contribution to the growth of the outflow tract and right ventricle but undetectable effects on the left ventricle or heart tube initiation. Genetic loss-of-function assay of Cxcr2 showed that the expression domain of CXCR4 was expanded predominantly at SHF. Furthermore, double knockout of Cxcr2/Cxcr4 exhibited defective SHF development, corroborating the redundant function. Mechanistically, NKX2-5 directly bound the Cxcr2 and Cxcr4 genomic loci and activated their transcription in SHF.

CONCLUSIONS:

Collectively, we propose a model in which the chemotaxis-mediated intraorgan crosstalk spatiotemporally guides the successive process of positioning SHF-CP and promoting primary heart expansion and patterning upon FHF-derived heart tube initiation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article