出生后小鼠心肌组织生长发育的转录组分析

doi:10.16288/j.yczz.24-328

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Hereditas(Beijing) ›› 2025, Vol. 47 ›› Issue (10): 1132-1145.doi: 10.16288/j.yczz.24-328

• Research Article • Previous Articles Next Articles

Transcriptome analysis of postnatal mouse cardiac tissue growth and development

Xiaocong Zhu¹(), Shengnan Wang²(), Lin Jiang², Shuqin Liu¹()

1. College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, China
2. Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China

Received:2024-11-13 Revised:2025-02-15 Online:2025-10-20 Published:2025-04-21
Contact: Shuqin Liu E-mail:2975029339@qq.com;namowsn@hotmail.com;sqliu12@qau.edu.cn
Supported by:
Donkey Innovation Team of Shandong Modern Agricultural Industry Technology System(SDAIT-27)

Abstract

Abstract:

Postnatal cardiac function in mammals is closely associated with cardiomyocyte proliferation and hypertrophy. However, the molecular mechanisms regulating cardiomyocyte proliferation and hypertrophy have not yet been fully elucidated. Therefore, phenotypic measurements and transcriptomic sequencing were performed on myocardial tissues from 7-day-old (P7) and 3-month-old (3m) female C57BL/6 mice to investigate changes in cardiomyocytes during growth and development and to identify key genes regulating myocardial growth and development. In comparison to 7-day-old mice, 3-month-old mice exhibited a significant increase in heart weight (P<0.001) and the cross-sectional area of cardiomyocytes (P<0.001). Transcriptome sequencing identified 3,858 differentially expressed genes (DEGs), including 2,021 up-regulated and 1,837 down-regulated genes. Gene Ontology (GO) functional annotation analysis demonstrated that the differentially expressed genes were significantly enriched in biological processes including cell cycle, cell division, cardiac morphogenesis and cellular proliferation. Significantly enriched KEGG pathways were identified, including those for DNA replication, ECM-receptor interaction, the cell cycle, metabolic pathways, and other signaling pathways. Furthermore, key candidate genes associated with myocardial tissue growth and development in mice, including Hey2, Foxm1, Igf1, Xirp2, Sfrp2, Egf, Fgfr2, Tbx20, Fgf1 and Igf2 were identified through screening. qRT-PCR validation results demonstrated that the expression trends of the 10 candidate genes related to myocardial growth and development were consistent with the RNA-seq results, confirming the reliability of the sequencing data. The findings of this study provide new insights into the molecular mechanisms underlying the growth and development of mouse myocardial tissue.

Key words: mice, myocardial tissue, growth and development, RNA-seq

Xiaocong Zhu, Shengnan Wang, Lin Jiang, Shuqin Liu. Transcriptome analysis of postnatal mouse cardiac tissue growth and development[J]. Hereditas(Beijing), 2025, 47(10): 1132-1145.

Figures/Tables 13

Table 1

Fig. 1

Fig. 2

Table 2

Table 3

Fig. 3

Fig. 4

Supplementary Table 1

Supplementary Table 2

GO terms related to heart development, organ development, and cell proliferation"

编号	条目	数量	P值	基因
GO:0008284	positive regulation of cell population proliferation	104	1.22E-06	Cdc20，Slc25a33，Hmgcr，Tff2，Crlf1，Has2，Cdk2，Efemp1，Ptn，Nanog，Folr2，Itgax，Tgfb2，Prc1，Rtkn2，Nrg4，Ets1，Tipin，Optn，Igf1，Sapcd2，Edn3，Agtr2，Cdk4，Sinhcaf，Acta2，Reg3g，Ccn2，Sfrp2，Bmp2Cntfr，Kif14，Dot1l，Cldn5，Id4，Pdgfa，Adrb2，Thrb，Flt3l，Fgf1，Aldh1a2，S100a1，Acer2，Lgals3，Cck，Ptgfr，Sox4，Mzb1，Prdx3，Ar，Sox9，Ptgs2，Mapk15，Pitx2，Il7r，Clec7a，Prlr，Csf1r，Akr1cl，Il6st，Apln，Cav3，Bst1，Epcam，Il15，Chp2，Cxcr3，Kit，Fn1，Epha4，Egf，Aqp11，Fgf7，Lamc2，Clu，Foxm1，Hif1a，Ctsh，Prkcz，Tnc，Ccdc117，Cdca7l，Cnot6，Osmr，Rad51b，Enpp2，Fgfr2，Csf1，Cx3cl1，Hmga2，Mlxipl，Cdc7，Igf2，Kif20b，Crh，Tnfsf13，Aif1，Ezh2，Marcksl1，Hipk2，Il6ra，Fbxo5，Hpse2，Fgf2
GO:0042127	regulation of cell population proliferation	36	3.93E-04	Ccdc88a，Ptgs2，Prg4，Osgin1，Dnmt1，Pf4，Pitx2，Sfrp2，Cxcl9，Junb，Gli3，Bcl6，Nr3c2，Sparc，Ptgs1，Serpine1，Tgfb2，Chek1，Emilin2，Cebpa，Emilin1，Sqle，Igf1，Nr5a2，Mzb1，Ezh2，Nfkbia，Clu，Bex4，Foxm1，Fas，Stat2，Txnip，Sox9，Hif1a，Cdca7
GO:0008283	immune effecell population proliferationctor process	50	0.001055872	Gdf11，Fam83d，Tff2，Csf1r，Prok1，Gli3，H3f3b，Rasgrp4，Kit，Glul，Ddr1，Egf，Igf1，Brca2，Hoxa3，Edn3，Foxm1，Mycn，Tacc2，Map7，Mcm7，St8sia1，Bmp7，Mcm10，Pax3，H19，Tlx1，Id4，Ptges，Pdgfa，Fgfr2，Bcl6，Aldh1a2，Tacc3，Hmga2，Il18，Cebpa，Cdkn2c，Flt3，Marcksl1，Hipk2，Atad5，Zbtb16，Sox9，Melk，Hpse2，Tbx20，Fgf2，Drd2，Mki67
GO:0009888	tissue development	12	0.013249089	Postn，Lamb1，Dhcr24，Lncpint，Lamc1，Lamc3，Lama4，Nr5a2，Gaa，Pax3，Ntng2，Lamc2
GO:0007507	heart development	46	0.015057548	Tgfb1i1，Odad2，Casp7，Pitx2，Col3a1，Bmp2，Ppara，Dnai1，Pax3，Robo1，Ptk7，Mb，Adamts6，Acan，Vcan，Myh10，Gli3，Mical2，Lox，Dnaaf3，Wt1，Frem2，Aldh1a2，Pdlim3，Gjc1，Adap2，Stra6，Hey2，Tgfb2，Mmp13，Tfdp2，Pde2a，Fn1，Sox4，Gja6，Pcna，Osr1，Fbn1，Sh3pxd2b，Aplnr，Prickle4，Sox9，Casp3，Col6a1，Mmp9，Adam19
GO:0009887	animal organ morphogenesis	26	0.018261344	Gdf11，Pitx2，Bmp2，Lamc3，Bmp7，Palb2，Asxl3，Pdgfa，Thrb，Fgfr2，Fgf1，Foxf2，Lama4，Ntng2，Gpc3，Wnt11，Igf2，Lamc1，Wnt5b，Fgf7，Hoxa3，Nkx2-1，Lamc2，Lamb1，Tcf21，Fgf2
GO:0061061	muscle structure development	6	0.024757703	Tgfb1i1，Prickle4，Ark2c，Col6a1，Hoxa2，Pdlim3
	cardiac muscle tissue morphogenesis	6	0.024757703	Gm1322，Angpt1，Bmp2，Egln1，Tbx20，Tcap
GO:0048513	animal organ development	10	0.028652571	Kit，Fmr1，Nrg2，Dand5，Flt1，Rai2，Pax3，Spry2，Csf1r，Tlx1
GO:0060045	positive regulation of cardiac muscle cell proliferation	8	0.029630822	Ccnb1，Fgfr2，Ncam1，Pim1，Fgf2，Tbx20，Hey2，Cdk1

Supplementary Table 2

Supplementary Table 3

Supplementary Table 4

Supplementary Table 5

KEGG pathway enrichment analysis of DEGs"

编号	条目	数量	P值	基因
mmu04110	Cell cycle	55	1.10728E-10	Cdc20，E2f1，Cdc25b，Bub1，Orc1，Mcm2，Cdk2，Mad2l1，Mtbp，Ccnb1，Plk1，Skp2，Tgfb2，Cdk1，Chek1，Ccne2，Esco2，Rbl1，Mcm6，Ndc80，Smc1b，Mcm4，Knl1，Gadd45a，Aurkb，E2f2，Cdc45，Pttg1，Cdk4，Ticrr，Ttk，Rbl2，Cdc6，Mcm7，Ccna1，Mcm3，Dbf4，Espl1，Ccna2，Cdc25c，Bub1b，Orc6，Tfdp2，Cdt1，Cdc7，Cdca5，Pcna，Cdkn2c，Ccne1，Mcm5，Sgo1，Fbxo5，Trip13，Pkmyt1，Ccnb2
mmu04512	ECM-receptor interaction	36	3.9968E-09	Thbs2，Lamc2，Chad，Lamb1，Col6a1，Comp，Col4a2，Col4a1，Itga2
mmu04514	Cell adhesion molecules	56	8.23526E-09	H2-Aa，Cldn3，H2-Ab1，Lrrc4b，H2-T24，Icam1，Mag，Itgb7，Selp，Sele，H2-Ob，Cldn5，Cd34，Cd274，Vcan，Tigit，Cd86，Nrxn3，Ctla4，Cd28，Sdc1，H2-Eb1，Cadm3，Madcam1，Slitrk4，Cldn15，H2-T23，H2-DMb1，Cldn11
mmu03030	DNA replication	19	3.47378E-07	Mcm7，Rfc3，Prim1，Pcna，Mcm3，Rfc5，Prim2，Rfc4，Lig1，Mcm6，Mcm2，Mcm4，Mcm5，Fen1，Pola2，Pole2，Rnaseh2b，Dna2，Pole
mmu01100	Metabolic pathways	296	1.56801E-06	Dnmt1，Inpp5a，Lpin3，Hmgcr，Chsy3，Hddc2，St3gal5，Mtr，Cyp2e1，Adk，Selenbp1，Fmo1，Hsd11b1，Plcb2，Hpse，Bcat2，Gdpd3，Ptgs1，Cth，Phgdh，P4ha1，Echs1，Chpt1，Lalba，Nampt，Aldh4a1，Nat1，Ftcd，Acsl6，Ogdh，Hk2，Fmo2，E030003E18Rik，Cyp1a1，Nt5e，Abat，Hmgcs2，Oxct1，Ptgds，Bckdha，Sephs1，Tk1，Aldoc，Gaa，Dot1l，Pla2g12a，ND4L，Cpox，Scp2，Aoc1，Mpst，Aox3，St3gal6，Pomgnt2，Entpd2，Aldh1a2，Pdxk，Mocos，Nsd2，Aoc3，Papss1，Gda，Dck，Dctd，Nos1，Pfkm，Scd3，Tbxas1，Tpo，Scd2，Cyp26b1，Ehhadh，Extl1，Mccc2，Tha1，Me1，Ak9，Gsta13，Pfkfb1，Ptgs2，Hadhb，Ivd，Acss1，B4galt2，Scd4，COX3，Xdh，ATP6，Agpat2，Pdxp，Aldob，B3gnt5，Entpd5，COX1，Cyp26a1，Aldh6a1，COX2，Pla2g5，Ldhd，Ogdhl，P4ha3，Dgat2，Bst1，Gcdh，Acadsb，Pde2a，Glul，Pycr1，Auh，Lct，Pde6g，ND5，Gpld1，Alox5，St3gal3，Gstk1，Amd2，Gpam，Acot3，ND3，Hacd1，Tecr，Galnt15，Rrm1，Pnmt，Gpt2，Acsm5，Gsta1，Gstm1，St8sia1，Rimklb，Car5b，Mogat2，Fmo5，Alpl，Chac1，Ak4，Pde11a，Enpp2，Dpys，Gpt，Dhtkd1，Carnmt1，CYTB，Gsta3，Ethe1，Gstt2，Pld4，Gadl1，Khk，Pla2g2c，Cda，Cyp3a13，Lpin1，Cbs，Inmt，Gpx4，Hpse2，Nmnat3，Aspdh，Adcy9，Ddc，Gstt1，Mgat5b，Gstt3，Hk3，Gck，Nmrk2，Nqo1，L2hgdh，Xylt2，Suv39h1，Adi1，Cox6a2，Gsto2，Nnmt，Sqle，Gsto1，Pcx，Dbt，Kyat3，Cmbl，Asrgl1，Suox，Nmnat2，Tyms，Pipox，Pnpla2，Gnmt，Atp6v0e2，Dhfr，Cox6b2，Got1，Ahcyl2，Aldh1l1，Bckdhb，Amd1，Amy1，Psat1，Dnmt3b，Galnt16，Pafah1b3，Pnpla3，Hibadh，Rimkla，A4galt，Ptges，Dcxr，Dgkk，Pcca，Impa2，Gstm2，Gbgt1，Galnt5，Acer2，Gale，ND2，Elovl2，Mthfd1l，Sord，Aldh3b3，Inpp4b，Gsta2，Pde4c，Pank1，Acsl3，Pygb，Chsy1，Sds，Cyp2s1，Ggct，Ndst3，Maob，Hsd17b1，Nudt12，Acp5，Dhdh，Prodh，Galm，Chac2，Gpx3，Acot1，Pygm，Nt5c1a，Adh1，Mgst1，Kmt5c，P4ha2，Dglucy，Pcbd1，Ezh1，Chpf2，Aox1，Aspa，Mmut，Ckmt2，Acox1，Bdh1，Synj2，B3galt2，Pde7a，Aass，Mmab，Aldh2，Lrat，Dhcr24，Cds1，Mgat3，Cox6a1，Gstm7，Hnmt，Scd1，Acsbg3，Galk1，Pla2g7，Sqor，Rrm2，Upp1，Car15，Cyp27a1，Sardh，Pde4a，Gpx7，Suclg2，Ezh2，Adcy8，Pla2g2d，Ak7，Mgam，Ugt1a7c，Mccc1，Gstp2，Aldh1b1，Cox7a1，Gcat，ENSMUSG00000101904
mmu04974	Protein digestion and absorption	35	3.16384E-06	Col9a3，Eln，Col25a1，Col4a5，Col5a2，Col3a1，Col6a6，Col9a1，Col6a2，Col26a1，Slc36a2，Col9a2，Col1a1，Cpa2，Col27a1，Col8a1，Ace2，Col20a1，Col1a2，Col24a1，Prcp，Col12a1，Fxyd2，Col14a1，Atp1a2，Col18a1，Col11a1，Slc1a1，Col5a1，Col6a1，Col16a1，Kcne3，Col4a2，Cpa1，Col4a1
mmu04820	Cytoskeleton in muscle cells	60	3.34597E-06	Col3a1，Csrp2，Col9a2，Col1a1，Des，Sgca，Col27a1，Myh10，Tmod4，Sdc4，Pdlim3，Col1a2，Fn1，Myh8，Atp1a2，Fbn1，Fbln1，Col11a1，Thbs2，Col5a1，Myh14，Col6a1，Col4a2，Col4a1，Itgb7，Ankrd2，Thbs3，Col6a6，Col9a1，Diaph3，Csrp1，Col6a2，Myoz1，Itgb3，Vcan，Trim54，Col24a1，Lmod2，Sntb1，Myl9，Myot，Lmnb1，Gm1322，Actg2，Myoz2，Itgb6，Sdc1，Tcap，Fbn2，Sgcd，Tnni1，Comp，Nid2，Itga2
mmu00280	Valine, leucine and isoleucine degradation	23	4.45307E-06	Hadhb，Aldh2，Ivd，Bckdhb，Abat，Oxct1，Hmgcs2，Echs1，Auh，Bckdha，Dbt，Hibadh，Aox1，Mmut，Ehhadh，Pcca，Aldh6a1，Aox3，Mccc2，Mccc1，Bcat2，Aldh1b1，Acadsb
mmu04814	Motor proteins	52	1.04222E-05	Kif15，Dnai2，Tuba4a，Myo7b，Myo1f，Dnai1，Dynlt1a，Kifc5b，Kif1c，Dnah12，Myh10，Myh8，Tuba1b，Tubb6，Dynlt1f，Dnah10，Myh14，Kif20a，Kif18b，Acta2，Dnah6，Tuba8，Kif11，Dnah9，Myo7a，Kifc1，Kif26a，Kif27，Kif18a，Dynlt1b，Kif14，Tubb4a，Tubb2b，Tubb5，Kif21a，Myo3b，Tube1，Kif23，Myl9，Kif7，Kif26b，Kif2c，Kif20b，Actg2，Cenpe，Kif24，Myo5b，Tnni1，Dnai3，Tuba1a，Kif4，Kif22
mmu04610	Complement and coagulation cascades	30	2.53205E-05	Bdkrb2，C1qb，C3，C6，Itgb2，Cfh，Vsig4，C4b，Serpina1b，Serpina1d，Cfd，Plat，Itgax，C1s1，Serpina1e，Serpine1，Itgam，C1qa，F7，C5ar1，C7，C1ra，Vwf，Serping1，C3ar1，Clu，Cd59b，F2rl3，F13a1，C1qc

Supplementary Table 5

Fig. 5

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基因名称	引物序列 (5′→3′)
β-actin	F：AACCGTGAAAAGATGACCCAGAT
β-actin	R：CACAGCCTGGATGGCTACGT
18S rRNA	F：TTTCTCGATTCCGTGGGTGG
18S rRNA	R：TCAATCTCGGGTGGCTGAAC
Hey2	F：GAACAATTACCCTGGGCACG
Hey2	R：TTCGATCCCGACGCCTTTTT
Foxm1	F：CAGGAGAGCTATGCTGGTGGT
Foxm1	R：AGGGTGGCCTCTCAGACACA
Igf1	F：ATGACCGCACCTGCAATAAAG
Igf1	R：GAATGCTGGAGCCATAGCCT
Xirp2	F：GCAGCTTCTCGGCTAATGTCA
Xirp2	R：AGGCGTTGCAGGTTGAAGTA
Sfrp2	F：ATGAGACCATCCAGCCGTG
Sfrp2	R：CACACCTTGGGAGCTTCCTCT
Egf	F：GAGGTCCGCTAGAGAAATGTCA
Egf	R：TGGGGCATGTGCAGTGATAG
Fgfr2	F：TGCCGAATGAAGACCACGAC
Fgfr2	R：ACTCGGCCGAAACCTGTCT
Tbx20	F：GTCACAGCCTACCAGAACCAA
Tbx20	R：TTCTTCAAAGGTCCCCTCTCAAT
Fgf1	F：AAAGTGCGGGCGAAGTGTAT
Fgf1	R：CTCATTTGGTGTCTGCGAGC
Igf2	F：CGTGGCATCGTGGAAGAGT
Igf2	R：ACACGTCCCTCTCGGACTTG

样本	原始读数	质控后读数	质控率	Q30数据
9-2	74,869,328	71,669,772	95.72647961	94.88525
9-3	74,658,358	71,561,222	95.85158838	95.0681
9-5	78,257,522	74,637,762	95.37455326	94.8927
74	68,532,670	65,120,508	95.02111621	93.34445
48	79,189,892	76,434,652	96.52071757	94.78125
C62	76,870,844	73,976,702	96.2350589	94.4907
C63	81,374,030	76,251,440	93.70488349	94.839

样本	比对率(%)
9-2	93.09
9-3	93.56
9-5	93.44
74	90.83
48	90.08
C62	93.27
C63	92.78

类别	GO编号	条目	数量	P值
BP	GO:0007049	cell cycle	182	4.06083E-37
BP	GO:0051301	cell division	122	6.85875E-28
BP	GO:0002376	immune system process	141	2.25781E-24
BP	GO:0045087	innate immune response	138	9.96141E-24
BP	GO:0007059	chromosome segregation	51	1.28172E-20
BP	GO:0007155	cell adhesion	137	2.13134E-18
BP	GO:0030198	extracellular matrix organization	62	1.79199E-17
BP	GO:0006954	inflammatory response	100	3.63941E-16
BP	GO:0035458	cellular response to interferon-beta	35	1.72508E-15
BP	GO:0006260	DNA replication	44	7.87367E-15
CC	GO:0005737	cytoplasm	1148	1.94244E-56
CC	GO:0005576	extracellular region	397	1.46384E-45
CC	GO:0016020	membrane	1195	2.89258E-32
CC	GO:0062023	collagen-containing extracellular matrix	111	5.69624E-28
CC	GO:0031012	extracellular matrix	100	5.86897E-27
CC	GO:0005615	extracellular space	367	6.9155E-27
CC	GO:0009986	cell surface	186	3.62299E-25
CC	GO:0005856	cytoskeleton	275	6.68013E-25
CC	GO:0009897	external side of plasma membrane	145	1.86746E-23
CC	GO:0005634	nucleus	897	3.78546E-20
MF	GO:0005515	protein binding	876	8.00395E-46
MF	GO:0042802	identical protein binding	384	5.92756E-32
MF	GO:0046872	metal ion binding	588	3.67755E-26
MF	GO:0000166	nucleotide binding	310	1.38173E-22
MF	GO:0005524	ATP binding	278	6.55811E-21
MF	GO:0016491	oxidoreductase activity	141	2.05444E-20
MF	GO:0016787	hydrolase activity	272	1.38026E-15
MF	GO:0008017	microtubule binding	74	4.33152E-14
MF	GO:0005509	calcium ion binding	144	6.90979E-14
MF	GO:0042803	protein homodimerization activity	156	8.56528E-13

编号	条目	数量	P值	基因
GO:0008016	regulationofheartcontraction	7	0.002745762	Dmpk，Thrb，Kcnd2，S100a1，Hrc，Chrm2，Kcnd3
GO:0060452	positiveregulationofcardiacmusclecontraction	4	0.014216607	Adra1a，Ucn，Ace2，Ccn2
mmu04260	Cardiacmusclecontraction	14	0.028156635	Fxyd2，Atp1a2，COX3，Cacna2d1，Atp2a2，Cacna2d3，COX1，Cacna1s，CYTB，COX2，Hrc，Cox7a1，Atp2a1，Cox6a2

Transcriptome analysis of postnatal mouse cardiac tissue growth and development

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Figures/Tables 13

References 76

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编号	条目	数量	P值	基因
GO:0007507	heart development	33	1.03E-04	Odad2，Casp7，Pitx2，Col3a1，Bmp2，Ptk7，Robo1，Adamts6，Vcan，Acan，Myh10，Gli3，Mical2，Lox，Wt1，Frem2，Aldh1a2，Pdlim3，Gjc1，Hey2，Tgfb2，Fn1，Sox4，Pcna，Osr1，Fbn1，Sh3pxd2b，Aplnr，Sox9，Casp3，Col6a1，Tbx20，Adam19
GO:0060045	positive regulation of cardiac muscle cell proliferation	7	0.002951524	Ccnb1，Fgfr2，Ncam1，Pim1，Tbx20，Hey2，Cdk1
GO:0055015	ventricular cardiac muscle cell development	4	0.010869872	Myh10，Pitx2，Hey2，Cdk1
GO:0010659	cardiac muscle cell apoptotic process	5	0.01482361	Dynlt1f，Sfrp2，Dynlt1b，Hey2，Dynlt1a
GO:0060038	cardiac muscle cell proliferation	6	0.02682176	Fgfr2，Myh10，Tenm4，2810429I04Rik，Hey2，Tgfb2

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